Study on the inhibitory effects of Korean medicinal plants and their main compounds on the 1,1-diphenyl-2-picrylhydrazyl radical.
A 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-generating system was used to evaluate the antioxidant properties of Korean medicinal plants that have been used widely as folk medicines for several disorders, as well as compounds isolated from them. Among the Rosaceae, Rosa rugosa and Rosa davurica showed strong DPPH radical-scavenging activity. The most effective medicinal plant from families other than Rosaceae was Cedrela sinensis, followed in order by Nelumbo nucifera, Eucommia ulmoides, Zanthoxylum piperitum, Cudrania tricuspidata and Houttuynia cordata. These results serve as a good index of the free radical-scavenging activities of Korean medicinal plants. Furthermore, the polyphenols isolated from these plants, procyanidin B-3, (+)-catechin, gallic acid, methyl gallate, quercetin, quercetin-3-O-[beta]-D-glucoside, quercetin-3-O-[beta]-galactoside, quercetin-3-O-rutinose and kaempferol, exerted strong DPPH radical-scavenging activity. These results suggest that the Korean medicinal plants and the polyphenois isolated from them that exhibited effective radical-scavenging activity may be promising agents for scavenging free radicals and treating diseases associated with excess free radicals.
Key words: 1,1-Diphenyl-2-picrylhydrazyl radical, Korean medicinal plant, polyphenol
Free radicals are now widely accepted as factors that contribute to the pathogenesis of a wide range of common and age-related degenerative diseases through the oxidative modification of DNA, proteins and vital molecules. Antioxidants, which protect against oxidative damage induced by free radicals, prevent the onset and progression of disease (Cutler, 1991; Meydani et al. 1998). Therefore, interest has been focused on the development of safe, effective and non-toxic antioxidants. Since ancient times, humans have derived many benefits from natural plants and compounds. It has generally been recognized that traditional Oriental medicines have unique therapeutic roles in the prevention and treatment of many human diseases related to excess free radicals. In addition, there is considerable evidence that polyphenols isolated from Oriental medicinal plants are potential therapeutic agents (Castillo et al. 1989; Inoue and Jackson, 1999; Middleton et al. 2000; Packer et al. 1999; Robak and Marcinkiewicz, 1995). Their beneficial roles are mainly attributable to antioxidative and radical-scavenging activities and many of these compounds have been shown experimentally and clinically to have antiradical and antioxidant properties (Dong et al. 1996; Yokozawa et al. 1996a, b, 1997a, b; Zhao et al. 1995). Koreans have also used and cultivated various traditional herbs with medicinal functions, but we could find hardly any scientific studies about the antiradical or antioxidant activities of Korean medicinal plants and compounds isolated from them.
A simple and rapid screening method is needed to search for promising agents from numerous plants. Therefore, in this study, we employed a stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-generating system, because it can be used to assay a large number of samples in a short time and is sensitive enough to detect natural and synthetic antioxidants at low concentrations. We used this system to carry out primary screening for antiradical activities among various Korean medicinal plants and their main compounds.
* Materials and Methods
Korean medicinal plants
The authorities for Korean medicinal plants used in this study were described in previous reports (Hur et al. 2001; Park and Ok, 1993; Park et al. 1993, 1996, 2000a, b, c; Young et al. 1987a, b). MeOH extracts of the following 11 kinds of Rosaceae and 12 other kinds of Korean medicinal plants were prepared: Rosa rugosa (root), Rosa davurica (root and leaf), Prunus persica (L.) Batsch (leaf), Prunus sargentii Rehder (leaf and stem), Rosa maximowicziana Regel (leaf and stem), Rosa acicularis Lindl. (leaf and stem), Rosa wichuraiana Crep. (leaf and stem), Rubus corchorifolius L. fil. (leaf), Rubus crataegifolius Bunge (stem), Sorbus alnifolia (S. et. Z.) K. Koch. (stem), Stephanandra incisa Zabel (stem), Eucommia ulmoides (leaf), Zanthoxylum piperitum (leaf, root, fructus and stem), Cudrania tricuspidata (leaf), Houttuynia cordata (aerial part), Angelica keiskei (aerial part), Cirsium japonicum var. ussuriense (aerial part), Ulmus parvifolia (leaf), Oenanthe javanica (aerial part), Armoracia rusticana (aerial part), Orostachysjaponicus (aerial part), Cedrela sinensis (rachis) and Nelumbo nucifera (leaf).
