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A Review of the Botany, Traditional Use, Phytochemistry, Analytical Methods, Pharmacological Effects, and Toxicity of Angelicae Pubescentis Radix.

1. Introduction

Angelicae Pubescentis Radix (AP) is derived from the dry root of Angelica pubescens Maxim f. biserrata Shan et Yuan, a plant in the Apiaceae family. AP was first published in ShengNong's herbal classic, which is spicy, bitter, and mild in nature and enters the kidney meridian and bladder meridian exerting the remedial effect [1]. AP was recorded and summarized by each edition of the Chinese Pharmacopoeia, with the functions of removing wind and dehumidification, relieving pain in paralysis, and so on. AP was often used to treat rheumatism and headaches caused by dampness and cold [2].

A phytochemical study shows that the main active components of AP include volatile oil, coumarin, organic acids, terpenes, polysaccharides, sterols, and other compounds. And, the pharmacological studies show that AP has anti-inflammatory, antirheumatic, sedative, hypnotic, neuroprotective, antioxidant, antitumor, antiallergic, and other effects, which may be closely related to its complex chemical components [3-10]. In clinical application, AP is often used in combination with other TCMs, which has the functions of dispelling wind and dehumidification, promoting blood circulation and relieving pain, relaxing muscles and activating collaterals, tonifying the liver and kidney, and strengthening tendons and bones [11-15], such as Duhuo-Jisheng Wan, Tianhe Zhuifeng Gao, and Tianma Wan. It is usually used to treat arthritis, lumbago, and cephalgia caused by cold and dampness, blocking collaterals of blood stasis, and deficiency of qi and blood [16-18].

AP, as a famous TCM, has been widely used in China for thousands of years. However, there was no in-depth study on the material basis, target, and mechanism of action of AP. There was no optimal processing technique for AP. And, at present, the toxic components and the related mechanism also have not been clarified. In this study, a total of 551 articles were identified from the database in this study, most of which were excluded due to no mention of botany, traditional use, phytochemistry, pharmacological effects of AP, or duplication. 129 references are included in this review. Compared with other reviews, this study provides a more comprehensive overview of botany, traditional uses, phytochemistry, pharmacological effects, and toxicology, with additional reviews of analytical methods, quality control, and processing. It also emphasizes its possible future development direction, which lays a foundation for a comprehensive understanding of AP, further research and development of new drugs, and expansion of its application in clinical and world markets.

2. Botany

The Chinese Pharmacopoeia (2015 edition) records AP derived from the dry root of Angelica pubescens Maxim, f. biserrata Shan et Yuan. In early spring, when the seedlings are just germinating, or in late autumn, when the stems and leaves are withered, the soil is digged, the fibrous roots and sediments are removed, and then the roots are baked to half dry, piled up for 2 to 3 days, putting to soft and then baking to dry. DH is mainly distributed in Sichuan and Hubei provinces of China [2]. Native plants grow on the dank hillside, grass, or sparse thickets, like in a cool and humid climate, and are cold resistant, and most native plants grow in the altitude of 1200~2000 meters of the cold highland area. The plant is suitable to grow in fertile, loose alkaline soil, yellow sand soil, or black oil soil but not suitable to grow in the shallow soil, water, and clay soil [19]. There are a variety of invention patents for AP cultivation, planting, and harvesting methods, such as an AP cultivation method (CN. 201911138333) [20], an AP cultivation greenhouse (CN. 201811562359) [21], a method for cultivating high-quality AP (CN. 201810917290) [22], an AP cultivation method for high quality and high yield (CN. 201811053800), and also [23].

The roots of AP are thick and short, slightly cylindrical, 1.5-4 cm in length, and 1.5-3.5 cm in diameter. The lower roots have several curved branches, 12-30 cm in length, and 0.5-1.5 cm in diameter. The root surface is rough, gray-brown, with irregular longitudinal wrinkles and transverse cracks, and has many transverse long lenticels and fine roots [24]. The root head has a ring stripe and polytropic ring petiole mark, and the hollow stem mark is in the middle. Texture is hard, cross section is sallow white, and the cambium is ring brown. The leather part has a brown oil point (tubing), and the wood part is yellow brown. The transverse section of the root has a large curved section and oil spots. AP has a special flavor. It tastes bitter and hot and even can make a tongue numb. AP with thick, oily, and strong aroma are for the best [25].

3. Traditional Applications

Sheng Nong's herbal classic (Han dynasty, 947-950) records that AP can treat diseases caused by wind and cold, pain caused by bumping of knife wounds, epilepsy, female uterine fibroid hernia, etc. It is recorded in the Supplementary Records of Famous Physicians (the end of Han dynasty, 947-950) that AP can cure all kinds of limb joint pain caused by wind and evil spirits, whether it is a new disease or a long illness. Medicinal Theory (Tang dynasty, 923-936) records that AP can treat the pain caused by wind, cold and wet, qi disorder, itchy skin, pain caused by limb spasm, pain caused by fatigue, and tooth pain. According to Medical Origins (Jin dynasty, 1186), AP can remove moisture and treat headaches and dizziness. Wang Haogu (Yuan dynasty, 1271-1368) shows that AP could cure the pain in the waist and leg. According to the book "Yeyan" (Ming dynasty, 1368-1644), AP can be used for sweating, treatment of flank pain, and head and facial pain. Bencao Tongxuan (Ming dynasty, 1368-1644) records that AP is used for the treatment of speechlessness, stiff hands and feet, mouth and eyes skewness, swollen eyes, and skin itching. Bencaozheng (Ming dynasty, 1368-1644) records that AP can cure rheumatism, foot pain, itching, and stiff limbs. According to Modern Practical Chinese Medicine, AP can induce sweating, promote urine discharge, and eliminate edema.

Clinically, AP is often used in combination with other TCMs. The dried root of the TCMs commonly used in combination with AP are as follows:

(1) AP compatibility with Paeoniae Radix Alba, which has the functions of tonifying liver and dispelling wind [11].

(2) AP compatibility with Dictamni Cortex, which has the functions of dispelling wind and dehumidification [11].

(3) AP compatibility with Asari Radix et Rhizoma, which has the functions of dispelling wind and dehumidification, dredging paralysis, and relieving pain [11].

(4) AP compatibility with Taxilli Herba, which has the functions of dispelling wind and dehumidification, tonifying kidney, and dredging paralysis [12].

(5) AP compatibility with Rehmanniae Radix, which has the functions of tonifying liver, kidney, and blood, strengthening tendons and bones, tonifying yin, and promoting fluid production [12].

(6) AP compatibility with Angelicae sinensis Radix, which has the functions of tonifying blood and dispelling wind [12].

(7) AP compatibility with Typhonii Rhizoma, which has the functions of dispelling wind, dehumidification, relaxing muscles and activating collaterals, and relieving pain [12].

(8) AP compatibility with Ligustici Rhizoma et Radix, which has the functions of dispelling wind and dehumidification, dissipating cold, and relieving pain [12].

(9) AP compatibility with Schizonepetae Herba, which has the functions of dehumidification and relieving spasm, relaxing muscles, and activating collaterals [12].

(10) AP compatibility with Ephedrae Herba, which has the functions of dispelling wind and removing fever, dehumidification, and relieving pain [12].

(11) AP compatibility with Notopterygh Rhizoma et Radix, which has the functions of dispelling wind and dehumidification, dredging paralysis, and relieving pain [13, 14].

(12) AP compatibility with Gentianae Macrophyllae Radix, which has the functions of dispelling wind and dehumidification, dredging paralysis, and relieving pain [15].

(13) AP compatibility with Phellodendri Amurensis Cortex, which has the functions of dehumidification and antipyretic [15].

The commonly used clinical prescriptions include Duhuo-Jisheng decoction [26], Duhuo-Cangzhu decoction, Duhuo decoction [27], Duhuo-Xixin decoction [28], and Duhuo pulvis [29]. Among them, Duhuo-Jisheng decoction is most widely used in clinical practice, which has good effects on rheumatoid arthritis, rheumatoid arthritis, knee osteoarthritis, lumbar disc herniation, headache, stroke, hemiplegia, and other diseases. The dosage forms involved include decoction, liquor, tablet, capsule, pill, aerosol, liniment, powder, paste, etc. [2] (as shown in Table 1).

In addition, it is also used in health care, beauty, and other fields. As early as in Sheng Nong's herbal classic, it is recorded that "taking AP for a long time has weight loss and antiaging effects." The AP wine is recorded in Qianjinfang, "Medicinal tea for all kinds of diseases" records the AP tea. Peaceful Holy Benevolent Prescriptions records the AP-Ginseng Radix et Rhizoma wine. General Records of Holy Universal Relief records the AP-Angelicae Sinensis Radix wine. In recent years, there are several patented inventions in health care and cosmetics. A kind of AP internal injuries fever health tea (CN. 2012103901941) [30], a kind of beauty dispelling wet medicinal wine (CN. 201710879392) [31], a beauty mask cream (201710782640.6), etc. [32].

4. Chemical Component

4.1. Coumarins. Coumarin compounds is the general name of o-hydroxycinnamic acid lactones with the basic skeleton of benzo [alpha]-pyranone, which are one of the main components of AP [33]. In addition, Chinese Pharmacopoeia (2015 edition) also uses two coumarin components, osthol and columbianadin, as the quality control indexes of AP.

At present, more than 120 kinds of coumarins have been isolated from various varieties of AP, including furanocoumarins [34], pyranocoumarins [35], dicoumarins [35], simple coumarins [36-41], and individual coumarin glycosides [42]. The components of coumarins isolated from AP are listed in Table 2, and the structures are shown in Figure 1.

4.2. Volatile Oils. Volatile oil is a group name of volatile oil-like compounds which has aromatic smell and can be distilled with water vapor without being miscible with water [46]. The volatile oil is a kind of mixture with relatively complex compounds. There are a large number of volatile oil components in AP, mainly including terpenoids, aromatic compounds, and aliphatic compounds [44,47-60], which is shown in Table 3. Gao et al. analyzed the volatile oil compounds from the water extract of AP and Heracleum candicans Wall ex Dc dried roots by GC/MS and identified 32 and 45 compounds, respectively [62]. Zhang et al. extracted the volatile oil compounds from the water extract of Heracleum hemsleyanum Diels dried roots and identified 53 compounds [63]. Wang et al. extracted and compared the volatile oil compounds of the dried roots and rhizomes of AP and Angelica dahurica (Fisch) Benth et Hook, and 90 compounds were detected and 52 were identified from AP; 57 compounds were detected from the dried roots and rhizomes of Angelica dahurica (Fisch) Benth et Hook and 37 were identified [64]. Yang et al. used steam distillation to extract the volatile oil from AP and detected 229 chromatography peaks by GC-MS and identified 88 compounds [65]. Zhang et al. extracted the volatile oil from the dried roots of Heracleum lanatum Michx by different extraction methods and identified a total of 59 compounds [61]. It has been reported that 40% of the small molecular compounds will change in the process of extraction and detection. Therefore, in this section, only list of the separated compounds from volatile oil of AP is discussed [66]. And, the compounds isolated and identified by these research studies are different, and even the same compounds have different content proportions in different varieties of AP, which may be related to the different species, climatic and environment of the cultivation area, soil conditions, processing methods of the production area, extraction facilities, and extraction conditions.

4.3. Organic Acids. Organic acid refers to a kind of acid organic compounds containing the carboxyl group, which has a variety of pharmacological effects such as antibacterial, antiviral, antidepression, antidiabetes, antitumor [66], antiinflammatory [67], antitussive, expectorant [68], and antioxidant [69]. With the first separation of 3-O-trans-coumaroylquinic acid, 3-O-trans-feruloylquinic acid, and other compounds from the methanol extract of the dried roots of AP by Yang et al., some scholars had developed great interest in organic acids compounds in AP [70]. Up to now, the organic acid compounds isolated from AP are far more than these (as shown in Table 4 and Figure 2). We believe that with the progress of time and the development of science and technology, the organic acids in AP will be studied more thoroughly.

4.4. Polysaccharides. Polysaccharide compounds have many pharmacological effects, such as antitumor [72], immunomodulatory [73], hypoglycemic [74], hypolipidemic [75], antioxidant [76], and antiaging [77]. Studies have shown that polysaccharides can be obtained from the above-ground parts of AP: 6-O-[beta]-D-apiofuranosyl-(1 [right arrow] 6)-[beta]-D-glucopyranosyl scopoletin, 7-O-[beta]-D-apiofuranosyl-(1 [right arrow] 6)[beta]-D-glucopyranosyl umbelliferone, 7-O-[beta]-D-glucopyranosyl umbelliferone, 3-O-[[beta]-D-galactopyranose-(1 [right arrow] 2) [[beta]-D-xylopyranose-(1 [right arrow] 4)]-[beta]-D-pyranoglucuronic acid] -28-O-[beta]-D-pyranogluconoleanolic acid, 3-O-[[beta]-D-galactopyranose-(1 [right arrow] 2)-[beta]-D-pyranoglucuronic acid]-O[[beta]-D-galactopyranose-(1 [right arrow] 2)-[beta]-D-pyranoglucuronic acid]-28-O-[beta]-D-pyran glucose ivy saponins, 3-O-[[beta]-Dgalactopyranose-(1 [right arrow] 2)-[beta]-D-pyranoglucuronic acid]-28O-[beta]-D-pyranogluconoleanolic acid, 3-O-[[beta]-D-galactopyranose-(1 [right arrow] 2)-[beta]-D-pyranoglucuronic acid] oleanolic acid, 3-O-[[beta]-D-xylopyranose-(1 [right arrow] 4)-[beta]-D-pyranoglucuronic acid]-28-O-[beta]-D-pyran galactose oleanolic acid, 3-O-[[beta]-Dxylopyranose-(1 [right arrow] 4)-[beta]-D-pyranoglucuronic acid]-28-O[beta]-D-pyranogluconoleanolic acid, 3-O-[[beta]-D-xylopyranose(1 [right arrow] 4)-[beta]-D-pyranoglucuronic acid]-hederagenin, 3-O[[beta]-D-xylopyranose-(1 [right arrow] 4)-[beta]-D-pyranoglucuronic acid]oleanolic acid, 3-O-[beta]-D-pyranoglucuronic acid-28-O-[beta]-Dpyranogluconoleanolic acid, and 3-O-[beta]-D-pyranoglucuronic acid-oleanolic acid [9,42,48].

4.5. Others. There are also compounds like adenine riboside, adenosine, allantion, angesesquid A, angesesquid B, 2,3,4,9 -cartrahyd-ro-l-H-pyridio[3,4,-b]indole-3-carboxylic acid 1, [alpha]-caryophyllene, coclaurine, daucosterol, glyceride, glucose, liriodenine, 1-N-methylcoclaurine, oleanic acid, sucrose, [beta]-sitosterol, uridine, diterpenic acid, diterpene alcohols, and other compounds and Al, As, B, Ba, Ca, Cd, Co, Cr, Cs, Cu, Fe, Ge, Hg, K, Mg, Mo, Mn, Na, Ni, P, Pb, Se, Sr, Zn, and other trace elements in AP [78].

In this section, the chemical constituents of AP are summarized, which is helpful to further study on the material basis of its efficacy and explore the principle of its prevention and treatment of diseases. And, it also can provide an effective scientific basis for the development of new drugs, the expansion of drug sources, the synthesis of lead compounds or new drugs, the adaptation to clinical use, and the expansion of its market application.

5. Analysis Method and Quality Control

There are many kinds of compounds in AP, and their analysis methods are various. And, volatile oil compounds are often detected by gas chromatography-tandem mass spectrometry (GC-MS) [56]. The authors in [79] used the colorimetry method to determine the content of total coumarins in AP. However, the sample preparation of this method is complex and time consuming. Subsequently, thin layer chromatography (TLC) was used to determine the content of columbianetin. Although this method is simple, it is not precise enough and is not ideal for the separation of multicomponent compounds [64]. Some scholars used high-performance liquid chromatography (HPLC) [80-83], high-performance liquid chromatography in tandem with diode array detector (HPLC-DAD) [84,85], high-performance liquid chromatography in tandem with ultraviolet detector (HPLC-UV) [86,87], ultraperformance liquid chromatography-photo diode array detection(UPLC-PDA) [88], and other methods to determine the flavonoids, coumarins, and other compounds with UV absorption in AP. The above methods can analyze the compounds in AP and have good separation effect and stability. However, these methods are not suitable for compounds with no UV absorption or only terminal absorption. There are also scholars who used ultrahigh-performance liquid phase tandem mass spectrometry (UPLC-MS/MS) to determine more than 40 chemical components such as coumarins and phenolic acids in AP. Hou et al. used ultrahigh-performance liquid phase tandem single quadrupole mass spectrometry (UPLC-QDA) to establish the fingerprint of AP, which not only analyzed the type and quantity of the whole compound of AP, but also made up for the deficiency that the above method could not detect compounds with no UV absorption. Wang et al. used high-performance liquid chromatography in tandem with fluorescence detection (HPLC-FD) to determine umbelliferones and scopoletins in AP. The results show that this method is easy to operate, economical, and practical [72]. Yang et al. used ultraperformance convergence chromatography (UPCC) and C[O.sub.2] as the mobile phase to establish the fingerprint of AP, which has the advantages of environmental friendliness, green, and so on [89]. It makes up for the shortcomings of common organic reagents used in the past to pollute the environment [33]. And, other methods are also often used in the detection of coumarin compounds. Among them, HPLC is the one of the most frequently used analysis methods, and it is also the main method for the analysis of other compounds in AP.

In addition, most of these methods have the advantages of rapidness, precision, accuracy, high sensitivity, short analysis time, strong separation ability, good selectivity, simple operation, low detection line, and wide application range. However, most of the methods have the disadvantages of complex sample pretreatment, high-end instruments and equipment, expensive price, use of toxic organic solvents, pollution of environmental soil, not green and environmentally friendly enough, and so on. But, we believe that with the development of science and technology, more and more low-cost and efficient instruments and green reagents will be developed.

The species of AP are complex and difficult to distinguish, which are easily affected by the growing environment, harvesting time, processing methods, and storage conditions. Moreover, the content of active components in AP is different in different areas. Due to these factors, the quality and clinical efficacy of AP cannot be controlled at present.

Currently, the 2015 edition of Chinese Pharmacopoeia uses TLC for the qualitative identification of AP and HPLC for the determination of the content of osthol and columbianadin. Moreover, it is stipulated that AP should contain osthol no less than 0.50% and contain columbianadin no less than 0.080%.

However, TCM has the characteristics of multicomponent and multitarget. It is limited to evaluate the quality of TCM only by the content of one or two compounds. In order to evaluate the quality of AP, Yang et al. used the UPLCPDA method to determine the content of 6 phenolic acids and 7 coumarin compounds [90]. Ding et al. determined the content of coumarin by LC-MS/MS [91]. Yang et al. used the UPLC-MS/MS method to determine the content of 15 compounds in AP and found that columbianetin acetate, osthol, chlorogenic acid, and psoralen were the main components causing the differences in AP from different sources. Hou et al. established the UPLC fingerprint of AP, which again proved that columbianetin acetate and osthol were the main components that caused the difference of AP in different areas [92]. However, there are few methods to evaluate the quality of AP in relation to its pharmacological activity. It is obviously not enough to evaluate AP quality solely on the basis of chemical components. More methods should be established by quality evaluation related to activity or based on chemical activity.

6. Processing Method

Processing can remove nonmedicinal parts, keep the active ingredients, make the drug pure, reduce toxicity, detoxify, and change the drug ingredients to enhance the efficacy. Thunder gong processing theory ([phrase omitted]) recorded that there was a steaming method of epimedium in the Northern and Southern dynasties. Lishang Xuduan Fang ([phrase omitted]) recorded that there was the method of removing reed in the Tang dynasty. The Song dynasty had to collect the reed and then wash and bake them. Decoction and Material Medica ([phrase omitted]) recorded there was a method of peeling and then washing in the Yuan dynasty. In the Ming dynasty, salt water immersion baking was practiced (Prescriptions for Universal Relief ([phrase omitted])), and also removing section to fry (Surgical Cases ([phrase omitted])) and wine wash method (Curative Measures for All Diseases ([phrase omitted])) The Qing dynasty has the wine stir-fry (Chuanyabu ([phrase omitted])), the wine immersion method (Gynecology jade ruler ([phrase omitted])), and so on. Currently, there are net preparation, cut preparation (2015 edition Chinese Pharmacopoeia), and frying method (Integration of Medicine ([phrase omitted])).

7. Pharmacological Effects

As a traditional Chinese medicine, AP has a variety of effects, such as anti-inflammatory [93], anti-rheumatism, sedation [94], hypnosis, neuroprotection [95], antioxidation [96], antitumor [97], and antigastric ulcer [98], which has been studied and confirmed by many scholars. At present, the pharmacological effects of AP are summarized in Table 5, which is described in detail as follows.

7.1. Analgesic, Sedative, and Anti-Inflammatory Effect. The decoction of AP has sedative and hypnotic effects on rats and mice and can prevent the convulsive effect of strychnine on frogs but it cannot prevent them from dying. Li et al. studied the anti-inflammatory effect of the AP ethanol extract of different concentrations on cotton ball implantation and found that 60% and 80% ethanol extract had antiinflammatory effect (P < 0.05), while 40% ethanol extract had no such effect [93]. The fingerprint-effect relationship of AP was established by Hou et al., whose research results showed that the extract of AP had significant inhibitory effects on the pain and inflammatory reactions of mice caused by hot plate (P< 0.01), acetic acid writhing (P < 0.01, the analgesia rate could reach 89.27%), formalin (P < 0.01, the analgesia rate could reach 52.91%), ear swelling (P < 0.01, the inhibition rate of swelling was up to 69.33%), caused by xylene, and foot swelling (P < 0.01, the inhibition rate of inflammation was 23.49%), caused by carrageenan. Even the analgesic and antiinflammatory activity of AP from some places was stronger than that of the positive drug aspirin. The analysis of fingerprint-effect relationship has shown that osthol, bergapten, columbianetin acetate, and isoimperatorin were the main active components with anti-inflammatory and analgesic effect of AP [92]. However, this study used only a single dose and lacked a dose-dependent study.

Fan et al. studied the analgesic and anti-inflammatory effects of the volatile oil components of AP. The anti-inflammatory effects were observed by the swelling of rats' feet caused by egg white, and the analgesic effects were observed by the hot plate method and acetic acid writhing method in mice. The result showed that the components of volatile oil had no obvious analgesic effect on the pain of mice caused by hot plate, the high dose of the AP volatile oil group could significantly reduce the number of writhing of mice caused by acetic acid (P < 0.05, the analgesia rate could reach 76.8%), and the low and high dose of AP volatile oil groups both had a good anti-inflammatory effect on the foot swelling of rats caused by egg white (P < 0.01). However, this study only speculated that the anti-inflammatory and analgesic effects of volatile oil in AP were related to the release of 5-HT, and the relevant mechanism was not studied [94].

The study by Qiu et al. found that the ethanol extract of AP had different degrees of inhibition on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). With the increase in the dosage of AP, the inhibitory effect was enhanced, which may also be one of the anti-inflammatory mechanisms of AP [99]. And other studies had shown that AP has analgesic effects by acting on the central and peripheral nervous systems [117]. And, the coumarin compounds in AP could inhibit the increase in peritoneal and skin vascular permeability induced by histamine and bradykinin, suggesting that the anti-inflammatory effect of AP might be related to the inhibition of histamine and bradykinin. Ma established a neural injury model to study the analgesic effect of coumarins in AP, finding that AP has the analgesic effect mainly related to reducing the concentration of proinflammatory cytokines of TNF-[alpha], IL-1[beta], and IL-6 in the neural injury model and reduces the expression of TRPV1 and perk in the damaged neurons, which also indicated that it may be related to the presence of osthol and columbianadin in AP [102].

Sun et al. studied the hydrolytic activity of N-acylethanolamine-hydrolyzing acid amidase (NAAA) and its anti-inflammatory effect on the LPS-induced mouse macrophage RAW 264.7 inflammatory response model. The results showed that the volatile oil of AP could inhibit the hydrolysis activity of NAAA and increase the level of N-palmitoylethanolamine (PEA) in RAW 264.7 cells induced by LPS, thereby downregulating the expression of TNF-[alpha], iNOS, and IL-6 mRNA and inhibiting the release of TNF-[alpha] and NO in RAW 264.7 cells to play an antiinflammatory effect [100]. Li et al. found that angesesquid A and angesesquid B could inhibit the release of nitric oxide (NO) in the inflammatory model cells of chondrocytes of intervertebral disc in vitro (P < 0.001), thus inhibiting the occurrence of inflammatory response. However, both methods lacked a positive control group [101].

7.2. Cardiovascular Effect. The alcohol extract of AP could inhibit the platelet aggregation induced by ADP in rats and the thrombus formed by the Chandler method and could also shorten the length of the thrombus and prolong the time of tail hemorrhage in mice. Moreover, the inhibition rate of platelet aggregation was enhanced with the increase in the AP alcohol extract concentration. When the AP alcohol extract concentration reached 0.4 g/kg, it had an inhibitory effect on the thrombosis formed by carotid vein bypass in rats (P < 0.05), and when the AP alcohol extract concentration reached 1.0 g/kg, the inhibition rate could reach 51.1% (P < 0.01). However, the method lacked a positive control group and failed to provide reliable data for clinical application. At the same time, only the AP alcohol extract was studied in this study, and there was no research on related bioactive monomer compounds [103].

Some studies had proved that the active ingredients of antiplatelet aggregation and antithrombotic activity were columbianetin acetate, columbianetin, osthol, and columbianedin [118]. Li et al. research showed that gamma-aminobutyric acid (GABA) was one of the main active components of AP, which had antiarrhythmic effect. Gamma-aminobutyric acid (10 mg/kg, iv) could prolong the start time of ventricular arrhythmia induced by aconitine in mice (control group 1.7 [+ or -] 0.12 min and GABA group 2.0 [+ or -] 0.4 min, P < 0.05) and increased the threshold dose (control group 80.9 [+ or -] 9.4 g/kg and GABA group 94.3 [+ or -] 15.0 g/kg, P < 0.05). Gamma-aminobutyric acid (10 mg/kg, iv) could delay the start time of arrhythmias induced by aconitine in rats (control group 3.5 [+ or -] 1.1 min, GABA group 13.2 [+ or -] 8.8 min, P< 0.05), reduce the incidence of ventricular tachycardia (control group 100%, GABA group 50%, P < 0.05), shorten the duration of ventricular tachycardia (control group 22.2 [+ or -] 6.9 min, GABA group 12.3 [+ or -] 0.5 min, P < 0.05), and reduce the mortality of ventricular fibrillation (control group 50%, P < 0.05). Gamma-aminobutyric acid (10mg/kg, iv) also had an effect on ventricular action potential in rats, which could reduce APA and APO 50 and APO 90. However, this experiment lacked a positive control group and a comparison between the pharmacodynamics of gamma-aminobutyric acid and the AP crude extract [104].

Chen et al. used Compound Danshen as the positive control group to study the function of activate blood and resolve stasis of the AP alcohol extract. It was found that it can also significantly reduce the whole blood viscosity, plasma viscosity, and red blood cell aggregation index of vertigo patients and increase the velocity of blood flow in cerebral vessels. The results showed that AP alcohol extract treatment was effective, with an effective rate of 95.5%, which was significantly higher than the control group (P < 0.05, the effective rate was 79.5%). This showed that the AP alcohol extract could play a good role in activating blood and resolving stasis. However, this study only used a single dose for clinical research, lacking dose-dependent studies and studies on the maximum safe dose of AP [105]. We speculate that the possible mechanism of AP is related to dilation of blood vessels, reduction of blood viscosity, and improvement of microcirculation. It may also be related to

GABA contained in AP, increase in cardiac pump function, and influence of the cardiac output. The future scholars should also discuss the specific pharmacodynamic substances that can activate blood circulation and remove blood stasis in the ethanol extract and analyze and verify the pharmacodynamic substances and possible metabolites through in vivo and in vitro pharmacological experiments, which will be of certain reference value for future studies.

Some studies had also shown that the AP root water extract at low concentration could effectively inhibit the proliferation of human microvascular endothelial cells [97] Chen and Lu showed that AP had a good diastolic effect on vasoconstriction caused by PE and KCl, and its mechanism was related to the influx of Ca[Cl.sub.2] [106]. Hu et al. discussed the inhibitory effect and mechanism of AP on angiogenesis and considered osthol as the main component of antiangiogenesis in vitro. The inhibition rates of treating with 3.75-30 [micro]g/ml AP extract and osthol for 48 h on cell proliferation of HUVEC were 5.16%-10.15% and 22.64%-65.56% and those of LoVo cells were 2.86%-7.29% and 5.15%-24.39%, respectively. The inhibition rates of treating with 3.75-30 [micro]g/ml AP extract and osthol for 24 h on HUVEC cell migration were between 2.16%-8.00% and 13.70%-63.04%, and the apoptosis rates of HUVEC cells were between 6.1%-14.4% and 18.8%-89.5%, respectively. The results showed that the effect of osthol on the cell cycle was stronger than that of the AP alcohol extract [119], which laid a foundation for AP to become a clinical Chinese medicine for antiangiogenesis.

7.3. Neuroprotective Effect. The ethanol extract of AP could improve the learning and memory ability of aging mice by improving the aging of phospholipid components in different parts of the cerebral cortex, hippocampus, and striatum, increasing the concentration of phosphatidylcholine (PC), reducing the content of sphingomyelins (SM), and improving the aging changes of the thymus and hippocampus [94]. It also shown that the mechanism of AP delaying brain aging was related to its antiperoxidation damage of free radicals, reducing the immunosuppression of arachidonic acid metabolites and antagonizing brain inflammation [94]. A study showed that brain aging was related to the increase in malondialdehyde (MDA) content and DNA fragment deletion in brain tissues, and the AP decoction and alcohol extract could reduce the content of MDA and the deletion of the DNA fragment in natural aging mice [96]. Moreover, the effect of the alcohol extract was better than that of the water extract, which may be related to the more effective component coumarin in the alcohol extract [120]. Pei et al. found that the mechanism of the neuroprotective effect of coumarin in AP was related to the inhibition of the content of excitatory amino acid Glu in brain tissues and serum and the inhibition of the expression of the stress factors CHOP and Caspase12 in the substantia nigra in brain tissues [107,108,121]. Li et al. found that AP could significantly improve the activity of mitochondrial respiratory chain enzyme complex I and IV in the brain of aged mice and had a protective effect on the oxidative damage of mitochondrial DNA in mice [109]. Zhang et al. showed that AP could inhibit the expression of IL-1, IL-6, TNF-[alpha], p38MAPK, and iNOS in rat brain tissue by regulating NF-[kappa]B and increase the ratio of Bcl-2/Bax to reduce the occurrence of inflammation, apoptosis, oxidative stress, and other reactions in brain tissue. AP could also play a neuroprotective role by inhibiting the ability of spleen lymphocytes to secrete proinflammatory factors and increasing the expression of the neurofilament protein [110]. Yu found that the AP root ethanol extract could delay the occurrence of Alzheimer's disease by increasing serum superoxide dismutase (SOD) and reducing acetylcholine esterase (AChE) in brain tissue [111]. Osthol in AP could regulate Jak-SAKT, MAPK, PI3K, TGF-[beta], phosphatidylinositol, and other signaling pathways by participating in the metabolism of glycerol phospholipid, purine, niacin, and nicotinamide. Activation of the PI3K/Akt signaling pathway increases the survival rate of BM-NSCs and inhibits apoptosis to protect BM-NSCs injured by H2[O.sub.2] [112]. We speculated that after being absorbed into the body, osthol would undergo a series of metabolic reactions to form a lipid soluble metabolite, which would pass through the blood-brain barrier and play a neuroprotective role. But, the metabolomics of osthol at the animal and cellular levels has not been studied. In the future research, the mechanism of action and metabolomics of monomer compounds which play an important role should be studied and analyzed.

By regulating the Notch signaling pathway, BM-NSCs can be promoted to express and differentiate into cholinergic neurons, which can play a role in Alzheimer's disease [114]. And, it played a neuroprotective role by promoting the expression of cyclic adenosine phosphate reactive element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) and increasing the expression of p-CREB and BDNF [114]. However, most of the above studies focused on the crude extract of AP, and there were few studies on the monomer compounds in AP. In the future, monomer compounds should be studied and analyzed, and their unknown mechanism of action in clinical treatment should be clarified.

7.4. Antibacterial Effect. It had been reported that AP decoction had significant inhibitory activity on tubercle bacillus and brucella [117]. And, the chloroform extract of Angelica polyclada Franch showed inhibition effect on Bacillus subtilis and Escherichia coli, among which the inhibitory activity against Escherichia coli was stronger than that of Bacillus subtilis [34]. Zhang et al. used the growth rate method to test the inhibitory effect of the extracts from the petroleum ether layer of AP on the growth of 12 kinds of pathogenic bacteria mycelium. The experimental results showed that the extract had antibacterial effect on the tested bacteria, the experimental results showed that AP had different antibacterial effects on 12 tested fungi, and the inhibition rate of Rhizoctonia solani was the strongest, reaching 100%, followed by Sclerotinia sclerotiorum and Phytophthora capsici, reaching over 80%, while for Exserohilum turcicum and Magnaporthe oryzae, the inhibition rate was relatively low, and preliminarily identified pimpinellin was the main active component, with strong antibacterial activity [115]. Li et al. isolated and studied the antibacterial active components of the ethanol extract of AP and the results showed that isobergamolactone, sphondin, pimpinellin, and isopimpinellin were the main antibacterial substances, and the EC50 of isobergamolactone, pimpinellin, and isopimpinellin on citrus anthrax was 45mg/L, among which sphondin had the best inhibitory activity on citrus anthrax, and its EC50 was 41.5216 mg/L [116]. However, the absence of the positive control group and the blank control group and a lack of dose-dependent effects were two limitations of the studies.