Isolation of compounds
The MeOH extracts were partitioned using organic solvents of different polarities to afford C[H.sub.2][Cl.sub.2], EtOAc, n-BuOH and [H.sub.2]O fractions, in sequence, as shown in Fig. 1. The EtOAc fraction of each plant was subjected to Silica gel chromatography with CH[Cl.sub.3]-MeOH-[H.sub.2]O (25:7: 5, lower layer; 7:3:1, lower layer; 65:35:10, lower layer) as eluent, to yield kaji-ichigoside [F.sub.1], procyanidine B-3, rosamultin, (+)-catechin, methyl gallate, gallic acid and quercetin-3-O-[beta]-D-galactoside from Rosa rugosa (Young et al. 1987a, b; Park and Ok, 1993); 3,4-dihydroxybenzoic acid, hesperidin, quercetin, quercetin-3-O-[beta]-D-galactoside, quercetin-3-O-[alpha]-L-rhainnoside and kaempferol-3-O-[alpha]-L-rhamnoside from Zanthoxylum piperitum (Hur et al. 2001); quercetin, quercetin-3-O-[beta]-D-galactoside, quercetin 3-O-[alpha]-L-rhamnoside and kaempferol-3-O-[alpha]-L-rhamnoside from Houttuynia cordata (Park et al. 2000a); kaempferol-3-O-[beta]-D-xyloside, kaempferol-3-O-[beta]-D-galactoside and kaempferol-3-O-[beta]-D-xylosyl (1 [right arrow] 2)-[beta]-D-galactoside from Armoracia rusticana (Park et al. 2000b); methyl gallate, gallic acid, 3,4-dihydroxyben-zoic acid, 4-hydroxybenzoic acid, kaempferol, kaempferol-3-O-[beta]-D-galactoside, kaempferol 3-O-[beta]-D-glucoside, quercetin and quercetin 3-O-[beta]-D-glucoside from Orostachys japonicus (Park et al. 2000c); and quercetin-3-O-[beta]-D-glucoside, quercetin 3-O-[alpha]-L-rhamnoside, quercetin 3-O-rutinoside, (+)-catechin, methyl gallate and adenosine from Cedrela sinensis (Park et al. 1993, 1996), as described previously.
[FIGURE 1 OMITTED]
Determination of DPPH radical levels
Aliquots (100-[micro]l each) of aqueous solutions of the samples (control: 100 [micro]l distilled water) were added to an EtOH solution of DPPH (60 [micro]M) in microwells, according to the method of Hatano et al. (1989). After being mixed gently and left for 30 min at room temperature, the DPPH radical level of each well was determined using a Microplate Reader (Model 3550-UV, Bio-Rad, Tokyo, Japan). The antioxidant activity of each sample was expressed in terms of the I[C.sub.50] value (concentration in [micro]g/ml or [micro]M required to inhibit DPPH radical formation by 50%) determined from the log dose-inhibition curve. L-Ascorbic acid and 2,6-di-t-butyl-4-methylphenol were used as positive controls.
DPPH radical-scavenging activities of MeOH extracts of Rosaceae and other Korean medicinal plants
Table 1 shows the DPPH radical-scavenging activities of MeOH extracts of Korean medicinal plants of the Rosaceae family. All the Rosaceae plants tested showed I[C.sub.50] values below 10 [micro]g/ml, except for Prunus sargentii Rehder and Rubus corchorifolius L. fil. The most potent DPPH radical scavenger was Rosa rugosa, which showed an I[C.sub.50] value of 1.23 [micro]g/ml. Rosa davurica, Rosa acicularis Lindl. and Rosa wichuraiana Crep. also showed strong scavenging effects, with I[C.sub.50] values below 3 [micro]g/ml. After these plants the order of potency was Sorbus alnifolia (S. et. Z.) K. Koch., Rosa maximowicziana Regel, Stephanandra incisa Zabel, Prunus persica (L.) Batsch and Rubus crataegifolius Bunge with I[C.sub.50] values of 4.14, 4.63 (leaf) and 4.42 (stem), 4.66, 5.17 and 9.09 [micro]g/ml, respectively.
Table 2 summarizes the DPPH radical-scavenging activities of MeOH extracts of several Korean medicihal plants besides the Rosaceae. Most of the extracts examined were effective DPPH radical scavengers, showing 50% inhibition at concentrations below 100 [micro]g/ml. Cedrela sinensis showed the strongest scavenging activity, with an I[C.sub.50] value of 1.66 [micro]g/ml. In addition, Nelumbo nucifera, Eucommia ulmoides and Zanthoxylum piperitum (leaf) were effective DPPH radical scavengers with I[C.sub.50] values of 3.36, 6.69 and 7.41 [micro]g/ml, respectively. Thereafter, the order of scavenging potency was Cudrania tricuspidata, Zanthoxylum piperitum, Houttuynia cordata, Angelica keiskei, Cirsium japonicum var. ussuriense, Ulmus parvifolia and Oenanthe javanica, whereas Armoracia rusticana and Orostachys japonicus showed relatively weak DPPH radical-scavenging activities with I[C.sub.50] values above 50 [micro]g/ml.
DPPH radical-scavenging activities of the compounds isolated from Korean medicinal plants
As shown in Table 3, of the polyphenols, procyanidin B-3, (+)-catechin, methyl gallate, gallic acid, quercetin, quercetin-3-O-[beta]-D-galactoside, quercetin-3-O-[beta]-D-glucoside and quercetin-3-O-rutinose exerted strong radical-scavenging activities. Procyanidin B-3, methyl gallate, gallic acid and (+)-catechin from Rosa rugosa showed I[C.sub.50] values of 1.47, 1.63, 1.65 and 2.93 [micro]M, respectively. Methyl gallate, gallic acid and (+)-catechin were also isolated from Orostachys japonicus or Cedrela sinensis. Quercetin, quercetin-3-O-[beta]-D-galactoside, quercetin-3-O-[beta]-D-glucoside and quercetin-3-O-rutinose were isolated from Zanthoxylum piperitum, Houttuynia cordata, Orostachys japonicus or Cedrela sinensis, and they exhibited high DPPH radical-scavenging activities with I[C.sub.50] values of 2.75, 2.50, 1.66 and 1.97 [micro]M, respectively. Kaempferol from Orostachys japonicus showed marked DPPH radical-scavenging activity with an I[C.sub.50] values of 6.54 [micro]M, whereas the derivatives of kaempferol from Armoracia rusticana, Zanthoxylum piperitum and Houttuynia cordata showed weak activities, with I[C.sub.50] values above 100 [micro]M.
The radical reactions that result in cellular and tissue damage are important in the occurrence of diseases and contribute to their pathology. Free radicals exert damaging effects on the cell components by oxidizing lipids of cell, lysosomal and microsomal membranes (Pederson and Aust, 1975; Tappel, 1973; Wills and Wilkinson, 1966). Proteins are damaged by cross-linking of amino acids and inactivation of some enzymes is also observed (Demopoulos, 1973). Furthermore, diseases caused by radicals are the result of an imbalance between the extent of the cellular damage induced by radical formation and the efficiency of defense mechanisms. They are now considered to contribute sigificantly to over 50 diseases, including inflammatory injury such as glomerulonephritis, vasculitis and rheumatoid arthritis, gastrointestinal diseases, cardiovascular disorders, nervous system disorders, and so on (Halliwell, 1987). Therefore, radical scavengers give promising indications of new therapeutic approaches. Marked free radical-scavenging activities of many traditional herb plants and their constituents have been demonstrated both in vivo and in vitro, and these activities are thought to contribute to their pharmacological effects (Hatano et al. 1989; Robak and Grylewski, 1996; Yokozawa et al. 1997a, b, 1998a, b; Zhao et al. 1995). Korean medicinal plants are also suspected to be potent free radical scavengers that can protect tissues and cells from injury caused by excess free radicals and may provide novel therapies for various pathological conditions. However, scientific research into the antioxidant activities of Korean medicinal plants is rarely carried out.
Up to now, several methods and procedures, both in vivo and in vitro, have been established for evaluating the antiradical and antioxidant activities of compounds (Bindoli et al. 1985; McCord and Fridovich, 1968; Nishikimi et al. 1972; Yokozawa et al. 1995). In this study, we used a simple and rapid method, a DPPH radical-generating system, in which extracts or components of medicinal plants scavenge free radicals directly. This DPPH system evidently offers a convenient and accurate method for titrating the oxidizable groups of natural and synthetic antioxidants. Most of the Korean medicinal plants tested in this system demonstrated radical-scavenging activity, indicating that they could be promising agents for scavenging free radicals and treating diseases related to free radical reactions.
Plants of the Rosaceae have been used as folk medicines to treat several disorders, such as diabetes mellitus, mastitis, asthma, dyspepsia, gastroenteritis and menoxenia that are at least partially attributable to free radical presence although scientific confirmation of their benefits has not yet been reported. Among the Rosaceae tested, Rosa rugosa and Rosa davurica showed high DPPH radical-scavenging activities (Table 1), indicating that they may be useful therapeutic agents for treating radical-related pathological damage through scavenging free radicals. The root of Rosa rugosa, a perennial shrub, has been used as an astringent and stomachic, and it is known as a Korean folk remedy for treating mastiffs and diabetes mellitus (Song et al. 1977). In fact, the hypoglycemic effects of Rosaceae plants in rats with alloxan- or streptozotocin-induced diabetes are well established (Lemus et al. 1999; Song et al. 1977). Furthermore, Rosa rugosa has been reported to show a hypolipidemic effect through the inhibition of microsomal HMG-CoA reductase activity, resulting in the suppression of cholesterol synthesis (Lee et al. 1991), and the juice of Rosa rugosa fruit strongly inhibited the proliferation of cancer cell lines and induced differentiation of HL-60 leukemia cells (Yoshizawa et al. 2000a, b). In addition, the results of our study suggest that Rosa davurica, which has been used as a traditional medicine for the treatment of various disorders, could be expected to exert therapeutic properties by virtue of its free radical-scavenging properties.