7.5. Antioxidation Effects. Min et al. found that the antioxidant effect of AP was related to the polyphenol compounds contained in it. The study by Chen et al. had shown that the content of malondialdehyde (MDA) in the brain tissues of mice could be reduced by the decoction and alcohol extract of AP, and the effect of the AP alcohol extract was better than that of the water extract, which may be related to the more effective compound coumarin contained in the alcohol extract [96].. Studies by Hou et al. showed that the alcohol extract of AP could inhibit the concentration of MDA in the mouse plasma, and the inhibitory rate could reach 23.49%. Zhang and Du found that AP could delay the occurrence of Alzheimer's disease by increasing the level of serum superoxide dismutase (SOD) [111]. And, Lu and Zhang showed that the ethanol extract of AP had significant antioxidant effect on five edible oils. However, the study was carried out at a single dose and lacked concentration dependence [122]. As a common TCM, AP has high safety and is widely distributed in various provinces of China. If further study is performed on its antioxidant activity, it is considered possible to make it a natural antioxidant.

7.6. Antitumor Effect. Zou et al. studied different concentrations of AP extracts at the cellular level and found that AP inhibited proliferation of human liver cancer cell lines (SMMC-7721) and human umbilical vein endothelial cells (HMVECs) in a dose-dependent manner, with an IC50 value of 1.59 mg/ml. Under the inhibition of 20% of SMMC-7721, the inhibition of HMVECs was more than 50%, showing that there was a significant dose difference between the two cell lines [96]. Lin et al. showed that psoralen, bergapten, xanthotoxin, umbelliferone, osthol, isoimperatorin, and other compounds in AP had antitumor effects, and their antitumor mechanisms may be related to inducing tumor cell apoptosis, inhibiting tumor cell DNA replication, inhibiting tumor cell multidrug resistance, and inhibiting tumor cell metastasis [4,123]. However, this was only the study on the antitumor mechanism of monomer compounds, not AP. And, few studies had conducted comparative studies of the antitumor effects of the crude AP extract and specific compounds in AP. In the future, scholars should also screen out the compounds whose antitumor effects of AP play a dominant role and strengthen their studies on cell and animal levels.

7.7. Others. The study by Dan et al. showed that chloroform, petroleum ether, and ethyl acetate extracts of AP had significant antigastric ulcer effects [98]. Psoralen-derived compounds, such as bergapten, xanthotoxin, and other compounds, could cause solar dermatitis in humans. Although some experiments had shown that AP has antigastric ulcer and sensitization effects, its mechanism had not been elucidated.

8. Toxicity

Bielu records "AP as sweet, lukewarm, and nontoxic." The 2015 edition of the Chinese Pharmacopoeia stipulates that the safe dose of AP is 3-10 g per day for adults. Studies have shown that AP contains xanthotoxin, bergapten, psoralen, and osthol, all of which have a certain degree of photosensitivity. Taking too much AP may cause a range of toxic effects. It was recorded in the Chinese Materia Medica ([phrase omitted]) that the LD50 of intramuscular injection of xanthotoxin in rats was 160 mg/kg and the LD50 of bergapten was 945mg/kg. 400mg/kg xanthotoxin could cause death and adrenal hemorrhage in guinea pigs. 200-300 mg/kg xanthotoxin could cause liver turbidity, fatty change, acute hemorrhagic necrosis, severe renal congestion, and hematuria. Continuous administration of 1-2 mg/kg xanthotoxin for 5 months could lead to liver necrosis. The LD50 of osthol intraperitoneally injected in mice was 16mg/kg [25].

Another report was on two cases of AP poisoning: (1) a male, 9 years old, accidentally ate AP about 100 g, and 1h after eating, he began to vomit, was irritable and incoherent, had whole bodies convulsions, went into coma, and finally died; (2) a male, 7 years old, accidentally ate AP about 50 g, and 1 h after eating, he began to vomit and had restlessness. Physical examination revealed the following: body temperature was 36.2 [degrees]C, pulse was 82 times/min, blood pressure was 100/80, dilated double pupils, slow response to light, arrhythmia, peripheral blood leukocytes were 20400, neutrophils were 83%, and lymphocytes were 17% [124].

Kunming mice were used for the acute toxicity test, and the results showed that 10 minutes after oral administration of large dose (15.80 g/kg), the mice developed symptoms of poisoning such as tail tip cyanosis, restlessness, and accelerated breathing, and some of the mice died due to respiratory failure, LD50 was 7.35 [+ or -] 0.62 g/kg. Long-term toxicity tests were conducted on Wistar rats and hybrid dogs. The results showed that 10 min after oral administration of large dose (825 mg/kg), the rats developed symptoms of poisoning such as tail tip cyanosis, restlessness, and rapid breathing. However, the poisoning symptoms disappeared 30 days after oral administration. The growth rate of the high-dose group was slower than that of the control group (P < 0.01). Pathological examination revealed gastric flatulence and mucosal edema in some rats. Under a light microscope, hyaline bodies were observed in a few rats and dogs (138mg/kg) in the high-dose group [125].

At present, there are few studies on the toxicity of AP, and future scholars should focus on the toxicity of AP. In order to ensure the safety and efficacy of AP, toxicity evaluation can provide guidance for clinical drug efficacy and patient safety [126].

9. Conclusion and Prospect

AP, as a famous TCM, with complex chemical components and extensive pharmacological effects, has been widely used in China for more than 2000 years. Scholars have done a lot of research on AP. So far, more than 120 coumarin compounds and 220 volatile oils compounds had been isolated from AP. It has also developed from the initial treatment of rheumatism alone to the modern prevention and treatment of tumor, cardiovascular and cerebrovascular diseases, and various arthritis diseases, which provides great help for its development and clinical application. However, there is still a lot of work to be done on the development and utilization of AP.

First, for the quality control of AP, the species of AP are complex, and the species of AP collected in different regions are not the same, and the identification of appearance and character alone is not perfect. Therefore, further research and demonstration are needed to identify authentic AP products, substitutes, and differences in their efficacy. The Chinese Pharmacopoeia takes the dry root of Angelica pubescens Maxim, f. biserrata Shan et Yuan as authentic AP product, which only takes the content of osthol and columbianadin as the quality control standard of AP, which lacks reliability because there is no research to prove that these two compounds are bioactive substances of AP. And, we should analyze the whole characteristics of AP to find out the most effective active ingredients and establish the quality control standard of AP on this basis.

Second, the processing of TCM has the effect of enhancing effect and reducing poison, which is widely used in the processing of TCM. However, there are no reports on processing AP in modern studies including phytochemistry, pharmacology, pharmacodynamics, and pharmaceutical analysis. Studies have shown that APR enters the kidney meridian and bladder meridian. It has a better pharmacological effect among TCMs which enters the kidney meridian after being baked with salt or wine. We speculate that AP can induce the decline of the body after salt roasting, which can better treat knee osteoarthritis and increase the analgesic function of the drug. And, AP after wine roasting can induce medicine to go to the top of the body, relieve headache better, and enhance the effect of blood circulation and activating collaterals. Therefore, it is necessary to study the processing products of AP, which can also fill the gap of AP processing.

Third, the research on the pharmacodynamic substances of AP is not thorough, and the mechanism, target, and pathway of the action of the active ingredients on the disease have not been scientifically clarified. Modern scholars can consider using network pharmacology, data mining, and virtual screening techniques to predict the chemical components and pharmacological activity related to the target, receptor, and pathway and verify through pharmacological experiments. In addition, new data mining methods can be proposed to screen herbs with similar effects, so as to reduce the development cost of new drugs by using natural drugs more effectively. And, most of the research studies focus on preliminary experiments in animals, and more in vitro studies at the cell level and more comprehensive clinical application are needed to further confirm its pharmacological mechanism. It is believed that with the innovation of the theories of phytochemistry, pharmacology, pharmacodynamics, etc., and the technical means of chromatographymass spectrometry, metabonomics, etc., a more scientific and reasonable quality control standard will be formulated, and the mechanism, target, and channel of its effective components will also be clarified, which will make up for the shortage of modern application of TCMs.

Fourth, in order to ensure safety and effectiveness, toxicity assessment can provide guidance for clinical efficacy and patient safety. At the same time, toxicity evaluation is also a prerequisite for the development of new drugs. However, there are few reports on the toxicity evaluation and the absorption, distribution, metabolism, and excretion of the main active components of AP in vivo. Future scholars should also study the toxicity and pharmacokinetic characteristics of the compounds in AP, so as to provide experimental basis for AP to become a new drug.

AP, as a TCM, plays an important role in maintaining human health. We hope that this paper can provide more understanding of AP and provide guidance for its future research. We also firmly believe that with the continuous deepening of the research on AP, its application can be extended from the clinical medicine field to health products, cosmetics, and other fields, and occupy a place in the world market.

[Please note: Some non-Latin characters were omitted from this article.]

https://doi.org/10.1155/2020/7460781

Data Availability

All reported or analyzed data in this review are extracted from published articles.

Conflicts of Interest

The authors declare no conflicts of interest.

Authors' Contributions

Haixue Kuang, Qiuhong Wang, Bingyou Yang, and Hai Jiang conceived and designed the review; Ajiao Hou, Wenjing Man, Xinyue Guo, Song Wang, and Jiaxu Zhang searched the literature and downloaded the documents and made classification; Ajiao Hou wrote the paper; and Liu Yang checked the chemical structures and formula and contributed comments for version of the manuscript. All authors read and approved the final manuscript.

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Grant nos. 81973604, 81803690, and 81703684), the Special Funds from the Central Finance to Support the Development of Local Universities, Postgraduate Funds for Heilongjiang University of Chinese Medicine (no. 2019yjscx013), the National Natural Science Foundation Matching Project (nos. 2018PT02 and 2017PT01), the Innovative Talents Funding of Heilongjiang University of Chinese Medicine (no. 2018RCD25), the Postdoctoral Initial Fund of Heilongjiang Province (UNPYSCT 2017219), the University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (no. UNPYSCT-2017215), the Natural Science Foundation of Heilongjiang Province (no. H2015037), the Heilongjiang University of Chinese Medicine Doctoral Innovation Foundation (nos. 2014bs05 and 2013bs04), the Application Technology Research and Development Projects of Harbin Technology Bureau (no. 2014RFQXJ149), and the Heilongjiang Postdoctoral Scientific Research Developmental Fund (nos. LBH-Q16210 and LBH-Q17161).

References

[1] S. Q. Chen, H. Q. Zhang, C. Q. Yuan, Y. Q. Deng, and G. Y. Chen, "Studies ON the coumarins from the Chinese crude drugs chuandh (root OF angelica pubescens maxim. F. Biserrata shan et yuan) and zhedh (root OF a. Pubescens maxim.)," Acta Pharmaceutica Sinica, vol. 17, no. 5, pp. 392-394, 1982.

[2] National Pharmacopoeia Committee, The Pharmacopoeia of the People's Republic of China, China Medical Science and Technology Press, China, 2015.

[3] L. Y. Zhang and M. X. Liang, "Exploration and analysis on the potential function of Radix Angelicae Pubescentis," Zhong Hua Zhongyao Zazhi, vol. 33, no. 1, pp. 46-49, 2018.

[4] L. Lin, X. P. Qian, and B. R. Liu, "Research progress on the chemical constituents and the anti-tumor activity of Angelica Pubescens," Journal of Modern Oncology, vol. 19, no. 2, pp. 373-376, 2011.

[5] X. L. Guo, X. M. Lin, J. Guo, and J. M. You, "The research status and prospect of radix angelicae pubescentis," Journal of Anhui Agricultural Sciences, vol. 42, no. 33, pp. 11673-11674, 2014.

[6] G. Zhou and B. H. Ma, "The development on the study of Radix Angelicae Pubescentis," China Modern Medicine, vol. 19, no. 16, pp. 15-16, 2012.

[7] Y. Zhu, F. Li, and Q. Y. Liu, "Research advances in the study of herbalism and pharmacology of traditional Chinese medicine of Radix Angelicae Pubescentis," Journal of Liaoning Economic Management Cadre Institute, vol. 1, pp. 68-69, 2010.

[8] W. Wang, Study on the Evaluation of Quality of Traditional Chinese Medicine Radix Angelicae Pubescentis, Liaoning University of Traditional Chinese Medicine, Shenyang, China, 2005.

[9] Y. T. Ma, "Studies on Radix Angelicae Pubescentis and Rhizoma Dioscoreae Nippomcae," Northwest University, Kirkland, USA, 2005.

[10] J. H. Liu, S. X. Xu, and X. S. Yao, "Research advances in the study of chemical constituents and pharmacology of Radix Angelicae Pubescentis," Journal of Shenyang College of Pharmacy, vol. 11, no. 2, pp. 143-150, 1994.

[11] C. Pan, "The compatibility, identification, application and application in veterinary clinic of Radix Angelicae Pubescentis," Journal of Veterinary Medicine, vol. 9, p. 235, 2014.

[12] G. B. Gong and H. L. Wu, "Clinical application of common drug pairs of radix angelicae pubescentis," Modern Journal of Integrated Traditional Chinese and Western Medicine, vol. 14, no. 20, pp. 2653-2654, 2005.

[13] H. Shen, L. C. Mu, F. Wang, and L. M. Xie, "Efficacy of a pair of notopterygii rhizoma et radix-angelicae pubescentis radix in external use," Chinese Journal of Experimental Traditional Medical Formulae, vol. 24, no. 15, pp. 228-234, 2018.

[14] K. X. Duan, Y. W. Li, H. B. Liu, and B. L. Wang, "Study on Anti-inflammatory mechanism of couplet medicine of notopterygium incisum-angelica pubescens based on network pharmacology," China Pharmacy, vol. 30, no. 9, pp. 1241-1246, 2019.

[15] W. Cao and C. C. Li, "Herb textual research on and common pairs of doubleteeth pubescent Angelica root," Journal of Shaanxi University of Chinese Medicine, vol. 41, no. 1, pp. 127-130, 2018.

[16] X. F. Cao and L. Zhou, "HPLC determination of osthole in DHjisheng pills," Chinese Practical Medicine, vol. 5, no. 9, pp. 36-37, 2010.

[17] J. Wang, J. Q. Chen, L. H. Yin et al., "HPLC simultaneous determination of glycyrrhizic acid and osthole in Extract of DH Gegen Decoction," Chinese Journal of Pharmaceutical Analysis, vol. 30, no. 3, pp. 2052-2054, 2010.

[18] L. L. Huang, "The clinical application of Radix Angelicae Pubescentis," China's Naturopathy, vol. 11, no. 8, pp. 45-46, 2003.

[19] Y. Xiang, S. H. Yang, G. X. Yao, S. J. Fan, and Z. W. Luo, "The cultivation techniques and medicinal value of Radix Angelicae Pubescentis," Special Economic Animal and Plant, vol. 7, pp. 27-28, 2019.

[20] L. Y. Du, J. C. Su, Q. Guo et al., "A AP cultivation method," 2020.

[21] G. X. Liu, "A AP cultivation greenhouse," 2019.

[22] J. Pan, "A method for cultivating high-quality AP," 2019.

[23] W. Wu, "A AP cultivation method for high qand high yield," 2020.

[24] Nanjing University of Chinese Medicine, ZhongYaoDaCiDian", Shanghai Science and Technology Press, Shanghai Science and Technology Press, China, 2nd edition.

[25] Editorial Board of National Administration of Traditional Chinese Medicine, The Chinese Materia Medica, Shanghai Science and Technology Press, China, 1999.

[26] P. Che, X. M. Ji, S. Liang, Y. Y. Zhang, and T. Han, "Anti-inflammatory and analgesic effects and change of serum 5HTP and 5-HIAA by DH jisheng decoction on adjuvant arthritis rats," Chinese Journal of Experimental Traditional Medical Formulae, vol. 20, no. 19, pp. 170-173, 2014.

[27] Y. L. Tang and J. K. Wang, "A preliminary study on the pharmacological effect of DH decoction," Journal of Traditional Chinese Medicine, vol. 24, no. 5, pp. 56-57, 2001.

[28] M. Hong, "The treatment of 120 cases of wind-dampness-cold joint pain with Duhui-Xixin decoction," Hubei Journal of Traditional Chinese Medicine, vol. 22, no. 4, p. 34, 1999.

[29] Q. J. Wang and Y. Wang, "Clinical efficacy of needle warming moxibustion combined with congrongduhuosan in treating ankylosing spondylitis with deficiency of kidney-yang type," Chinese Journal of Experimental Traditional Medical Formulae, vol. 16, 2020.

[30] B. M. Qian, "A kind of AP internal injuries fever health tea," 2012.

[31] D. N. Chen, "A kind of beauty dispelling wet medicinal wine," 2018.

[32] T. M. Yang, "A beauty mask cream," 2017.

[33] I. Pfeifer, A. Murauer, and M. Ganzera, "Determination of coumarins in the roots of Angelica dahurica by supercritical fluid chromatography," Journal of Pharmaceutical and Biomedical Analysis, vol. 129, pp. 246-251, 2016.

[34] Z. X. Wang, Y. Q. Shen, Y. J. Chen, and X. S. Yao, "Study on the active components of angelicae pubescentis maxim," Journal of Shenyang College of Pharmacy, vol. 5, no. 3, pp. 183-188, 1988.