We also investigated the DPPH radical-scavenging activities of other families of Korean medicinal plants besides Rosaceae (Table 2). Of these, Cedrela sinensis, Nelumbo nucifera, Eucommia ulmoides, Zanthoxylum piperitum, Cudrania tricuspidata and Houttuynia cordata showed strong DPPH radical-scavenging activities. These plants have been used widely since ancient times to treat several pathological conditions. Nelumbo nucifera, which showed an I[C.sub.50] value of 3.36 [micro]g/ml, is in wide use in folk medicine as a tonic, hemostatic and febrifuge, and also for to treating enuresis, gynecological disorders and enterorrhagia. Eucommia ulmoides is known as a tonic, abirritant and analgesic, and is used traditionally as a therapeutic agent for lumbago and arthritis, although the scientific evidence of its pharmacological activity has not yet been supported. Zanthoxylum piperitum, employed in traditional Asian medicine (Shibata et al. 1999), is used as a spice in Asian cuisine (Bryant and Meizine, 1999; Epple et al. 2001). It is also well known as an antidote, an antiphlogistic and a cure for gastrointestinal disorders. Moreover, Zanthoxyli Fructus, the pericarp of Zanthoxylum piperitum, has been recognized to act on the gastrointestinal tract, and so has been used as an aid to digestion since ancient times. It is also a crude drug component of Dai-kenchuto, a Chinese prescription used frequently to treat paralytic ileus after laparotomy and severe constipation (Hashimoto et al. 2001). In addition, Houttuynia cordata Thunb. is described as a pungent tasting herb with good properties and is used for treating hypertension and edema, and as a detoxicant, diuretic, antiinflammatory, antipyretic, antipumlent and diuretic agent (Probstle and Bauer, 1992). Furthermore, Hayashi et al. (1995) reported that it showed direct inhibitory activity against herpes simplex virus type I, influenza virus and human immunodeficiency virus type 1 (HIV-1) without showing cytotoxicity to the host. In particular, quercetin, a flavonoid present in Houttuynia cordata, has been reported to show inhibitory effects on several viruses (Mucsi and Pragai, 1985). Although Orostachys japonicus showed relatively weak radical-scavenging activity (I[C.sub.50] value > 50 [micro]g/ml), it contains high levels of tannins and flavonoids, suggesting that the compounds isolated from this plant would be potential radical scavengers. Traditionally, it has been used as an antiinflammatory agent to treat hepatitis, boils and piles, and as a hemostatic agent for the treatment of hematemesis, epistaxis and hemafecia. In addition, Yoon et al. (2000) reported that Orostachys japonicus A. Berger had a neuroprotective effect against [H.sub.2][O.sub.2]-induced apoptosis in a hypothalamic neuronal cell line, indicating that this plant has a potential use in the prevention and treatment of neurodegenerative disease. Although several beneficial effects of the Korean medicinal plants described above have long been known, protective activities of these plants against oxidative damage that would ameliorate various common and age-related degenerative diseases have not yet been demonstrated. Therefore, the results of our present study serve as a good indication of Korean medicinal plants that have free radical-scavenging activity.
Medicinal plants consist of many kinds of components and their biological activities are not usually attributable to a single moiety. Although it remains unclear which of the components of Korean medicinal plants are the active compounds, polyphenols have received increasing attention recently because of some interesting new findings regarding their biological activities. We therefore focused on the free radical-scavenging activities of polyphenols isolated from Korean medicinal plants (Table 3). Zanthoxylum piperitum, Houttuynia cordata, Armoracia rusticana and Orostachys japonicus showed relatively low activity compared with Rosa rugosa. They also, however, contain the polyphenols that are known as the active components of Rosa rugosa, therefore, we also isolated polyphenols from them to compare their activity with that of the compounds from Rosa rugosa. Our present study indicates that procyanidin B-3, gallic acid, methyl gallate and (+)-catechin isolated from Rosa rugosa, Orostachys japonicus and Cedrela sinensis are potential free radical scavengers. Radicals that react with polyphenols are known generally to be highly reactive species, which undergo a variety of reactions with polyphenols to give dimers through C-C and C-O coupling, thus halting the free radical chain reactions. The strong radical-scavenging activity of polyphenol may be due to formation of stable radicals. Several reports support the concept that polyphenols scavenge reactive free radicals, such as reactive oxygen species and the DPPH radical (Hatano et al. 1989; Yokozawa et al. 1998a, b; Yoshida et al. 1989). In particular, the galloyl radical, which is formed during the reaction of tannins with DPPH, is a highly reactive species that can participate easily in a variety of reactions to yield dimers through C-C and C-O coupling, thus inhibiting the free radical reaction (Yoshida et al. 1989). Hong et al. (1995) also reported that they have been shown to protect lipids from peroxidation.
Flavonoids have attracted a great deal of attention in relation to their potential for beneficial effects on health. Antioxidant activities account at least partly for these effects, because oxidative stress leads to a variety of pathophysiological events. Over the past few years, several experimental studies have demonstrated biological and pharmacological properties of many flavonoids, especially their antiinflammatory (Middleton et al. 2000), antioxidant (Packer et al. 1999; Robak and Marcinkiewicz, 1995) and antitumor (Castillo et al. 1989; Inoue and Jackson, 1999) effects, which are associated with free radical-scavenging actions. In our present investigation, the flavonoids, quercetin, quercetin-3-O-[beta]-glucoside, quercetin-3-O-[beta]-galactoside, quercetin-3-O-rutinose and kaempferol, showed strong DPPH radical-scavenging activities. In particular, quercetin, which has a 3',4'-dihydroxyl group, exhibited high radical-scavenging activity. Heilmann et al. (1995) reported that all flavonoid compounds possessing this active 3',4'-dihydroxyl substituent, showed excellent inhibitory activity against the DPPH radical. In addition, the radical-scavenging activities of flavonoids may be influenced greatly by gtycosylation. Although quercetin-3-O-[beta]-D-glucoside, quercetin-3-O-[beta]-galactose and quercetin-3-O-rutinose showed strong DPPH radical-scavenging activities similar to or greater than that of quercetin, quercetin-3-O-[alpha]-L-rhamnoside showed relatively low activity. Interestingly, kaempferol showed a strong inhibitory action against the DPPH radical, whereas glycosylated kaempferols showed weak activity. Kaempferol has four non-ortho-hydroxyl groups in its structure, suggesting that radical-scavenging activity may be enhanced by increasing hydroxyl substitution and that these four hydroxyl groups could confer strong antioxidant activity. We could hypothesize that glycosylation may reduce the number of free hydroxyl groups or destroy the ortho-hydroxyl structure, and the sugar linkage may hinder access of free radical scavengers to the center of the DPPH radical. A study on the relationship between glycosylation of kaempferol and radical-scavenging activity is in progress.
The strengths of the radical-scavenging effects of polyphenols are also related to the nature of the radical species, such as DPPH or peroxy radicals. The present study is only a preliminary one, as the results obtained may not represent all the mechanisms and activities of Korean medicinal plants and compounds derived from them against radicals and peroxidation. Therefore, in view of the results of the present investigation, further studies should be conducted.
Table 1. DPPH radical scavenging activity of MeOH extracts for Korean medicinal plants (Rosaceae). Scientific name Used part I[C.sub.50] value ([micro]g/ml) Rosa rugosa root 1.23 Rosa davurica root 1.67 leaf 2.47 Prunus persica (L.) Batsch leaf 5.17 Prunus sargentii Rehder leaf 49.40 stem 3.21 Rosa maximowicziana Regel leaf 4.63 stem 4.42 Rosa acicularis Lindl. leaf 2.70 stem 2.80 Rosa wichuraiana Crep. leaf 2.98 stem 2.80 Rubus corchorifolius L. fil. leaf 14.01 Rubus crataegifolius Bunge stem 9.09 Sorbus alnifolia (S. et. Z.) K. Koch. stem 4.14 Stephanandra incisa Zabel stem 4.66 Table 2. DPPH radical scavenging activity of MeOH extracts for Korean medicinal plants. Scientific name Used part I[C.sub.50] value ([micro]g/ml) Eucommia ulmoides leaf 6.69 Zanthoxylum piperitum leaf 7.41 Cudrania tricuspidata leaf 13.29 Zanthoxylum piperitum root 15.29 Zanthoxylum piperitum fructus 15.66 Zanthoxylum piperitum stem 22.04 Houttuynia cordata aerial