[35] J. X. Pan, L. K. Arison, B. Smith, and J. G. Q. Han, "Separation and identification of iso-angelinol, anpubesol and other coumarins from Angelica pubescens Maxim, f. biserrata Shan et Yuan," Acta Pharmaceutica Sinica, vol. 22, no. 5, pp. 380-384, 1987.

[36] C. D. Wang, B. L. Qiao, S. Zhu, and L. H. Ju, "Chemical composition study of Angelica potymaropka Maxim," Northwest Journal of Pharmacy, vol. 6, no. 1, pp. 15-16, 1991.

[37] H. Q. Zhang, C. Q. Yuan, and G. Y. Chen, "Study on the chemical composition of Angelica biserraia," Chinese Traditional and Herbal Drugs, vol. 23, no. 10, pp. 515-516, 1992.

[38] G. F. Rao, Q. Yang, F. Cai, Q. M. Liu, and H. D. Sun, "The chemical composition of a Heracleum hemsleyanum Diels,"

Journal of Yunnan College of Traditional Chinese Medicine, vol. 17, no. 3, pp. 4-6, 1994.

[39] C. Y. Zhang, B. G. Zhang, and X. W. Yang, "Studies on the chemical constituents of the root of Angelica Pubescens F. Biserrata," Pharmaceutical Journal of Chinese People's Liberation Army, vol. 23, no. 4, pp. 241-245, 2008.

[40] Z. J. Cai, F. J. Dan, F. Cheng, J. Z. Wang, and K. Zou, "Chemical constituents of antibacterial activity fraction of Angelica polymorpha," Journal of Chinese Medicinal Materials, vol. 31, no. 8, pp. 1160-1162, 2008.

[41] X. F. Ding, X. Feng, Y. F. Dong, X. Z. Zhao, Y. Chen, and M. Wang, "Studies on chemical constituents of the roots of Angelica pubescens," Journal of Chinese Medicinal Materials, vol. 31, no. 4, pp. 516-518, 2008.

[42] X. F. Ding, X. Feng, Y. F. Dong, X. Z. Zhao, Y. Chen, and Y. Q. Liang, "Study on the coumarin components of Radix Angelicae Pubescentis," Chinese Traditional Patent Medicine, vol. 31, no. 7, pp. 1102-1104, 2009.

[43] Y. Zhu, "Comparison of the Active Components in Radix Angelicae Pubescentis of Different Places of Origin", Liaoning University of Traditional Chinese Medicin, Shenyang, China, 2007.

[44] X. W. Yang, Q. M. Guo, C. Y. Zhang, and B. G. Zhang, "Further studies on the chemical constituents of the root of Angelica pubescens f. Biserrata," PLA Journal of Pharmacy, vol. 24, no. 5, pp. 389-392, 2008.

[45] M. Wan, Y. Zhang, Y. Yang et al., "Analysis of the chemical composition of Angelicae Pubescentis Radix by ultra-performance liquid chromatogDHhy and quadrupole time-of-flight tandem mass spectrometry," Journal of Chinese Pharmaceutical Sciences, vol. 28, no. 3, pp. 145-159, 2019.

[46] J. P. Hou, "Research development on volatile oil from chuanxiong rhizome," Journal of Medicinal Plant Research, vol. 6, no. 12, 2012.

[47] S. Y. Jia and B. Wang, "Determination of volatile components of JiDuhuo(Angelica biserrata)by HS-GC-MS," Anhui Medical and Pharmaceutical Journal, vol. 18, no. 8, pp. 1429-1433, 2014.

[48] Z. Z. Wang, H. F. Tang, Z. W. Su et al., "Microscopical identification and chemical analysis of traditional Chinese medicine "Jiuyanduhuo"" Academic Journal of Second Military Medical University, vol. 18, no. 2, pp. 153-156, 1997.

[49] H. P. Yao and Y. B. He, "Analysis of the volatile components of DH (Angelica pubescens Maxim.f.biserrata) by gas chromatography-mass spectrometry and multivariate curve resolution," Guiding Journal of Traditional Chinese Medicine and Pharmacy, vol. 22, no. 15, pp. 54-57, 2016.

[50] X. X. Chen, C. Z. Han, and H. W. Yang, "GC-MS analysis of the essential oils from Angelica Pubescen s," Journal of Nanjing College of Pharmacy, vol. 17, no. 4, pp. 252-255, 1986.

[51] C. M. Zhou, C. Yao, and H. L. Sun, "Study on the chemical composition of volatile oil from Radix Angelicae Pubescentis," Journal of Chinese Medicinal Materials, vol. 13, no. 8, pp. 29-32, 1990.

[52] Y. Li, L. F. Wang, K. P. Liu, B. Yang, C. Du, and Y. Wang, "Investigation of transdermal effect and transdermal composition of volatile oil from notopterygium incisum, Angelica pubescens and pair of them by GC-MS," Chinese Journal of Experimental Traditional Medical Formulae, vol. 18, no. 18, pp. 46-51, 2012.

[53] Z. C. R. Dun, G. H. Zhu, Y. Cai, Y. K. Xiong, Z. H. Yan, and E. Yuan, "Determination of volatile components in Tibetan medicine Heracleum millefolium by HS-GC-MS," Chinese Traditional and Herbal Drugs, vol. 48, no. 11, pp. 2182-2188, 2017.

[54] L. X. Pu, T. J. Tang, X. H. Yuan, D. B. Hou, and B. Wang, "Study on essential oil constituents of aralia cordata thunb. from different habitats," Medicinal Plant, vol. 38, no. 17, pp. 8946-8948, 2010.

[55] Q. Q. Ai, B. X. Gao, Z. Q. Lan et al., "GC-MS analysis of volatile oil from Heracleum souliei radix," Journal of Chengdu University of Traditional Chinese Medicine, vol. 39, no. 1, pp. 15-17, 2016.

[56] X. Z. Xie, Y. L. Wang, X. J. Pan, and L. F. Huang, "Analysis of volatile oils components in radix angelecae pubescentis by GC-MS," Chinese Journal of Spectroscopy Laboratory, vol. 29, no. 1, pp. 317-319, 2012.

[57] H. Chen, C. H. Zhang, and H. Yang, "A comparative study on supercritical C[O.sub.2] extraction and microwave extraction of the volatile Oil in Heracleum hemsleyanum Diels," Lishizhen Medicine and Materia Medica Research, vol. 18, no. 11, pp. 2732-2734, 2007.

[58] X. P. Wang, J. X. Qiu, and S. Li, "Rapid GC-MS analysis of essential oils in radix angelicae biseratae," Journal of Yanbian University (Natural Science Edition), vol. 37, no. 2, pp. 128-131, 2011.

[59] Z. H. Hou and F. X. Zou, "Gas chromatogDHhy/mass spectrometry(GC-MS) analysis of the essential oil from Angelica pubescehs Maxim. by molecular distillation separation," Journal of Qilu University of Technology, vol. 29, no. 4, pp. 16-20, 2015.

[60] L. L. Huang, S. P. Xiong, Z. Zhou, M. X. Huang, and K. Q. Wang, "Comparative study on chemical components of the volatile oil from the root of Angelica pubescens in different habitats," Journal of Wuhan Botanical Research, vol. 20, no. 1, pp. 78-80, 2002.

[61] Z. X. Zhang and X. L. Yang, "Research on volatile oil obtained from heracleum moellendorffii with different methods," Journal of Shaanxi University of Science & Technology, vol. 27, no. 2, pp. 65-68, 2009.

[62] B. X. Gao, J. J. Deng, J. Zheng, and X. M. Lu, "GC-MS analysis of volatile oil from Radix Heracleum Candicans," Pharmacy & Clinics of Chinese Materia Medica, vol. 5, no. 5, pp. 9-10, 2014.

[63] C. Y. Zhang, B. G. Zhang, and X. W. Yang, "GC-MS analysis of essential oil from the radix of Heracleum hemsleyauum Diels," Research Information on Traditional Chinese Medicine, vol. 7, no. 12, pp. 9-12, 2005.

[64] X. T. Wang, X. Wang, Q. Cai, and Y. Q. Fu, "Comparisons of volatile oil and TLCS of radix angelicae pubescentis from sichuan and radix angelicae pubescentis from northeast," Liaoning Journal of Traditional Chinese Medicine, vol. 34, no. 5, pp. 638-639, 2007.

[65] X. W. Yang, Y. F. Liu, H. Y. Tao, Z. Yang, and S. Y. Xiao, "GC-MS analysis of essential oils from Radix Angelicae Pubescentis," Journal of Chinese Materia Medica, vol. 31, no. 8, pp. 663-666, 2006.

[66] M. Fang, J. Ivanisevic, H. P. Benton et al., "Thermal degradation of small molecules: a global metabolomic investigation," Analytical Chemistry, vol. 87, no. 21, pp. 10935-10941, 2015.

[67] D. L. Jones, "Organic acids in the rhizosphere: a critical review," Plant and Soil, vol. 205, no. 1, pp. 25-44, 1998.

[68] L. Yang, H. Jiang, A. Hou et al., "Simultaneous determination of thirteen Q-markers in raw and processed tussilago farfara L. By UPLC-QQQ-MS/MS coupled with chemometrics," Molecules, vol. 24, no. 3, 2019.

[69] L. Yang, H. Jiang, S. Wang et al., "Discovering the major antitussive, expectorant, and anti-inflammatory bioactive constituents in tussilago farfara L. Based on the spectrum-effect relationship combined with chemometrics," Molecules, vol. 25, no. 3, 2020.

[70] L. Yang, H. Jiang, X. Xing et al., "A biosensor-based quantitative analysis system of major active ingredients in Lonicera japonica thunb: using UPLC-QDa and chemometric analysis," Molecules, vol. 24, no. 9, 2019.

[71] E.A. Parfenov and L. D. Smirnov, "Pharmacological potential of antioxidants derived from coumarin (Review)," Pharmaceutical Chemistry Journal, vol. 22, no. 12, pp. 884-892, 1988.

[72] A.-H. Ge, W.-F. Ma, C.-P. Wang et al., "Ultra high performance liquid chromatography with photodiode array detector and quadrupole time-of-flight tandem mass spectrometry coupled with discriminant analysis to evaluate Angelicae pubescentis radix from different regions," Journal of Separation Science, vol. 37, no. 18, pp. 2523-2534, 2014.

[73] J. Wang and X. G. Gong, "Advances in studies on antitumor and immune regulation of polysaccharides," Chinese Journal of Biochemical Pharmaceutics, vol. 6, no. 4, pp. 674-682, 2001.

[74] Z. L. Xu, Q. Wamg, M. Zhao, Q. Xu, C. S. Jia, and Y. Y. Shi, "Test on the immunity-moderating function of Dioscorea oppostita thunb. Polysaccharide," Lishizhen Medicine and Materia Medica Research, vol. 18, no. 5, pp. 1040-1041, 2007.

[75] A. S. Luo, Z. Chun, S. R. Ge et al., "Effect of dendrobium denneanum polysaccharide reducing blood gllucose in vivo," Chinese Journal of Applied & Environmental Biology, vol. 12, no. 3, pp. 334-337, 2006.

[76] G. H. Zhou and G. P. Yu, "Effect study of auricularia polysaccharide on reducing blood lipid," Modern Food Science and Technology, vol. 21, no. 1, pp. 46-48, 2005.

[77] C. W. Sun and G. Z. Zhong, "Study on the antioxidant effects of Astragalus polysaccharide (APS)," Chinese Pharmacological Bulletin, vol. 12, no. 2, pp. 161-163, 1996.

[78] A. J. Hou, T. Y. Chen, S. P. Peng et al., "Study on anti-aging effect of poria cocos polysaccharide," Pharmacology and Clinics of Chinese Materia Medica, vol. 20, no. 3, pp. 10-11, 2004.

[79] Y. F. Yang, Y. B. Zhang, and X. W. Yang, "Simultaneous determination of 24 trace elements of Angelicae Pubescentis Radix by ICP-OES and ICP-MS methods based on the microwave digestion," Chinese Journal of Pharmaceutical Analysis, vol. 36, no. 11, pp. 2004-2008, 2016.

[80] X. Li and J. Yu, "Determination of total coumarin in Radix Angelicae Pubescentis," China Journal of Chinese Materia Medica, vol. 6, no. 9, pp. 543-545, 1991.

[81] Z. F. Sha, W. J. Sun, H. Gao, and M. L. Miao, "Determination of osthole and columbianetin acetate in Angelica pubescens by reversed phase HPLC," Acta Pharmaceutica Sinica, vol. 26, no. 10, pp. 798-800, 1991.

[82] Y. X. Chang, Z. W. Zhu, J. Li, Q. H. Zhang, and X. W. Qin, "Simultaneous determination of the seven major constituents for quality control of radix angelicae pubescentis by HPLC coupled with chemometrics methods," Journal of Inner Mongolia University, vol. 42, no. 2, pp. 215-223, 2011.

[83] Y. H. Shi, S. M. Zhao, R. Wang, H. S. Tan, G. X. Yu, and Z. T. Wang, "Simultaneous determination of osthole and columbianadin of Radix Angelicae Pubescentis by reversed phase high performance liquid chromatogDHhy," Chinese Pharmaceutical Journal, vol. 45, no. 16, pp. 1270-1273, 2010.

[84] Y. L. Li and M. H. Gao, "Columbianctim in Angelica Pubescens maxim. F.biserrata shan et yuan by RP-HPLC," Guide of China Medicine, vol. 8, no. 19, pp. 59-60, 2010.

[85] W. Y. Liu, F. Feng, C. X. Yu et al., "Qualitative and quantitative analysis of the main constituents of radix ilicis pubescentis by LC-coupled with DAD and ESI-MS detection," Natural Product Communications, vol. 5, no. 1, pp. 23-26, 2010.

[86] B. Wang, X. Liu, A. Zhou, M. Meng, and Q. Li, "Simultaneous analysis of coumarin derivatives in extracts of Radix Angelicae pubescentis (Duhuo) by HPLC-DAD-ESI-MSn technique," Analytical Methods, vol. 6, no. 19, pp. 7996-8002, 2014.

[87] W. X. Yang, "Divide the light intensity of light method to measurese Radix Angelcae Pubesentis inside the flavonoid's research," Science & Technology Information, vol. 26, p. 391, 2007.

[88] F. J. Dan, Z. J. Cai, J. H. Guo, J. R. Pan, and L. Wang, "Determination of total coumarins in Angelica Polymorpha maxim," Journal of China Three Gorges University, vol. 30, no. 6, pp. 91-93, 2008.

[89] L. Wang, H.-L. Wu, X.-L. Yin, Y. Hu, H.-W. Gu, and R.-Q. Yu, "Simultaneous determination of umbelliferone and scopoletin in Tibetan medicine Saussurea laniceps and traditional Chinese medicine Radix angelicae pubescentis using excitation-emission matrix fluorescence coupled with second-order calibration method," Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 170, pp. 104-110, 2017.

[90] L. Yang, A. J. Hou, Y. P. Sun, S. Wang, J. X. Zhang, and H. Jiang, "Screening and quantifying the quality markers of DuHuo by fingerprint modelling," Journal of Liquid Chromatography & Related Technologies, 2020.

[91] M. Ding, Y. Bai, J. Li et al., "A diol-based-matrix solid-phase dispersion method for the simultaneous extraction and determination of 13 compounds from Angelicae Pubescentis Radix by ultra high-performance liquid chromatography," Frontiers in Pharmacology, vol. 10, 2019.

[92] L. Jin, Q.-H. Zhang, J. He, E.-W. Liu, X.-M. Gao, and Y.-X. Chang, "An improved LC-MS/MS method for simultaneous determination of the eleven bioactive constituents for quality control of radix angelicae pubescentis and its related preparations," Scientific World Journal, vol. 2015, Article ID 365093, 10 pages, 2015.

[93] A. J. Hou and L. Yang, "A strategy for qualitative and quantitative profiling of Angelicae Pubescentis Radix and detection of its analgesic and anti-inflammatory components by spectrum-effect relationship and multivariate statistical analysis," Biomed. Chromatogr, p. e4910, 2020.

[94] X. Li, J. Wang, and L. Gao, "Anti-inflammatory and analgesic activity of R.A.P. (Radix angelicae pubescentis) ethanol extracts," African Journal of Traditional Complementary & Alternative Medicines, vol. 10, no. 3, pp. 422-426, 2013.

[95] L. Fan, L. Li, and H. F. He, "Pharmacological studies on antiinflammatory and analgesic effects of Radix angelicae pubeascentis's volatile oil," Anhui Medical and Pharmaceutical Journal, vol. 13, no. 2, pp. 133-134, 2009.

[96] H. S. Jin, "An Experimental Study on the Mechanism of Delaying Brain Aging with Radix Angelicae Pubescentis and its Alcohol Extract," Liaoning University of Traditional Chinese Medicine, Shenyang, China, 2001.

[97] S. Y. Chen, "Experimental Study of the Effects of Radix Angelicae Pubescentis on Malondialdehyde and Mitochondrial DNA Deletions in Naturally Aged Mice," Liaoning University of Traditional Chinese Medicine, Shenyang, China, 2005.