part 22.74 Angelica keiskei aerial part 23.34 Cirsium japonicum var. ussuriense aerial part 24.40 Ulmus parvifolia leaf 26.23 Oenanthe javanica aerial part 35.52 Armoracia rusticana aerial part 51.15 Orostachys japonicus aerial part 78.92 Cedrela sinensis rachis 1.66 Nelumbo nucifera leaf 3.36 Table 3. DPPH radical scavenging activity on compounds isolated from Korean medicinal plants. Material I[C.sub.50] I[C.sub.50] value value ([micro]g/ml) ([micro]g/ml) Rosa rugosa MeOH extract 1.23 Root Kaji-ichigoside [F.sub.1] > 100 > 100 Procyanidin B-3 0.85 1.47 Rosamultin 6.50 10.00 (+)-Catechin 0.85 2.93 Methyl gallate 0.30 1.63 Stem Methyl gallate 0.30 1.63 Gallic acid 0.28 1.65 Quercetin-3-O-[beta]-D-galactoside 1.16 2.50 Zanthoxylum piperitum MeOH 7.41 extract (leaf) 3,4-Dihydroxybenzoic acid 1.73 11.23 Hesperidin 71.15 > 100 Quercetin 0.83 2.75 Quercetin-3-O-[beta]-D-galactoside 1.16 2.50 Quercetin-3-O-[alpha]-L-rhamnoside 9.07 20.25 Kaempferol-3-O-[alpha]-L-rhamnoside 49.63 > 100 Houttuynia cordata MeOH extract 22.74 (aerial part) Quercetin 0.83 2.75 Quercetin-3-O-[beta]-D-galactoside 1.16 2.50 Quercetin-3-O-[alpha]-L-rhamnoside 9.07 20.25 Kaempferol-3-O-[alpha]-L-rhamnoside 49.63 > 100 Armoracia rusticana MeOH extract 51.15 (aerial part) Kaempferol-3-O-[beta]-D-xyloside 63.36 > 100 Kaempferol-3-O-[beta]-D-galactoside > 100 > 100 Kaempferol-3-O-[beta]-D-xylosyl > 100 > 100 (1 [right arrow] 2)-[beta]-D- galactoside Orostachys japonicus MeOH extract 78.92 (aerial part) Methyl gallate 0.30 1.63 Gallic acid 0.28 1.65 3,4-Dihydroxybenzoic acid 1.73 11.23 4-Hydroxybenzoic acid > 100 > 100 Kaempferol 1.87 6.54 Kaempferol-3-O-[beta]-D-galactoside > 100 > 100 Kaempferol-3-O-[beta]-D-glucoside 22.67 50.60 Quercetin 0.83 2.75 Quercetin-3-O-[beta]-D-glucoside 0.77 1.66 Cedrela sinensis MeOH extract (rachis) 1.66 Quercetin-3-O-[beta]-D-glucoside 0.77 1.66 Quercetin-3-O-[alpha]-L-rhamnoside 9.07 20.25 Quercetin-3-O-rutinose 1.20 1.97 (+)-Catechin 0.85 2.93 Methyl gallate 0.30 1.63 Adenosine > 100 > 100 L-Ascorbic acid 0.95 5.39 2,6-Di-t-butyl-4-methylphenol 77.18 > 100
Bindoli A, Valente M, Cavallini L (1985) Inhibitory action of quercetin on xanthine oxidase and xanthine dehydrogenase activity. Pharm Res Commun 17: 831-839
Bryant BE Mezine I (1999) Alkylamides that produce tingling paresthesia activate tactile and thermal trigeminal neurons. Brain Res 842: 452-460
Castillo MH, Perkins E, Campbell JH, Doerr R, Hassett JM, Kandaswami C, Middleton E Jr (1989) The effects of the bioflavonoid quercetin on squamous cell carcinoma of head and neck origin. Am J Surg 158: 351-355
Cutler RG (1991) Antioxidants and aging. Am J Clin Nutr 53: 373S-379S
Demopoulos HB (1973) The basis of free radical pathology. Fed Proc 32: 1859-1861
Dong E, Yokozawa T, Kashiwagi H, Hattori M, Watanabe H, Oura H (1996) The role of total ginseng saponin and its components in antiperoxidation in vitro. Nat Med 50: 128-134
Epple G, Bryant BP, Mezine I, Lewis S (2001) Zanthoxylum piperitum, an asian spice, inhibits food intake in rats. J Chem Ecol 27: 1627-1640
Halliwell B (1987) Oxidants and human disease: some new concepts. FASEB J 1: 358-364
Hashimoto K, Satoh K, Kase Y, Ishige A, Kubo M, Sasaki H, Nishikawa S, Kurosawa S, Yakabi K, Nakamura T (2001) Modulatory effect of aliphatic acid amides from Zanthoxylum piperitum on isolated gastrointestinal tract. Planta Med 67: 179-181
Hatano T, Edamatsu R, Hiramatsu M, Mori A, Fujita Y, Yasuhara T, Yoshida T, Okuda T (1989) Effects of the interaction of tannins with co-existing substances. VI. Effects of tannins and related polyphenols and superoxide anion radical, and on 1,1-diphenyl-2-picrylhydrazyl radical. Chem Pharm Bull 37: 2016-2021
Hayashi K, Kamiya M, Hayashi T (1995) Virucidal effects of the steam distillate from Houttuynia cordata and its components on HSV-1, influenza virus, and HIV. Planta Med 61: 237-241
Heilmann J, Merfort I, Weiss M (1995) Radical scavenger activity of different 3',4'-dihyroxyflavonols and 1,5-dicafeoylquinic acid studied by inhibition of chemiluminescence. Planta Med 61: 435-438
Hong CY, Wang CP, Huang SS, Hsu FL (1995) The inhibitory effect of tannins on lipid peroxidation of rat heart mitochondria. J Pharm Pharmacol 47: 138-142
Hur JM, Park JC, Hwang YH (2001) Aromatic acid and flavonoids from the leaves of Zanthoxylum piperitum. Nat Prod Sci 7: 23-26
Inoue T, Jackson EK (1999) Strong antiproliferative effects of baicalein in cultured rat hepatic stellate cells. Eur J Pharmacol 378: 129-135
Lee SY, Kim JD, Lee YH, Rbee HI, Choi YS (1991) Influence of extract of Rosa rugosa roots on lipid levels in serum and liver of rats. Life Sci 49: 947-951
Lemus I, Garcia R, Delvillar E, Knop G (1999) Hypoglycaemic activity of four plants used in Chilean popular medicine. Phytother Res 13: 91-94
McCord JM, Fridovich I (1968) The reduction of cytochrome c by milk xanthine oxidase. J Biol Chem 243: 5753-5760
Meydani M, Lipman RD, Han SN, Wu D, Beharka A, Martin KR, Bronson R, Cao G, Smith D, Meydani SN (1998) The effect of long-term dietary supplementation with antioxidants. Ann NY Acad Sci 854: 352-360
Middleton E Jr, Kandaswami C, Theoharides TC (2000) The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52: 673-751
Mucsi I, Pragai BM (1985) Inhibition of virus multiplication and alteration of cyclic AMP level in cell cultures by flavonoids. Experientia 41: 930-931
Nishikimi M, Rao NA, Yaki K (1972) The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 46: 849-854
Packer L, Rimbach G, Virgili F (1999) Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Rad Biol Med 27: 704-724
Park JC, Ok KD (1993) Phenolic compounds isolated from Rosa rugosa in Korea. Yakhak Hoeji 37: 365-369
Park JC, Young HS, Yu YB, Lee JH (1993) Studies on the chemical components and biological activities of edible plants in Korea (1). Phenolic compounds from the leaves of Cedrela sinensis A. Juss. Yakhak Hoeji 37: 306-310
Park JC, Choi JS, Ok KD, Yu YB, Lee JH (1996) Phenolic compounds from the rachis of Cedrela sinensis. Kor J Pharmacog 27: 219-223
Park JC, Hur JM, Park JG, Lee JH, Sung N J, Choi MR, Song SH, Kim MS, Choi JW (2000a) The effects of Houttuynia cordata on the hepatic bromobenzene metabolizing enzyme system in rats and isolation of phenolic compounds. Kor J Pharmacog 31: 228-234
Park JC, Choi JS, Yu YB, Lee JH (2000b) Effect of methanol extract and kaempferol glycosides from Armoracia rusticana on the formation of lipid peroxide in bromobenzene-treated rats in vitro. Kor J Pharmacog 31: 228-234
Park JG, Park JC, Hur JM, Park SJ, Choi DR, Sin DY, Park KY, Cho HW, Kim MS (2000c) Phenolic compounds from Orostachys japonicus having anti-HIV-1 protease activity. Nat Prod Sci 6: 117-121
Pederson TC, Aust SD (1975) The mechanism of liver microsomal lipid peroxidation. Biochim Biophys Acta 385: 232-241
Probstle A, Bauer R (1992) Aristolactams and a 4,5-dioxoaporphine derivative from Houttuynia cordata. Planta Med 58: 568-569
Robak J, Gryglewski RJ (1996) Bioactivity of flavonoids. Pol J Pharmacol 48: 555-564
Robak J, Marcinkiewicz E (1995) Scavenging of reactive oxygen species as the mechanism of drug action. Pol J Pharmacol 47: 89-98
Shibata C, Sasaki I, Naito H, Ueno T, Matsuno S (1999) The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs. Surgery 126: 918-924