[98] X. Zou, R. P. Wang, H. Dai, and Y. Hu, "Experimental study on the antiangiogenic effect of radix angelicae pubescentis," Journal of Nanjing TCM University, vol. 24, no. 3, pp. 194-196, 2008.

[99] F. J. Dan, Z. J. Cai, L. B. Zhu, J. Z. Wang, and R. P. Zhang, "Studies of anti-gastric ulcer active fraction of Angelica polymorpha maxim," Journal of China Three Gorges University (Natural Sciences), vol. 30, no. 3, pp. 87-88, 2008.

[100] R. Li, C. Zhao, M. Yao, Y. Song, Y. Wu, and A. Wen, "Analgesic effect of coumarins from Radix angelicae pubescentis is mediated by inflammatory factors and TRPV1 in a spared nerve injury model of neuropathic pain," Journal of Ethnopharmacology, vol. 195, pp. 81-88, 2017.

[101] W. C. Sun, L. H. Yang, Y. Qiu, J. Ren, R. Huang, and J. Fu, "Identify nature N-acylethanolamide-hydrolyzing acid amide (NAAA) inhibitor: effect of Angelicae Pubescentis Radix on anti-inflammation," Journal of Chinese Materia Medica, vol. 36, no. 22, pp. 3161-3166, 2011.

[102] X. M. Ma, "Study on Antirheumatic Drugs for Effective Parts of Radix Angelicae Pubescentis," Liaoning University of Traditional Chinese Medicine, Shenyang, China, 2001.

[103] M. Li, J. H. Wen, F. Y. Ni et al., "Anti-inflammatory activity of two new sesquiterpenoids from Radix Angelicae Pubescentis," Acts Pharmaceutics Sinica, vol. 54, no. 2, pp. 343347, 2019.

[104] R. Z. Li, Q. Y. He, M. Qiao, R. J. Meng, L. P. Ge, and Y. Gu, "Study on the active components of Radix Angelicae Pubescentis against platelet aggregation and inhibition of experimental thrombosis," Journal of Beijing Medical University, vol. 19, no. 12, pp. 23-25, 1988.

[105] R. Z. Li, Q. Y. He, Q. B. Zhang, R. J. Meng, L. Y. Wang, and Y. Gu, "Study of the active ingredient of [gamma]-aminobutyric acid in radix angelicae pubescentis," Journal of Peking University (Health Sciences), vol. 21, no. 5, p. 376, 1989.

[106] W. L. Chen and Y. Lu, "Study on the promoting blood circulation to remove blood stasis action of Radix Angelicae Pubescentis ethanol extract," Inner Mongol Journal of Traditional Chinese Medicine, vol. 24, no. 57, pp. 6-7, 2001.

[107] Y. Pei, D. X. Li, and S. H. Sun, "Effects of Radix Angelicae Pubescentis and its alcohol extracts on apoptosis in brain tissue of naturally aged mice," Chinese Journal of Gerontology, vol. 25, no. 8, p. 959, 2005.

[108] Y. Pei, X. D. Ma, J. Yi, S. Li, S. Y. Wang, and J. Ma, "Effects of Radix Angelicae Pubescentis on antioxidant function and glutamate content in Parkinson's disease model rats," Chinese Journal of Gerontology, vol. 34, no. 5, pp. 1272-1274, 2014.

[109] Y.-F. Yang, W. Xu, W. Song, M. Ye, and X.-W. Yang, "Transport of twelve coumarins from angelicae pubescentis radix across a MDCK-pHaMDR cell monolayer-an in vitro model for blood-brain barrier permeability," Molecules, vol. 20, no. 7, pp. 11719-11732, 2015.

[110] H. Q. Li, D. X. Li, and S. H. Sun, "Changes of mtDNA-deficient respiratory chain enzyme complex and the mechanism of action of Radix Angelicae Pubescentis in aging mice," Chinese Archives of Traditional Chinese Medicine, vol. 24, no. 2, pp. 279-281, 2006.

[111] J. Zhang and W. B. Du, "Effects of Radix Angelicae Pubescentis on the p38MAPK signal transduction pathway in the brain of dementia rats," Chinese Journal of Gerontology, vol. 30, no. 11, pp. 1514-1515, 2010.

[112] Z. X. Yu, "Effects of Radix Angelicae Pubescentis ethanol extract on learning and memory ability and related enzymes in alzheimer's disease model mice," Chinese Community Physician, vol. 18, no. 12, p. 7, 2010.

[113] D. Zhao, X. D. Zhang, H. G. Hao et al., "Study on Neural Protective Function of DH Experimental Allergic Encephalomyelitis," Research and Practice on Chinese Medicines, vol. 27, no. 1, pp. 31-33, 2013.

[114] Y. H. Yan, "Effect and Mechanism of Osthole in Angelica Pubescens with NY-BM-SCs Transplantation in the Treatment of AD," Liaoning University of Traditional Chinese Medicine, Shenyang, China, 2017.

[115] Y. H. Yan, S. H. Li, L. Kong et al., "Neuroprotective effects of total coumarins in angelica pubescens against A[beta]-induced neurons damage," Liaoning Journal of Traditional Chinese Medicine, vol. 43, no. 8, pp. 1714-1717, 2016.

[116] Z. X. Zhang, "Studies on antifungal effect and compounds of Heracleam moellendorffii," Journal of Xianyang Normal University, vol. 22, no. 2, pp. 33-34, 2007.

[117] J. B. Qiu, Q. Xu, and X. H. Jiang, "Effects of ethanol extract of Angelicae Pubescentis Radix on cyclooxygenase," China Medical Herald, vol. 8, no. 16, pp. 42-43, 2011.

[118] R. J. Meng, Y. Gu, L. P. Ge, R. Z. Li, and Q. Y. He, "Effects of alcohol extract (H6F4) of Radix Angelicae Pubescentis on platelet aggregation and experimental thrombus formation," Chinese Traditional and Herbal Drugs, vol. 19, no. 12, pp. 23-25, 1988.

[119] Y. Huang, H. W. Wu, and Y. P. Wang, "Effect of intestinal absorption solution of Angelica pubescens on the tension of rat thoracic Aortic," Joumal of Basic Chinese Medicine, vol. 23, no. 2, pp. 187-190, 2017.

[120] J. Hu, L. Lin, X. P. Qian et al., "Experimental study of Angelica Pubescens and osthole isolated from Angelica Pubescens inhibiting angiogenesis in vitro," Journal Modern Oncology, vol. 21, no. 9, pp. 1945-1949, 2013.

[121] Y. Pei, J. Ma, S. Li et al., "Effect of radix angelicae pubescentis and coumarins CHOP and Caspasel2 in substantia nigra of rats with on expressions of Parkinson's disease," Chinese Archives of Traditional Chinese Medicine, vol. 37, no. 11, pp. 2579-2582, 2019.

[122] M. M. Li, J. H. Hu, L. He et al., "Isolation and identification of active compound from Radix Angelicae Biseratae extracts against citrus fungus pathogens," Journal of Fruit Science, vol. 29, no. 5, pp. 900-904, 2012.

[123] Y. C. Lu and X. M. Zhang, "Study on antioxidant effects on grease about radix angelicae pubesentis," Journal of Qinghai Junior Teachers' College, no. 5, pp. 74-76, 2004.

[124] L. Yao, H. X. Feng, H. Huo, B. Y. Liu, and N. Yu, "Pharmacological research review of osthole from DH," Chinese Archives of Traditional Chinese Medicine, vol. 30, no. 10, pp. 2221-2225, 2012.

[125] Z. H. Diao, "Two cases of radix angelicae pubescentis poisoning," Chinese Journal of Pediatrics, vol. 22, no. 5, p. 270, 1983.

[126] Z. H. Diao, "Two cases of duhuo poisoning," Chinese Journal of Pediatrics, vol. 22, no. 5, p. 270, 1984.

Liu Yang [ID], (1) Ajiao Hou, (1) Song Wang, (1) Jiaxu Zhang, (1) Wenjing Man, (1) Xinyue Guo, (1) Bingyou Yang [ID], (1) Hai Jiang [ID], (1) Haixue Kuang [ID], (1) and Qiuhong Wang [ID], (1,2)

(1) Key Laboratory of Chinese Materia Medica, Heilongjiang University of Chinese Medicine, Ministry of Education, Harbin 150040, China

(2) School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 528458, China

Correspondence should be addressed to Hai Jiang; jianghai_777@126.com, Haixue Kuang; hxkuang56@163.com, and Qiuhong Wang; qhwang668@sina.com

Received 2 May 2020; Revised 17 June 2020; Accepted 27 June 2020; Published 3 August 2020

Academic Editor: Simona Martinotti

Caption: FIGURE 1: The structures of coumarin compounds of AP.

Caption: FIGURE 2: The structures of organic acid compounds of AP.
TABLE 1: The prescription composition, dosage form, and
efficacy of AP.

Preparation
name                Main compositions     AP dosage   Formulation

Duhuo Jisheng        Radix Angelicae        54 g      Pill mixture
Wan                    Pubescentis                     decoction
Duhuo Jisheng         Taxilli Herba         98 g
Heji                Rehmanniae Radix        125 g
Duhuo Jisheng          Achyranthis
Tang                Bidentatae Radix
                     Asari Radix et
                    Rhizoma Gentianae
                   Macrophyllae Radix
                          Poria
                    Cinnamomi Cortex
                  Saposhnikoviae Radix
                   Chuanxiong Rhizoma
                    Codonopsis Radix
                  Glycyrrhizae Radix et
                         Rhizoma
                   Angelicae Sinensis
                          Radix
                    Eucommiae Cortex
                   Paeoniae Radix Alba
Duhuo Jiu            Radix Angelicae        200 g         Wine
                       Pubescentis
                  Saposhnikoviae Radix
                    Typhonii Rhizoma
                     Radix Angelicae       Unknown     Decoction
                       Pubescentis
Duhuo             Atractylodis Rhizoma
Cangzhu Tang      Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                   Chuanxiong Rhizoma

                     Radix Angelicae        25 g       Decoction
                       Pubescentis
                   Angelicae Sinensis
Duhuo Tang                Radix
                      Atractylodis
                      Macrocephalae
                         Rhizoma
                     Astragali Radix
                       Achyranthis
                    Bidentatae Radix
Duhuozi Tang         Radix Angelicae        500 g      Decoction
Yiwu                   Pubescentis
Duhuo Tang           Radix Angelicae        150 g      Decoction
Duhuo Xixin            Pubescentis
Tang
Duhuo San            Radix Angelicae                   Decoction
                       Pubescentis
                     Asari Radix et
                         Rhizoma
                   Chuanxiong Rhizoma
                        Gentianae
                   Macrophyllae Radix
                    Rehmanniae Radix
                  Saposhnikoviae Radix
                     Radix Angelicae        50 g         Pulvis
                       Pubescentis
                   Scutellariae Radix
                   Angelicae Sinensis
                          Radix
                   Chuanxiong Rhizoma
                  Rhei Radix et Rhizoma
                  Paeoniae Radix Rubra
                     Asari Radix et        Unknown      Ointment
                         Rhizoma
Tianhe             Paeoniae Radix Alba
Zhuifeng Gao         Radix Angelicae
                       Pubescentis
                  Paeoniae Radix Rubra
                   Angelicae Sinensis
                          Radix
                       Achyranthis
                    Bidentatae Radix
Tianma Wan         Gastrodiae Rhizoma       50 g          Pill
                     Radix Angelicae
                       Pubescentis
                       Achyranthis
                    Bidentatae Radix
                    Rehmanniae Radix
                    Eucommiae Cortex
                   Angelicae Sinensis
                          Radix
Tianma Qufeng       Rehmanniae Radix        50 g         Tablet
Bupian             Angelicae Sinensis
                          Radix

                     Radix Angelicae
                       Pubescentis
                    Eucommiae Cortex
                       Achyranthis
                    Bidentatae Radix
                          Poria
Zhonghua Dieda       Radix Angelicae       76.8 g         Pill
Wan                    Pubescentis
                     Cyperi Rhizoma
                    Cinnamomi Ramulus
                       Achyranthis
                    Bidentatae Radix
                    Eucommiae Cortex
                  Atractylodis Rhizoma
Zhengtian Wan      Angelicae Sinensis       102 g        Pill,
Zhengtian                 Radix                         capsule
Jiaonang           Paeoniae Radix Alba
                  Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                     Radix Angelicae
                       Pubescentis
                     Ephedrae Herba
Zhuanggu             Cibotii Rhizoma       Unknown        Pill
Guanjie Wan          Radix Angelicae
                       Pubescentis
                      Dipsaci Radix
                      Taxilli Herba
                    Rehmanniae Radix
                   Psoraleae Frsuctus
Wangbi Pian         Rehmanniae Radix       Unknown       Tablet
Wangbi Keli           Dipsaci Radix
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Rehmanniae Radix
                   Clematidis Radix et
                         Rhizoma
Guogong Jiu        Angelicae Sinensis      Unknown        Wine
                          Radix
                       Achyranthis
                    Bidentatae Radix
                     Radix Angelicae
                       Pubescentis
                   Paeoniae Radix Alba
                    Psoraleae Fructus
                  Saposhnikoviae Radix
Baidu San           Codonopsis Radix        100 g        Pulvis
                    Aurantii Fructus
                   Chuanxiong Rhizoma
                     Radix Angelicae
                       Pubescentis
                     Peucedani Radix
                     Bupleuri Radix
Goupi Gao         Saposhnikoviae Radix      20 g        Ointment
                     Ephedrae Herba
                   Angelicae Sinensis
                          Radix
                      Dipsaci Radix
                   Paeoniae Radix Alba
                     Radix Angelicae
                       Pubescentis
Fufang                 AGKISTRODON         Unknown       Tablet
Xiatianwu            Radix Angelicae
Pian                   Pubescentis
                   Clematidis Radix et
                         Rhizoma
                  Salviae Miltiorrhizae
                    Radix et Rhizoma
                       Achyranthis
                    Bidentatae Radix
Huoxue Zhitong     Paeoniae Radix Alba      5.4 g       Ointment
Gao                 Citri Reticulatae
                       Pericarpium
                   Angelicae Sinensis
                          Radix
                     Asari Radix et
                         Rhizoma
                   Schizonepetae Herba
                     Radix Angelicae
                       Pubescentis
Qufeng Zhitong        Dipsaci Radix         83 g         Pill,
Wan                Clematidis Radix et                  tablet,
Qufeng Zhitong           Rhizoma                        capsule
Pian                 Radix Angelicae
Qufeng Zhitong         Pubescentis
Jiaonang
Tongbi               Astragali Radix       4.42 g       Capsule
Jiaonang           Angelicae Sinensis
                          Radix
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Typhonii Rhizoma
                    Corydalis Rhizoma

Jisheng              Radix Angelicae       Unknown        Wine
Zhuifeng               Pubescentis
Jiu                    Achyranthis
                    Bidentatae Radix
                  Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                   Angelicae Sinensis
                          Radix
                          Poria
Shujin Wan           Strychni Semen          6 g          Pill
                     Ephedrae Herba
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Eucommiae Cortex
                      Dipsaci Radix
Shujin Huoluo         Taxilli Herba         30 g          Wine
Jiu                    Achyranthis
                    Bidentatae Radix
                   Angelicae Sinensis
                          Radix
                   Chuanxiong Rhizoma
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
Shufeng              Strychni Semen         30 g          Pill
Dingtong Wan           Achyranthis
                    Bidentatae Radix
                  Saposhnikoviae Radix
                     Radix Angelicae
                       Pubescentis
                     Ephedrae Herba
                    Eucommiae cortex
Yaobitong         Notoginseng Radix et     Unknown      Capsule
Jiaonang                 Rhizoma
                   Chuanxiong Rhizoma
                    Corydalis Rhizoma
                   Paeoniae Radix Alba
                       Achyranthis
                    Bidentatae Radix
                     Radix Angelicae
                       Pubescentis
Shexiang Qutong          Moschus             1 g        Aerosol
Qiwuji                Carthami Flos                     liniment
Shexiang Qutong      Radix Angelicae
Chaji                  Pubescentis
                    Rehmanniae Radix
                  Notoginseng Radix et
                         Rhizoma

Preparation                                Traditional and clinical
name                Main compositions                uses

Duhuo Jisheng        Radix Angelicae         Nourish blood, relax
Wan                    Pubescentis              tendon, dispel
Duhuo Jisheng                              wind, eliminate dampness,
Heji                                           and nourish liver
Duhuo Jisheng                              and kidney. It is used to
Tang                                         treat arthralgia and
                                            lumbago and knee pain.
                      Taxilli Herba
                    Rehmanniae Radix
                       Achyranthis
                    Bidentatae Radix
                     Asari Radix et
                    Rhizoma Gentianae
                   Macrophyllae Radix
                          Poria
                    Cinnamomi Cortex
                  Saposhnikoviae Radix
                   Chuanxiong Rhizoma
                    Codonopsis Radix
                  Glycyrrhizae Radix et
                         Rhizoma
                   Angelicae Sinensis
                          Radix
                    Eucommiae Cortex
                   Paeoniae Radix Alba
Duhuo Jiu            Radix Angelicae        Treatment of rheumatic
                       Pubescentis                joint pain.
                  Saposhnikoviae Radix
                    Typhonii Rhizoma
                     Radix Angelicae        Dissipate cold, relieve
                       Pubescentis                   pain.
Duhuo             Atractylodis Rhizoma
Cangzhu Tang      Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                   Chuanxiong Rhizoma
                     Radix Angelicae         Treatment of chronic
                       Pubescentis                limb pain.
                   Angelicae Sinensis
Duhuo Tang                Radix
                      Atractylodis
                      Macrocephalae
                         Rhizoma
                     Astragali Radix
                       Achyranthis
                    Bidentatae Radix
Duhuozi Tang         Radix Angelicae         Tonify and replenish
Yiwu                   Pubescentis             blood and kidney.
Duhuo Tang           Radix Angelicae        Treatment of postpartum
Duhuo Xixin            Pubescentis                  stroke.
Tang
Duhuo San            Radix Angelicae        Treat headaches caused
                       Pubescentis               by coldness.
                     Asari Radix et
                         Rhizoma
                   Chuanxiong Rhizoma
                        Gentianae
                   Macrophyllae Radix
                    Rehmanniae Radix
                  Saposhnikoviae Radix
                     Radix Angelicae        Treatment of all types
                       Pubescentis                of tumors.
                   Scutellariae Radix
                   Angelicae Sinensis
                          Radix
                   Chuanxiong Rhizoma
                  Rhei Radix et Rhizoma
                  Paeoniae Radix Rubra
                     Asari Radix et            Warm channel and
                         Rhizoma                expelling cold,
                                               disperse wind and
                                              eliminate dampness,
                                              and activate blood
                                               and relieve pain.
                                              Used for joint pain
                                               and limb numbness
                                                caused by wind,
                                                cold, dampness,
                                               and blood stasis.
Tianhe             Paeoniae Radix Alba
Zhuifeng Gao         Radix Angelicae
                       Pubescentis
                  Paeoniae Radix Rubra
                   Angelicae Sinensis
                          Radix
                       Achyranthis
                    Bidentatae Radix
Tianma Wan         Gastrodiae Rhizoma      Expel wind and eliminate
                                               dampness, dredge
                                            collateral and relieve
                                               pain, tonify and
                                              replenish liver and
                                               kidney. Used for
                                               rheumatic stasis
                                           resulting in numbness of
                                            limbs and pain in waist
                                                   and leg.
                     Radix Angelicae
                       Pubescentis
                       Achyranthis
                    Bidentatae Radix
                    Rehmanniae Radix
                    Eucommiae Cortex
                   Angelicae Sinensis
                          Radix
Tianma Qufeng       Rehmanniae Radix        Warm kidney nourishing
Bupian                                      the liver, dispel wind
                                           pain. Used for dizziness,
                                          tinnitus, joint pain, pain
                                            in waist and knee, and
                                            chills caused by liver
                                               and kidney loss,
                                                rheumatism and
                   Angelicae Sinensis       collateral penetration.
                          Radix
                     Radix Angelicae
                       Pubescentis
                    Eucommiae Cortex
                       Achyranthis
                    Bidentatae Radix
                          Poria
Zhonghua Dieda       Radix Angelicae           Detumescence and
Wan                    Pubescentis             analgesia, relax
                                             tendons and activate
                                            collaterals, hemostatic
                                             myosheng, invigorate
                                               blood, and remove
                                              blood stasis. Used
                                              for bruising bones,
                                             old and new bruising,
                                               trauma bleeding,
                                              rheumatic bruising.
                     Cyperi Rhizoma
                    Cinnamomi Ramulus
                       Achyranthis
                    Bidentatae Radix
                    Eucommiae Cortex
                  Atractylodis Rhizoma
Zhengtian Wan      Angelicae Sinensis       Expel wind and activate
Zhengtian                 Radix              blood, nourish blood
Jiaonang                                    and tonic liver, dredge
                                            collateral and relieve
                                             pain. It is used for
                                              migraines, tension
                                           headache, nerve headache,
                                           cervical spondylosis type
                                          headache, and premenstrual
                                              headache caused by
                                           external wind evil, blood
                                             stasis, blood loss of
                                          nutrition, hyperactivity of
                                                  liver yang.
                   Paeoniae Radix Alba
                  Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                     Radix Angelicae
                       Pubescentis
                     Ephedrae Herba
Zhuanggu             Cibotii Rhizoma         Tonify the liver and
Guanjie Wan                                  kidney, nourish blood
                                               and promote blood
                                              circulation, relax
                                           tendons and collaterals,
                                            regulate qi and relieve
                                              pain. Used for the
                                            treatment of arthritis,
                                             lumbar muscle strain,
                                                joint swelling,
                                                pain, numbness,
                                               limited movement.
                     Radix Angelicae
                       Pubescentis
                      Dipsaci Radix
                      Taxilli Herba
                    Rehmanniae Radix
                   Psoraleae Frsuctus
Wangbi Pian         Rehmanniae Radix         Tonify and replenish
Wangbi Keli                                    liver and kidney,
                                            strengthen tendons and
                                             bones. Disperse wind
                                             and dehumidification,
                                             dredge collateral and
                                             relax tendon. Used to
                                               treat rheumatoid
                                                  arthritis.
                      Dipsaci Radix
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Rehmanniae Radix
                   Clematidis Radix et
                         Rhizoma
Guogong Jiu        Angelicae Sinensis          Disperse wind and
                          Radix                dehumidification,
                                            relax sinew and dredge
                                           collateral. Used for the
                                           treatment of joint pain,
                                              adverse flexion and
                                           extension, hand and foot
                                            numbness, pain in waist
                                           and leg. It is also used
                                           for hemiplegia and askew
                                          caused by imbalance between
                                           channels and collaterals.
                       Achyranthis
                    Bidentatae Radix
                     Radix Angelicae
                       Pubescentis
                   Paeoniae Radix Alba
                    Psoraleae Fructus
                  Saposhnikoviae Radix
Baidu San           Codonopsis Radix          Relieving exterior
                                           syndrome by diaphoresis,
                                               disperse wind and
                                            dehumidification. Used
                                           to treat fever, headache,
                                           sore limbs, stuffy nose,
                                               cough and phlegm.
                    Aurantii Fructus
                   Chuanxiong Rhizoma
                     Radix Angelicae
                       Pubescentis
                     Peucedani Radix
                     Bupleuri Radix
Goupi Gao         Saposhnikoviae Radix         Disperse wind and
                                           dissipate cold, activate
                                            blood and relieve pain.
                                            Used for the treatment
                                           of limb numbness, lumbago
                                            and leg pain, or bruise
                                            injury, local swelling
                                                   and pain.
                     Ephedrae Herba
                   Angelicae Sinensis
                          Radix
                      Dipsaci Radix
                   Paeoniae Radix Alba
                     Radix Angelicae

                       Pubescentis
Fufang                 AGKISTRODON             Disperse wind and
Xiatianwu                                   dehumidification, relax
Pian                                            the tendons and
                                              collaterals, blood
                                             circulation and pain.
                                              It is used for the
                                              treatment of joint
                                              swelling pain, limb
                                           numbness, adverse flexion
                                           and rheumatoid arthritis,
                                              sciatica caused by
                                           obstruction of meridians
                                              and collaterals and
                                            rheumatic stasis block,
                                             sequelae of cerebral
                                                thrombosis and
                                                poliomyelitis.
                     Radix Angelicae
                       Pubescentis
                   Clematidis Radix et
                         Rhizoma
                  Salviae Miltiorrhizae
                    Radix et Rhizoma
                       Achyranthis
                    Bidentatae Radix
Huoxue Zhitong     Paeoniae Radix Alba        Activate blood and
Gao                                         relieve the pain. Used
                                             for the treatment of
                                             muscle and bone pain,
                                               muscle paralysis,
                                             resolve phlegm, joint
                                                     pain.
                    Citri Reticulatae
                       Pericarpium
                   Angelicae Sinensis
                          Radix
                     Asari Radix et
                         Rhizoma
                   Schizonepetae Herba
                     Radix Angelicae
                       Pubescentis
Qufeng Zhitong        Dipsaci Radix            Disperse wind and
Wan                                        dehumidification, tonify
Qufeng Zhitong                              and replenish liver and
Pian                                         kidney, strengthening
Qufeng Zhitong                              tendons and bones used
Jiaonang                                     for the treatment of
                                            joint swelling, lumbago
                                              and knee pain, limb
                                                   numbness.
                   Clematidis Radix et
                         Rhizoma
                     Radix Angelicae
                       Pubescentis
Tongbi               Astragali Radix           Disperse wind and
Jiaonang                                  dehumidification, activate
                                               blood and dredge
                                          collateral, dissipate cold
                                           and relieve pain, nourish
                                           and activate blood. Used
                                           for the treatment of cold
                                            joint pain, flexion and
                                             extension, rheumatoid
                                                  arthritis.
                   Angelicae Sinensis
                          Radix
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Typhonii Rhizoma
                    Corydalis Rhizoma
Jisheng              Radix Angelicae         Tonify and replenish
Zhuifeng               Pubescentis             liver and kidney,
Jiu                                            disperse wind and
                                               dehumidification,
                                             relieve pain. For the
                                              treatment of liver
                                                and kidney two
                                             deficient, wind cold
                                            dampness bi, waist and
                                            knee cold pain, flexion
                                                and extension,
                                             rheumatoid arthritis,
                                             lumbar muscle strain,
                                                    injury.
                       Achyranthis
                    Bidentatae Radix
                  Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                   Angelicae Sinensis
                          Radix
                          Poria
Shujin Wan           Strychni Semen            Disperse wind and
                                            dehumidification, relax
                                              tendon and activate
                                           blood. For the treatment
                                               of wind, cold and
                                             dampness, numbness of
                                            limbs, muscle and bone
                                           pain, walking difficult.
                     Ephedrae Herba
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Eucommiae Cortex
                      Dipsaci Radix
Shujin Huoluo         Taxilli Herba            Disperse wind and
Jiu                                            dehumidification,
                                              activate blood and
                                              dredge collateral,
                                            tonify yin and promote
                                               fluid production.
                                               Used for adverse
                                            flexion and extension,
                                             limb numbness, joint
                                              pain caused by yin
                                            deficiency, rheumatism
                                             blocking collateral,
                                                 blood stasis.
                       Achyranthis
                    Bidentatae Radix
                   Angelicae Sinensis
                          Radix
                   Chuanxiong Rhizoma
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
Shufeng              Strychni Semen            Disperse wind and
Dingtong Wan                               dissipate cold, activate
                                               blood and relieve
                                             pain. Used for joint
                                               pain, cold pain,
                                                stabbing pain,
                                              waist and leg pain
                                               and limb numbness
                                           caused by wind, cold and
                                            wet closure, and blood
                                            stasis. Local swelling
                                              caused by a bruise.
                       Achyranthis
                    Bidentatae Radix
                  Saposhnikoviae Radix
                     Radix Angelicae
                       Pubescentis
                     Ephedrae Herba
                    Eucommiae cortex
Yaobitong         Notoginseng Radix et        Activate blood and
Jiaonang                 Rhizoma            resolve stasis, dispel
                                              wind and eliminate
                                          dampness, move qi and stop
                                            pain. Used for lumbago
                                            caused by blood stasis
                                              and qi stagnation.

                   Chuanxiong Rhizoma
                    Corydalis Rhizoma
                   Paeoniae Radix Alba
                       Achyranthis
                    Bidentatae Radix
                     Radix Angelicae
                       Pubescentis
Shexiang Qutong          Moschus              Activate blood and
Qiwuji                                       resolve stasis, relax
Shexiang Qutong                               sinew and activate
Chaji                                        collateral, eliminate
                                                 swelling and
                                            relieve pain. Used for
                                               all kinds of fall
                                             injury, blood stasis
                                                swelling pain,
                                              rheumatism stasis,
                                                  joint pain.
                      Carthami Flos
                     Radix Angelicae
                       Pubescentis
                    Rehmanniae Radix
                  Notoginseng Radix et
                         Rhizoma

Preparation
name                Main compositions       Reference

Duhuo Jisheng        Radix Angelicae         Chinese
Wan                    Pubescentis        Pharmacopoeia
Duhuo Jisheng         Taxilli Herba
Heji                Rehmanniae Radix

Duhuo Jisheng          Achyranthis
Tang                Bidentatae Radix
                     Asari Radix et
                    Rhizoma Gentianae
                   Macrophyllae Radix
                          Poria
                    Cinnamomi Cortex
                  Saposhnikoviae Radix
                   Chuanxiong Rhizoma
                    Codonopsis Radix
                  Glycyrrhizae Radix et
                         Rhizoma
                   Angelicae Sinensis
                          Radix
                    Eucommiae Cortex
                   Paeoniae Radix Alba
Duhuo Jiu            Radix Angelicae       Qianjinfang
                       Pubescentis
                  Saposhnikoviae Radix
                    Typhonii Rhizoma
                     Radix Angelicae      Zhengyinmaizhi
                       Pubescentis
Duhuo             Atractylodis Rhizoma
Cangzhu Tang      Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                   Chuanxiong Rhizoma
                     Radix Angelicae       Huoyouxinshu
                       Pubescentis
                   Angelicae Sinensis
Duhuo Tang                Radix
                      Atractylodis
                      Macrocephalae
                         Rhizoma
                     Astragali Radix
                       Achyranthis
                    Bidentatae Radix
Duhuozi Tang         Radix Angelicae       Qianjinfang
Yiwu                   Pubescentis
Duhuo Tang           Radix Angelicae       Xiaopinfang
Duhuo Xixin            Pubescentis
Tang
Duhuo San            Radix Angelicae      Zhengyinmaizhi
                       Pubescentis
                     Asari Radix et
                         Rhizoma
                   Chuanxiong Rhizoma
                        Gentianae
                   Macrophyllae Radix
                    Rehmanniae Radix
                  Saposhnikoviae Radix
                     Radix Angelicae         Pujifang
                       Pubescentis
                   Scutellariae Radix
                   Angelicae Sinensis
                          Radix
                   Chuanxiong Rhizoma
                  Rhei Radix et Rhizoma
                  Paeoniae Radix Rubra
                     Asari Radix et          Chinese
                         Rhizoma          Pharmacopoeia
Tianhe             Paeoniae Radix Alba
Zhuifeng Gao         Radix Angelicae
                       Pubescentis
                  Paeoniae Radix Rubra
                   Angelicae Sinensis
                          Radix
                       Achyranthis
                    Bidentatae Radix
Tianma Wan         Gastrodiae Rhizoma        Chinese
                                          Pharmacopoeia
                     Radix Angelicae
                       Pubescentis
                       Achyranthis
                    Bidentatae Radix
                    Rehmanniae Radix
                    Eucommiae Cortex
                   Angelicae Sinensis
                          Radix
Tianma Qufeng       Rehmanniae Radix         Chinese
Bupian                                    Pharmacopoeia
                   Angelicae Sinensis
                          Radix
                     Radix Angelicae
                       Pubescentis
                    Eucommiae Cortex
                       Achyranthis
                    Bidentatae Radix
                          Poria
Zhonghua Dieda       Radix Angelicae         Chinese
Wan                    Pubescentis        Pharmacopoeia
                     Cyperi Rhizoma
                    Cinnamomi Ramulus
                       Achyranthis
                    Bidentatae Radix
                    Eucommiae Cortex
                  Atractylodis Rhizoma
Zhengtian Wan      Angelicae Sinensis        Chinese
Zhengtian                 Radix           Pharmacopoeia
Jiaonang           Paeoniae Radix Alba
                  Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                     Radix Angelicae
                       Pubescentis
                     Ephedrae Herba
Zhuanggu             Cibotii Rhizoma         Chinese
Guanjie Wan                               Pharmacopoeia
                     Radix Angelicae
                       Pubescentis
                      Dipsaci Radix
                      Taxilli Herba
                    Rehmanniae Radix
                   Psoraleae Frsuctus
Wangbi Pian         Rehmanniae Radix         Chinese
Wangbi Keli                               Pharmacopoeia
                      Dipsaci Radix
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Rehmanniae Radix
                   Clematidis Radix et
                         Rhizoma
Guogong Jiu        Angelicae Sinensis        Chinese
                          Radix           Pharmacopoeia
                       Achyranthis
                    Bidentatae Radix
                     Radix Angelicae
                       Pubescentis
                   Paeoniae Radix Alba
                    Psoraleae Fructus
                  Saposhnikoviae Radix
Baidu San           Codonopsis Radix         Chinese
                                          Pharmacopoeia
                    Aurantii Fructus
                   Chuanxiong Rhizoma
                     Radix Angelicae
                       Pubescentis
                     Peucedani Radix
                     Bupleuri Radix
Goupi Gao         Saposhnikoviae Radix       Chinese
                                          Pharmacopoeia
                     Ephedrae Herba
                   Angelicae Sinensis
                          Radix
                      Dipsaci Radix
                   Paeoniae Radix Alba
                     Radix Angelicae
                       Pubescentis
Fufang                 AGKISTRODON           Chinese
Xiatianwu                                 Pharmacopoeia
Pian                 Radix Angelicae
                       Pubescentis
                   Clematidis Radix et
                         Rhizoma
                  Salviae Miltiorrhizae
                    Radix et Rhizoma
                       Achyranthis
                    Bidentatae Radix
Huoxue Zhitong     Paeoniae Radix Alba       Chinese
Gao                                       Pharmacopoeia
                    Citri Reticulatae
                       Pericarpium
                   Angelicae Sinensis
                          Radix
                     Asari Radix et
                         Rhizoma
                   Schizonepetae Herba
                     Radix Angelicae
                       Pubescentis
Qufeng Zhitong        Dipsaci Radix          Chinese
Wan                                       Pharmacopoeia
Qufeng Zhitong     Clematidis Radix et
Pian                     Rhizoma