Song SO, Kim KH, Kang DH (1977) Effect of tap Japanese rose root-extract on the blood level in rat. Yonsei J Med Sci 10: 125-128
Tappel AL (1973) Lipid peroxidation damage to cell components. Fed Proc 32: 1870-1874
Wills ED, Wilkinson AE (1966) Release of enzymes from lysosomes by irradiation and the relation of lipid peroxide formation to enzyme release. Biochem J 99: 657-566
Yokozawa T, Fujitsuka N, Oura H, Moil A, Kashiwagi H (1995) Determination of radical species in the kidney of rats with chronic renal failure by the spin trapping method. Nephron 70: 382-384
Yokozawa T, Dong E, Watanabe H, Oura H (1996a) Increase of active oxygen in rats after nephrectomy is suppressed by ginseng saponin. Phytother Res 10: 569-572
Yokozawa T, Dong E, Liu ZW, Oura H, Nishioka I (1996b) Antiperoxidation activity of Wen-Pi-Tang in vitro. Nat Med 50: 243-246
Yokozawa T, Dong E, Liu ZW, Oura H (1997a) Antiperoxidation activity of traditional Chinese prescriptions and their main crude drugs in vitro. Nat Med 51: 92-97
Yokozawa T, Dong E, Liu ZW, Shimizu M (1997b) Antioxidative activity of flavones and flavonols in vitro. Phytother Res 11: 446-449
Yokozawa T, Chen CP, Liu ZW (1998a) Effect of traditional Chinese prescriptions and their main crude drugs on 1,1-diphenyl-2-picrylhydrazyl radical. Phytother Res 12: 94-97
Yokozawa T, Chen CP, Dong E, Tanaka T, Nonaka G, Nishioka I (1998b) Study on the inhibitory effect of tannins and flavonoids against the 1,1-diphenyl-2-picrylhydrazyl radical. Biochem Pharmacol 56: 213-222
Yoon Y, Kim KS, Hong SG, Kang BJ, Lee MY, Cho DW (2000) Protective effects of Orostachysjaponicus A. Berger (Crassulaceae) on [H.sub.2][O.sub.2]-induced apoptosis in GT1-1 mouse hypothalamic neuronal cell line. J Ethnopharmacol 69: 73-78
Yoshida T, Mori K, Hatano T, Okumura T, Uehara I, Komagoe K, Fujita Y, Okuda T (1989) Studies on inhibition mechanism of autooxidation by tannins and flavonoids. V. Radical-scavenging effects of tannins and related polyphenols on 1,1-diphenyl-2-picrylhydrazyl radical. Chem Pharm Bull 37: 1919-1921
Yoshizawa Y, Kawaii S, Mimako U, Fukase T, Sato T, Murofushi N, Nishimura H (2000a) Differentiation-inducing effects of small fruit juices on HL-60 leukemia cells. J Agric Food Chem 48: 3177-3182
Yoshizawa Y, Kawaii S, Mimako U, Fukase T, Sato T, Tanaka R, Murofushi N, Nishimura H (2000b) Antiproliferative effects of small fruit juices on several cancer cell lines. Anticancer Res 20: 4285-4290
Young HS, Park JC, Choi JS (1987a) Isolation of (+)-catechin from the roots of Rosa rugosa. Kor J Pharmacog 18: 177-179
Young HS, Park JC, Choi JS (1987b) Triterpenoid glycosides from Rosa rugosa. Arch Pharm Res 10: 219-222
Zhao Y, Wang X, Kawai M, Liu J, Liu M, Mori A (1995) Antioxidant activity of Chinese ant extract preparations. Acta Med Okayama 49: 275-279
T. Yokozawa, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
Tel.: ++81-76-434-7631; Fax: ++81-76-434-4656
E. J. Cho (1), T. Yokozawa (1), D. Y. Rhyu (1), S. C. Kim (2), N. Shibahara (1), and J. C. Park (2)
(1) Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
(2) Department of Oriental Medicine Resources, Sunchon National University, Sunchon, Korea
|Printer friendly Cite/link Email Feedback|
|Author:||Cho, E.J.; Yokozawa, T.; Rhyu, D.Y.; Kim, S.C.; Shibahara, N.; Park, J.C.|
|Publication:||Phytomedicine: International Journal of Phytotherapy & Phytopharmacology|
|Date:||Jul 1, 2003|
|Previous Article:||Inhibitory activity of xanthine oxidase and superoxide-scavenging activity in some taxa of the lichen family Graphidaceae.|
|Next Article:||Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm.|