Qufeng Zhitong       Radix Angelicae
Jiaonang               Pubescentis
Tongbi               Astragali Radix         Chinese
Jiaonang                                  Pharmacopoeia
                   Angelicae Sinensis
                          Radix
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Typhonii Rhizoma
                    Corydalis Rhizoma
Jisheng              Radix Angelicae         Chinese
Zhuifeng               Pubescentis        Pharmacopoeia
Jiu                    Achyranthis
                    Bidentatae Radix
                  Saposhnikoviae Radix
                     Asari Radix et
                         Rhizoma
                   Angelicae Sinensis
                          Radix
                          Poria
Shujin Wan           Strychni Semen          Chinese
                                          Pharmacopoeia
                     Ephedrae Herba
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                    Eucommiae Cortex
                      Dipsaci Radix
                      Taxilli Herba
Shujin Huoluo                                Chinese
Jiu                                       Pharmacopoeia
                       Achyranthis
                    Bidentatae Radix
                   Angelicae Sinensis
                          Radix
                   Chuanxiong Rhizoma
                     Radix Angelicae
                       Pubescentis
                  Saposhnikoviae Radix
                     Strychni Semen
Shufeng                                      Chinese
Dingtong Wan                              Pharmacopoeia
                       Achyranthis
                    Bidentatae Radix
                  Saposhnikoviae Radix
                     Radix Angelicae
                       Pubescentis
                     Ephedrae Herba
                    Eucommiae cortex
                  Notoginseng Radix et
Yaobitong                Rhizoma             Chinese
Jiaonang                                  Pharmacopoeia
                   Chuanxiong Rhizoma
                    Corydalis Rhizoma
                   Paeoniae Radix Alba
                       Achyranthis
                    Bidentatae Radix
                     Radix Angelicae
                       Pubescentis
Shexiang Qutong          Moschus             Chinese
Qiwuji                                    Pharmacopoeia
Shexiang Qutong       Carthami Flos
Chaji                Radix Angelicae
                       Pubescentis
                    Rehmanniae Radix
                  Notoginseng Radix et
                         Rhizoma

TABLE 2: The coumarin compounds of AP.

No.                       Compounds                        Reference

1                  Acaculetindimethylether                   [43]
2                Angelicae lactone aldehyde-6                [43]
                  -formyl-7-methoxycoumarin
3                       Allimperatorin                       [43]

4                         Angelicin                          [43]
5                         Angelicone                         [43]
6                         Angelidiol                         [43]
7                          Angelin                           [43]
8                        Angelitriol                         [43]
9                         Angelmarin                         [43]
10                        Angelol A                          [43]
11                        Angelol B                          [43]
12                        Angelol C                          [43]
13                        Angelol D                          [43]
14                        Angelol E                          [43]
15                        Angelol F                          [43]
16                        Angelol G                          [43]
17                        Angelol H                          [43]
18                        Angelol I                          [43]
19                        Angelol J                          [43]
20                        Angelol K                          [43]
21                        Angelol L                          [43]
22                       Angenomalin                         [44]
23                      Angepubebisin                        [43]
24                    Anhydrobyakangelin                     [43]
25                        Anpubesol                          [43]
26                         Apaensin                          [43]
27                      Apiosylckimmin                       [43]
28                         Apterin                           [43]
29                        Bergapten                          [43]
30                        Bergaptol                          [43]
31                     Bisabolangelone                       [45]
32                      Byakangelicin                        [43]
33                      Byakangelicol                        [43]
34                         Cnidilin                          [43]
35                      Columbianetin                        [43]
36                      Columbianetin                        [43]
37                  Columbianetin acetate                    [43]
38          Columbianetin-[beta]-D-glucopyranoside           [43]
39                 Columbianetin propionate                  [45]
40                      Columbianadin                        [43]
41                       Coumurrayin                         [43]
42                    Dehydra-angelol A                      [39]
43                    Dehydra-angelol B                      [39]
44                    Dehydra-angelol C                      [39]
45                 2-Deoxymeranzin hydrate                   [44]
46                   Dihydrocolumbianadin                    [45]
47                         Ferulin                           [41]
48     8-(3-Hydroxylsoval-croyl-5,7-dimethoxycoumarin)       [43]
49     5-(2-Hydroxy-3-methoxy-3-methylbutoxy-psoralen)       [43]
50                       Imperatorin                         [43]
51                      Isoangenomalin                       [45]
52                        Isoanglol                          [43]
53                       Isobergapten                        [43]
54                      Isoimperatorin                       [43]
55                    Isooxypencedanine                      [43]
56                      Isopimpinellin                       [43]
57                       Isopsoralen                         [43]
58                        Marmesinin                         [43]
59                     Meranzin hydrate                      [43]
60              7-Methoxy-8-sene-cloylcoumarin               [43]
61                     Neobyakangelicol                      [43]
62                       Nodakenetin                         [45]
63                        Nodakenin                          [43]
64                         Osthenol                          [43]
65                          Osthol                           [43]
66                      Oxypeucedanin                        [43]
67                  Oxypeucedania hydrate                    [43]
68                        Pabulenol                          [43]
69                        Peucedanol                         [43]
70                         Psoralen                          [43]
71                        Scopoletin                         [43]
72                sec-O-Acetyl-byakangelicin                 [43]
73     sec-O-[beta]-D-Glucopy-ranosyl-(R)-byakangelicin      [41]
74    tert-O-[beta]-D-Glucopy-ranosyl-(R)-byakangelicin      [41]
75                        Ulopterol                          [43]
76                      Umbelliferone                        [43]
77                      Umbelliprenin                        [43]
78                        Vaginidiol                         [43]
79                       Xanthotoxin                         [43]

TABLE 3: The volatile oils compounds of AP.

No.                      Compounds                       Reference

1                        Acorenone                         [61]
2                        Aristolene                        [49]
3            Benzene-1-methyl-2-(1-methylethyl)            [49]
4                 Benzene-2-methoxy                        [49]
                -4-methyl-1-(1-methylethyl)
5              Benzene-1,2,4-trimethoxy                    [49]
                      -5-(1-proprnyl))
6                   [alpha]-Bergamotene                    [43]
7                Bicyclo-[3, 10]-hexan-3-ol                [49]
8              Bicycol [7, 2, 0]undec-4-ene,               [43]
               4,11,11-trimethyl-8-methylene
9                    [alpha]-Bisabolene                    [43]
10                   [beta]-Bisabolene                     [43]
11                        Camphene                         [44]
12                   [beta]-Camphenone                     [49]
13                        3-Carene                         [48]
14                         Cedrol                          [49]
15                    [alpha]-Copaene                      [43]
16                        p-Cresol                         [43]
17                      Cyclohexene                        [49]
18               [alpha]-Cyclohexyl decane                 [43]
19               1,3-Cyclohexadiene-5-(1,5                 [43]
                -dimethyl-4-hexenyl-2-methyl
20                  (+)-Cycloisosativene                   [49]
21            2-Cyclopropen-1-one,2,3-diphenyl             [43]
22                      Decylacetate                       [44]
23              [s-(R, s)]-3-(1,5 Dimethyl-4               [44]
              -hexene)-6-methylene-cyclohexene
24                   3,6-Dimethyloctane                    [49]
25             2,2-Dimethyl-8-oxo-3,4-dihydro              [50]
          -2H,8H-pyrano[3,2-g] chromen-3-yl ester
26              8,8-Dimethyl-2-oxo-2,8,9,10                [50]

       -tetrahydropyrano(2,3-f)chromene-9,10-diylbis
27                5,6-Dimethyl-3a,4,7,7a-H                 [43]
28                    [alpha]-Elemene                      [43]
29                     [beta]-Elemene                      [43]
30                         Elemol                          [50]
31                        Elixene                          [43]
32                      Eremophilene                       [43]
33      [1S-(1[alpha], 2[beta], 4[beta])]-1-Ethenyl        [44]
       -1-methyl-2,4-bis-(1-methyethenyl)-cyclohexane
34                   [alpha]-Funebrene                     [43]
35                        Globulol                         [49]
36                         Guaiol                          [43]
37                    [beta]-Gurjunene                     [50]
38                   (Z)-7-Hexadecenal                     [49]
39                     1-Hexadecanol                       [50]
40                       3-Hexanol                         [44]
41                        Humulene                         [43]
42              4-Hydroxy-3-methylacetophenone             [47]
43             1,3-Isobenzafurandione,3a,4,7,              [51]
                 7a-tetrahydro-5,6-dimethyl
44     Isoprop[gamma]-4-methylene-7-methyl-1, 2, 3,4,      [43]
             4A, 5. 6, 8A-octahydronaphthalene
45                     Isosericenine                       [43]
46                         Ledol                           [49]
47      Leecanoic acid,2,4,6-trirnethyl-methyl ester       [43]
48                    Lignoceric acid                      [51]
49                       d-Limonene                        [48]
50                     4-Longifolene                       [49]
51                  [alpha]-Longipinene                    [43]
52        4-Methoxy-6-(2-propenyl)-1,3-benzodioxole        [49]
53                 4-Methoxyacetophenone                   [43]
54                   8-Methyl-1-decene                     [44]
55               3-Methyl-but-2-enoic acid                 [50]
56                  4-Methylclohexanone                    [43]
57              1-Methyl-1,4-cyclohexadiene                [44]
58             4-Methylene-1-(1-methylethyl)               [44]
                 -bicyclo [3, 1, 0] hexane
59             4-Methylene-1-(1-methylethyl)               [44]
                -bicyclo [3, 1, 0] hex-2-ene
60                   4-Methylene-1,5,5                     [44]
                   -trimethylcyclohecene
61     4,4'-Methylenebis[2,3,5,6-tetremethyl] phenol       [43]
62       2-[1-Methylethyl-methylcarbam ate] phenol         [49]
63        2-Methyl-1-methylene-3-(1-methylethenyl)         [44]
                       -cyclopentane
64           2-Methyl-5-(1-methylethyl)-phenol             [49]
65                     3-Methylnolane                      [43]
66                     2-Methyloctane                      [43]
67                     o-Methylphenol                      [49]
68                  9-Methyl-1-undecene                    [49]
69                  10-Methyl-1-undecene                   [49]
70                        Myrcene                          [43]
71                        Myrtenal                         [43]
72       Naphthalene-1,2,3,4,4[alpha],5,6,8[alpha]         [43]
             -octahydro-7-methyl-4-methylene-1
                 -(1-methylethyl)-(1,4a,8a)
73                     Naphthalenone                       [49]
74                       Nerolidol                         [43]
75                        n-Nonane                         [43]
76                        n-Octane                         [43]
77                       n-Undecane                        [43]
78         9,12-Octadecadienoic acid methyl ester          [49]
79                        o-Cymene                         [47]
80                         Osthol                          [43]
81           Oxacyclohexadecan-[alpha]-one                 [43]
82                  [gamma]-Patchoulene                    [43]
83                        p-Cresol                         [51]
84                        p-Cymene                          [9]
85              7, 10-Pentadecadiynoic acid                [43]
86            1-Penten-3-one thyl vinyl ketone             [43]
87                     Pentylbenzene                       [49]
88                       Peucedanol                        [43]
89         Phenol,4-(1,1-dimethylethyl)-2-methyl           [43]
90                  [alpha]-Phellandrene                   [43]
91                     [alpha]-Pinene                      [43]
92                     [beta]-Pinene                       [43]
93                    [alpha]-Selinene                     [47]
94               [beta]-Sesquiphellandrene                 [47]
95                      Sylvestrene                        [43]
96                   [alpha]-Terpinene                     [43]
97                     1-Tetradecene                       [43]
98           1,5,5,8-Tetramethyl-12-oxabicyclo             [44]
                 [9, 1, 0] dodeca-3,7-diene
99             Thalic acid diisobuthyl ester               [49]
100                        Thymol                          [43]
101                       Toluene                          [49]
102               trans-p-Menth-2-en-7-ol                  [51]
103               3, 7, 11-Tridecatrienoic                 [43]
              acid,4,8,12-trimethl-ester[Z,E]
104                1,7,7-Trimethylbicyclo                  [50]
                 -[2.2.1]-hept-2-yl-acetate
105                2,4,6-Trimethylmethyl                   [43]
                    ester-decanoic acid
106               1,3,3-Trimethyl-tricyclo                 [44]
                    [2.2.1.02,6] heptane
107           7[alpha]-Twtrahydro-5,6-dimethyl             [43]
108                      Ulopterol                         [43]
109                     Zingiberene

TABLE 4: The organic acid compounds of AP.

No.                  Compounds                  Reference

1                  Caffeic acid                   [43]
2             3-O-Caffeoylquinic acid             [71]
3             4-O-Caffeoylquinic acid             [71]
4             5-O-Caffeoylquinic acid             [71]
5                  Ferulic acid                   [71]
6            1,5-Dicaffeoylquinic acid            [71]
7            3,4-Dicaffeoylquinic acid            [71]
8            3,5-Dicaffeoylquinic acid            [71]
9            4,5-Dicaffeoylquinic acid            [71]
10                Isoferulic acid                 [44]
11    [2,3,4,9-Tetrahydro-1H-pyrido-(3,4-b)]      [71]
           -indole-3-(ar-boxy-lic acid)
12        3-O-trans-Coumaroylquinic acid          [44]
13         3-O-trans-Feruloylquinic acid          [44]

TABLE 5: The pharmacology of AP.

Effects            Extract/compound dose        Animal/cell line

Anti-                 1.5 g/kg (40%,          Xylene-induced mice
inflammatory         60%, 80%) ethanol             ears edema
effect               extract solution          Egg white-induced
                                            mice pettitoes swelling
                                               Tampon granulation
                                             -induced mice swelling
                    0.4 mL 50% ethanol        Xylene-induced mice
                     extract solution              ears edema
                                              Carrageenan-induced
                                                 mice swelling
                    0.15 and 0.29 g/kg       Egg white-induced rat
                    volatile oil of AP         pettitoes swelling
                  AP 95% ethanol extract        LPS-induced rat
                    solution (0.1 g/L,       peritoneal macrophages
                      1 g/L, 10 g/L)
                    Volatile oil of AP       LPS-induced RAW 264.7
                    (10 mg/L, 50 mg/L,                cell
                         250 mg/L)
                     Angesesquid A and      Primary chondrocytes of
                       angesesquid B        rat intervertebral disc
                    1.5 g/kg (40%, 60%,     Acetic acid-induced and

                   80%) ethanol extract      tail-immersion-induced
                         solution                   writhing
                    0.4 mL 50% ethanol      Hot plate, acetic acid,
                     extract solution         and formalin-induced
                                                      pain
Analgesic           0.15 and 0.29 g/kg       Hot plate, acetic acid
                    volatile oil of AP         -induced mice pain
                      Coumarins in AP         Spared nerve injury
                                                   model rat
                     0.4 g/kg, 1.0g/kg          ADP-induced mice
                    AP ethanol extract        platelet aggregation
                       10 mg/kg GABA          Multiple arrhythmia
                                                     models
Cardiovascular      AP ethanol extract       Patients with vertigo
effect               1.28 g/ml AP 95%        Thoracic aortic rings
                      ethanol extract               in rats
                   3.75-30 ([micro]g/ml       Human umbilical vein
                      AP 95% ethanol               endothelia
                    extract and osthol         Human colon cancer
                                                      cell
                  AP 90% ethanol extract      D-Galactose-induced
                     (2.7 g/kg/d, 8.1           mice aging model
                   g/kg/d, 24.3 g/kg/d)
                   12ml/kg/d AP alcohol            Aged mice
                    extract or AP water
                          extract
                    Coumarin in AP with       Lactacystin-induced
                   22.05 mg/kg/ d, 66.15          PD rat model
                  mg/kg/d, 198.45 mg/kg/d
                   Coumarin in AP with 3      Lactacystin-induced
                    g/kg/d AP granules            PD rat model
                         3 g/kg/d
                   Compound AP granules
Neuroprotective   AP 90% ethanol extract      Mice aged 16 months
effect               or water extract
                        (18 g/kg/d)
                   2 ml/mouse AP extract      A[beta]-induced rat
                                                 dementia model
                     1 g/kg or 4 g/kg        D-Galactose or sodium
                    AP ethanol extract          nitrite-induced
                                            Alzheimer's disease mice
                      20mg/ml osthol             APP/PS1 double
                                                transgenic mice
                       10-250 mg/ml           A[beta]-induced mice
                      coumarin in AP           nerve injury model
                    9, 18, 36 ng/kg AP          MOG35-55 peptide
                          extract            fragment-induced mice
                                                   EVE model
Antibacterial       AP petroleum ether               Fungus
effect                    extract
                     1 g/L AP ethanol         Penicillium italicum
                          extract            Penicillium digitatum
                                                 Colletotrichum
                                                gloeosporioides
                   12ml/kg/d AP alcohol            Aged mice
                        extract or
                     AP water extract
Antioxidation       1 g/kg or 4 g/kg AP      D-Galactose or sodium
effects               ethanol extract           nitrite-induced
                                            Alzheimer's disease mice
                       0.4 ml AP 50%        Carrageenan-induced mice
                      ethanol extract               swelling
Antitumor           0.3125-10 mg/ml AP          HMVECs SMMC-7721
effect               aqueous solution
Antigastric             Chloroform,             Aspirin-ethanol
ulcer              petroleum ether, and      solution-induced mice
                       ethyl acetate          gastric ulcer model
                      extracts of AP

Effects            Extract/compound dose    Study design

Anti-                 1.5 g/kg (40%,          In vivo
inflammatory         60%, 80%) ethanol
effect               extract solution
                    0.4 mL 50% ethanol        In vivo
                     extract solution
                    0.15 and 0.29 g/kg        In vivo
                    volatile oil of AP
                  AP 95% ethanol extract      In vitro
                    solution (0.1 g/L,
                      1 g/L, 10 g/L)
                    Volatile oil of AP        In vitro
                    (10 mg/L, 50 mg/L,
                         250 mg/L)
                     Angesesquid A and        In vitro
                       angesesquid B
                    1.5 g/kg (40%, 60%,       In vivo
                   80%) ethanol extract
                         solution
                    0.4 mL 50% ethanol        In vivo
                     extract solution
Analgesic           0.15 and 0.29 g/kg        In vivo
                    volatile oil of AP
                      Coumarins in AP         In vivo
                     0.4 g/kg, 1.0g/kg        In vivo
                    AP ethanol extract
                       10 mg/kg GABA          In vivo
Cardiovascular      AP ethanol extract        In vivo
effect               1.28 g/ml AP 95%         In vitro
                      ethanol extract
                   3.75-30 ([micro]g/ml       In vitro
                      AP 95% ethanol
                    extract and osthol
                  AP 90% ethanol extract      In vivo
                     (2.7 g/kg/d, 8.1
                   g/kg/d, 24.3 g/kg/d)
                   12ml/kg/d AP alcohol       In vivo
                    extract or AP water
                          extract
                    Coumarin in AP with       In vivo
                   22.05 mg/kg/ d, 66.15
                  mg/kg/d, 198.45 mg/kg/d
                   Coumarin in AP with 3      In vivo
                    g/kg/d AP granules
                         3 g/kg/d
                   Compound AP granules
Neuroprotective   AP 90% ethanol extract      In vivo
effect               or water extract
                        (18 g/kg/d)
                   2 ml/mouse AP extract      In vivo
                     1 g/kg or 4 g/kg         In vivo
                    AP ethanol extract
                      20mg/ml osthol          In vivo
                       10-250 mg/ml           In vivo
                      coumarin in AP
                    9, 18, 36 ng/kg AP        In vivo
                          extract
Antibacterial       AP petroleum ether        In vitro
effect                    extract
                     1 g/L AP ethanol         In vitro
                          extract
                   12ml/kg/d AP alcohol       In vivo
                        extract or
                     AP water extract
Antioxidation       1 g/kg or 4 g/kg AP       In vivo
effects               ethanol extract
                       0.4 ml AP 50%          In vivo
                      ethanol extract
Antitumor           0.3125-10 mg/ml AP        In vitro
effect               aqueous solution
Antigastric             Chloroform,           In vivo
ulcer              petroleum ether, and
                       ethyl acetate
                      extracts of AP

Effects            Extract/compound dose         Control

Anti-                 1.5 g/kg (40%,             Aspirin
inflammatory         60%, 80%) ethanol
effect               extract solution
                    0.4 mL 50% ethanol           Aspirin
                     extract solution
                    0.15 and 0.29 g/kg         Hexadecadrol
                    volatile oil of AP
                  AP 95% ethanol extract        Celecoxib
                    solution (0.1 g/L,         Indomethacin
                      1 g/L, 10 g/L)               DMSO
                    Volatile oil of AP             None
                    (10 mg/L, 50 mg/L,
                         250 mg/L)
                     Angesesquid A and             None
                       angesesquid B
                    1.5 g/kg (40%, 60%,          Aspirin
                   80%) ethanol extract
                         solution
                    0.4 mL 50% ethanol           Aspirin
                     extract solution
Analgesic           0.15 and 0.29 g/kg       Aspirin Morphine
                    volatile oil of AP        hydrochloride
                      Coumarins in AP            Morphine
                     0.4 g/kg, 1.0g/kg            Black
                    AP ethanol extract
                       10 mg/kg GABA              Black
Cardiovascular      AP ethanol extract       Compound Danshen
effect               1.28 g/ml AP 95%             CaCl2
                      ethanol extract
                   3.75-30 ([micro]g/ml            None
                      AP 95% ethanol
                    extract and osthol
                  AP 90% ethanol extract          Model
                     (2.7 g/kg/d, 8.1
                   g/kg/d, 24.3 g/kg/d)
                   12ml/kg/d AP alcohol           Black
                    extract or AP water
                          extract
                    Coumarin in AP with     Madopar, ibuprofen
                   22.05 mg/kg/ d, 66.15
                  mg/kg/d, 198.45 mg/kg/d
                   Coumarin in AP with 3    Madopar, celecoxib
                    g/kg/d AP granules
                         3 g/kg/d
                   Compound AP granules
Neuroprotective   AP 90% ethanol extract          Water
effect               or water extract
                        (18 g/kg/d)
                   2 ml/mouse AP extract       Indometacin
                     1 g/kg or 4 g/kg             Water
                    AP ethanol extract
                      20mg/ml osthol               None
                       10-250 mg/ml                None
                      coumarin in AP
                    9, 18, 36 ng/kg AP      Prednisone acetate
                          extract
Antibacterial       AP petroleum ether             None
effect                    extract
                     1 g/L AP ethanol              None
                          extract
                   12ml/kg/d AP alcohol           Black
                        extract or
                     AP water extract
Antioxidation       1 g/kg or 4 g/kg AP           Water
effects               ethanol extract
                       0.4 ml AP 50%             Aspirin
                      ethanol extract
Antitumor           0.3125-10 mg/ml AP       Cyclophosphamide
effect               aqueous solution
Antigastric             Chloroform,             Cimetidine
ulcer              petroleum ether, and
                       ethyl acetate
                      extracts of AP

Effects            Extract/compound dose       Mechanism/results

Anti-                 1.5 g/kg (40%,           By inhibiting the
inflammatory         60%, 80%) ethanol         activity of NAAA,
effect               extract solution       intracellular biological
                                             activity was increased
                                                and the level of
                                            proinflammatory factors
                                                 was decreased.
                    0.4 mL 50% ethanol          It plays an anti
                     extract solution        -inflammatory role by
                                              reducing the levels
                                            of inflammatory factors
                                                such as MDA and
                                                  TNF-[alpha].
                    0.15 and 0.29 g/kg          It plays an anti
                    volatile oil of AP       -inflammatory role by
                                             inhibiting the release
                                            of inflammatory factors
                                                 such as 5-HT.
                  AP 95% ethanol extract     AP inhibited COX-1 and
                    solution (0.1 g/L,          COX-2 in varying
                      1 g/L, 10 g/L)         degrees, and there was
                                                a dose-response
                                                 relationship.
                    Volatile oil of AP         By inhibiting the
                    (10 mg/L, 50 mg/L,        hydrolysis activity
                         250 mg/L)            of NAAA and increase
                                              the level of N-PEA,
                                               downregulating the
                                                 expression of
                                               TNF-[alpha], iNOS,
                                                 IL-6 mRNA, and
                                                 inhibiting the
                                                   release of
                                              TNF-[alpha] and NO.
                     Angesesquid A and          Inflammation is
                       angesesquid B        inhibited by inhibiting
                                               the release of NO.
                    1.5 g/kg (40%, 60%,        By inhibiting the
                   80%) ethanol extract      activity of NAAA, the
                         solution           intracellular biological
                                             activity was increased
                                                and the level of
                                              inflammatory factors
                                             was reduced to play an
                                                analgesic role.
                    0.4 mL 50% ethanol      By inhibiting the level
                     extract solution       of MDA and inflammatory
                                             factors was reduced to
                                            play an analgesic role.
Analgesic           0.15 and 0.29 g/kg        AP has an analgesic
                    volatile oil of AP       effect similar to that
                                              of nSAID rather than
                                              narcotic analgesics.
                      Coumarins in AP         AP has the analgesic
                                            effect mainly related to
                                                  reducing the
                                                concentration of
                                                proinflammatory
                                                   cytokines
                                                of TNF-[alpha],
                                              IL-1[beta], and IL-6
                                                and reducing the
                                              expression of TRPV1
                                            and perk in the damaged
                                                    neurons.
                     0.4 g/kg, 1.0g/kg       AP alcohol extract can
                    AP ethanol extract        shorten the thrombus
                                             length and prolong the
                                            tail hemorrhage time of
                                                mice to inhibit
                                              ADP-induced platelet
                                              aggregation in mice.
                       10 mg/kg GABA         GABA could prolong the
                                             start time, reduce the
                                                  incidence of
                                                  ventricular
                                              tachycardia, shorten
                                                the duration of
                                                  ventricular
                                            tachycardia, reduce the
                                            mortality of ventricular
                                            fibrillation, reduce APA
                                              and AP050 and AP090.
Cardiovascular      AP ethanol extract       By reducing the whole
effect                                      blood viscosity, plasma
                                            viscosity and red blood
                                             cell aggregation index
                                              of vertigo patients,
                                            increasing the cerebral
                                            blood flow speed to play
                                             the role of promoting
                                             blood circulation and
                                                removing stasis.
                     1.28 g/ml AP 95%       AP had a good diastolic
                      ethanol extract        effect on vasoconstric
                                               -tion caused by PE
                                                and KCl, and its
                                             mechanism was related
                                                to the influx of
                                                 Ca[Cl.sub.2].
                   3.75-30 ([micro]g/ml          Inhibition of
                      AP 95% ethanol            angiogenesis by
                    extract and osthol           stagnation of
                                               endothelial cycle
                                                mainly in G0-G1.
                  AP 90% ethanol extract      AP's delay of brain
                     (2.7 g/kg/d, 8.1         aging is associated
                   g/kg/d, 24.3 g/kg/d)      with anti-free radical
                                                peroxide damage,
                                                  reduction of
                                              immunosuppression of
                                                arachidonic acid
                                                metabolites, and
                                              antagonism of brain
                                                 inflammation.
                   12ml/kg/d AP alcohol       AP could reduce the
                    extract or AP water      content of MDA content
                          extract             and the deletion of
                                            DNA fragment in natural
                                                  aging mice.
                    Coumarin in AP with       Inhibition of lipid
                   22.05 mg/kg/ d, 66.15     peroxidation in serum
                  mg/kg/d, 198.45 mg/kg/d      and brain tissue,
                                            increase of antioxidant
                                              enzyme activity, and
                                             decrease of excitatory
                                             amino acid Glu content
                                               in serum and brain
                                                    tissue.
                   Coumarin in AP with 3     Coumarin in AP and AP
                    g/kg/d AP granules         may protect PD by
                         3 g/kg/d            inhibiting endoplasmic
                   Compound AP granules        reticulum stress.
Neuroprotective   AP 90% ethanol extract       It can improve the
effect               or water extract             activity of
                        (18 g/kg/d)              mitochondrial
                                               respiratory chain
                                                enzymes complex
                                                I and IV in the
                                             brain of aged mice and
                                             protect the oxidative
                                            damage of mitochondrial
                                                  DNA in mice.
                   2 ml/mouse AP extract       AP can inhibit the
                                             expression of P38 MAPK
                                                in rat brain and
                                                  improve the
                                              learning and memory
                                              ability of dementia
                                                  model rats.
                     1 g/kg or 4 g/kg           AP can delay the
                    AP ethanol extract           occurrence of
                                              Alzheimer's disease
                                               by increasing SOD
                                               and reducing AChE
                                                in brain tissue.
                      20mg/ml osthol         Osthol can promote the
                                              survival of NT-3-BM
                                             -NSCs and enhance the
                                               cholinergic nerve
                                             function in the brain.
                       10-250 mg/ml             By promoting the
                      coumarin in AP         expression of CREB and
                                              BDNF, the expression
                                             of P-CREB and BDNF is
                                              increased to play a
                                             neuroprotective role.
                    9, 18, 36 ng/kg AP          It can alleviate
                          extract            demyelination injury,
                                             inhibit the secretion
                                               of proinflammatory
                                              cytokines by spleen
                                              lymphocytes, and has
                                            neuroprotective effect.
Antibacterial       AP petroleum ether        AP essential oil has
effect                    extract             different degree of
                                             bacteriostatic effect
                                              on different fungi.
                     1 g/L AP ethanol          Isobergamolactone,
                          extract            sphondin, pimpinellin,
                                             and isopimpinellin in
                                            AP showed antibacterial
                                                   activity.
                   12ml/kg/d AP alcohol       AP could reduce the
                        extract or            level of MDA in the
                     AP water extract        brain tissues of mice.
Antioxidation       1 g/kg or 4 g/kg AP        AP could delay the
effects               ethanol extract            occurrence of
                                             Alzheimer's disease by
                                              increasing the level
                                                    of SOD.
                       0.4 ml AP 50%           AP alcohol extract
                      ethanol extract          could inhibit the
                                              concentration of MDA
                                              with the inhibitory
                                                rate of 23.49%.
Antitumor           0.3125-10 mg/ml AP         AP can inhibit the
effect               aqueous solution           proliferation of
                                              human microvascular
                                               endothelial cells.
                                                 Inhibition of
                                                 angiogenesis.
Antigastric             Chloroform,           The fat-soluble part
ulcer              petroleum ether, and           of AP is the
                       ethyl acetate         effective part against
                      extracts of AP             gastric ulcer.

Effects            Extract/compound dose     Ref

Anti-                 1.5 g/kg (40%,        [93]
inflammatory         60%, 80%) ethanol
effect               extract solution
                    0.4 mL 50% ethanol      [92]
                     extract solution
                    0.15 and 0.29 g/kg      [94]
                    volatile oil of AP
                  AP 95% ethanol extract    [99]
                    solution (0.1 g/L,
                      1 g/L, 10 g/L)
                    Volatile oil of AP      [100]
                    (10 mg/L, 50 mg/L,
                         250 mg/L)
                     Angesesquid A and      [101]
                       angesesquid B
                    1.5 g/kg (40%, 60%,     [93]
                   80%) ethanol extract
                         solution
                    0.4 mL 50% ethanol      [92]
                     extract solution
Analgesic           0.15 and 0.29 g/kg      [94]
                    volatile oil of AP
                      Coumarins in AP
                                           [94]
                     0.4 g/kg, 1.0g/kg      [103]
                    AP ethanol extract
                       10 mg/kg GABA        [104]
Cardiovascular      AP ethanol extract      [105]
effect               1.28 g/ml AP 95%       [106]
                      ethanol extract
                   3.75-30 ([micro]g/ml     [11]
                      AP 95% ethanol
                    extract and osthol
                  AP 90% ethanol extract    [95]
                     (2.7 g/kg/d, 8.1
                   g/kg/d, 24.3 g/kg/d)
                   12ml/kg/d AP alcohol     [96]
                    extract or AP water
                          extract
                    Coumarin in AP with     [107]
                   22.05 mg/kg/ d, 66.15
                  mg/kg/d, 198.45 mg/kg/d
                   Coumarin in AP with 3    [108]
                    g/kg/d AP granules
                         3 g/kg/d
                   Compound AP granules
Neuroprotective   AP 90% ethanol extract    [109]
effect               or water extract
                        (18 g/kg/d)
                   2 ml/mouse AP extract    [110]
                     1 g/kg or 4 g/kg       [111]
                    AP ethanol extract
                      20 mg/ml osthol       [112]
                       10-250 mg/ml         [113]
                      coumarin in AP
                    9, 18, 36 ng/kg AP      [114]
                          extract
Antibacterial       AP petroleum ether      [115]
effect                    extract
                     1 g/L AP ethanol       [116]
                          extract
                   12 ml/kg/d AP alcohol    [96]
                        extract or
                     AP water extract
Antioxidation       1 g/kg or 4 g/kg AP     [111]
effects               ethanol extract
                       0.4 ml AP 50%        [92]
                      ethanol extract
Antitumor           0.3125-10 mg/ml AP      [97]
effect               aqueous solution
Antigastric             Chloroform,         [98]
ulcer              petroleum ether, and
                       ethyl acetate
                      extracts of AP
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Author:Yang, Liu; Hou, Ajiao; Wang, Song; Zhang, Jiaxu; Man, Wenjing; Guo, Xinyue; Yang, Bingyou; Jiang, Ha
Publication:Evidence - Based Complementary and Alternative Medicine
Geographic Code:9CHIN
Date:Aug 31, 2020
Words:17898
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