A Review of Malaysian Medicinal Plants with Potential Anti-Inflammatory Activity.
A primary physiologic defence mechanism known as inflammation helps to protect the body from noxious stimuli, resulting in the swelling or edema of tissues, pain, or even cell damage. The main purpose of this mechanism is to repair and return the damaged tissue to the healthy state . The increase in size of the vessels only occurs around the inflammatory loci (i.e., neutrophils, macrophages, and lymphocytes) during the early stages of inflammation, but after 24 hours, many kinds of cells reach neutrophils, followed by macrophages within 48 hours and lymphocytes after several days . It is well known that the disruption of cells occurs during inflammation processes, leading to the release of arachidonic acid, and further undergoes two metabolic pathways known as the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. COX pathways consist of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), while 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX), and 15-lipoxygenase (15-LOX) are the examples of the LOX pathway. The products of the COX pathway are prostaglandins (mediators of acute inflammation) and thromboxanes, while those of the LOX pathway are leukotrienes and hydroperoxy fatty acids [2, 3].
Clinically, the common signs of inflammation include pain, heat, redness, loss of function, and swelling on the affected tissue . Other signs include fever, leukocytosis, and sepsis. There are many causes of inflammation such as pathogens (e.g., bacteria, viruses, and fungi), external injuries, and effects of chemicals or radiation. Inflammation can be classified into two categories: acute and chronic inflammation. Acute inflammation is considered as the first line of defence against injury. It occurs in a short period of time and is manifested by the excretion of fluid and plasma proteins along with the emigration of leukocytes such as neutrophils. Meanwhile, chronic inflammation takes prolonged duration and is manifested by the action of lymphocytes and macrophages, resulting in fibrosis and tissue necrosis. Inflammation is considered as one of the most common concern of diseases, ranging from the minor to a serious condition like cancer. Based on the recent advancement in imaging technologies, the chronic vascular inflammation is not involved in atherosclerosis but also in arterial hypertension and metabolic syndrome .
Currently, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, aspirin, diclofenac, and celecoxib are extensively used for the treatment of inflammation. These drugs exhibit their anti-inflammatory properties by inhibiting the COX-1 activity and thus preventing the synthesis of prostaglandins . However, the major concern is that NSAIDs may cause various side effects such as gastrointestinal complications . Considering this, the quests for the new drug with anti-inflammatory properties from the medicinal plants with free of or fewer side effects are greatly needed for the pharmaceutical industry [7, 8].
Plant-based or herbal medicine has been used traditionally to treat pain, inflammation, and inflammatory-mediated pain . Malaysia is among the world's 12 megadiverse countries where endemism is highest. At least a quarter of our tree flora is not found elsewhere in the world, and many of our herbaceous flora and other groups of species are unique . In Malaysia, about 2000 medicinal plant species are reported to possess health benefit properties . Based on nutritional studies, these medicinal plants contain diverse nutritive values and possess potential bioactive compounds with the activity related to the various inflammation disorders including gout  or age-related diseases . Hence, this current review aims to disseminate detailed information on the anti-inflammatory potential of Malaysian medicinal plants, focusing on the bioactive phytochemicals, and mechanisms of action against inflammation in both in vitro and in vivo studies.
The bibliographic research was performed in the following databases: PubMed, Google Scholar, Scopus, and ScienceDirect, where these databases were searched for relevant studies which included at least one keyword from each of the following: (i) inflammation, (ii) Malaysia, (iii) medicinal plants, (iv) mechanisms, (v) in vitro, and (vi) in vivo. No limit was placed on the search time frame in order to retrieve all relevant papers, and the last search was performed on April 20, 2018. About 96 papers have been reviewed including journal articles and proceedings as well as the reference lists of articles for additional relevant studies.
The World Health Organization (WHO) defines medicinal plants as plants which possess compounds that can be used for the therapeutic purposes as well as producing useful drugs from the metabolites. According to the WHO, medicinal plants are still being used by the people in developing countries to treat various diseases, and these products' market continue to grow  which gives a good sign of economic importance of medicinal plants. Based on the previous report, 15% out of 300,000 plant species in the world have been studied for the pharmacological activity. Interestingly, about 25% of modern medicines have been developed from the natural resources such as medicinal plants . Recently, the research on the medicinal plants for the health benefit purposes has increased worldwide and gained attention from all researchers all over the world including Malaysia. Malaysia is known as a country that is rich in the medicinal plant species. For instance, 1300 medicinal plant species and 7411 plant species have been recorded in Peninsular Malaysia and Sabah, respectively [16, 17].
Inflammation is a response of tissue to cell injury due to pathogens, damaged tissues, or irritants which initiates the chemical signals to heal the afflicted tissue . The leukocytes such as neutrophils, monocytes, and eosinophils are activated and migrated to the sites of damage. During the inflammatory processes, the excessive nitric oxide (NO) and prostaglandin [E.sub.2] ([PGE.sub.2]) as well as proinflammatory cytokines (i.e., tumour necrosis factor-alpha (TNF-[alpha]) and interleukins) are secreted by the activated macrophages. The nitric oxide and prostaglandin productions from the inducible nitric oxide synthase (iNOS) and COX-2, respectively, are the proinflammatory mediators responsible for many inflammatory diseases [19, 20]. Inflammation can be classified into two types known as acute and chronic inflammation. The vascular response to inflammation in the early stage (acute inflammation) can be clearly seen at the affected tissue as it becomes reddened due to the increase of blood flow and swollen due to edema fluid. Three main processes that involve during the vascular response to acute inflammation are (1) changes in vessel caliber and blood flow, (2) the increase in vascular permeability, and (3) fluid exudate formation. It is important to understand that an uncontrolled inflammation may contribute to many chronic illnesses . For instance, chronic inflammation may lead to infectious diseases and cancer , while the prolonged inflammation may cause abnormal gene expression, genomic instability, and neoplasia [23, 24]. Currently, NSAIDs exhibit great effects in inhibiting the activity of COX-1 and COX-2, but COX-1 inhibitors are reported to exert side effects such as gastrointestinal erosions and renal and hepatic insufficiency . COX-2 (Vioxx) also has been reported to cause serious cardiovascular events . To overcome this, many studies on anti-inflammatory drugs from natural resources have been conducted. Enzyme inhibitory assays (i.e., COX and LOX) have been extensively used to study the effectiveness of medicinal plants in treating the inflammation due to the presence of many phytochemicals, and they are being consumed as a food or food supplement for many years. The Malaysian medicinal plants that possess an anti-inflammatory activity are shown in Tables 1 and 2 for in vitro and in vivo studies, respectively. Based on the results obtained, many studies used the NO inhibition assay as a method to show the anti-inflammatory activity of the plants. Many diseases such as rheumatoid arthritis, diabetes, and hypertension have been reported to be occurred due to the excessive production of NO . NO is synthesized by inducible NO synthase which has three isomers: (i) neuronal nitric oxide synthase (nNOS), (ii) endothelial nitric oxide synthase (eNOS), and (iii) iNOS . For instance, signaling molecules such as mitogen-activated protein kinases (MAPKs), nuclear factor-kappa B (NF-[kappa]B), activator protein-1 (AP-1), and signal transducer and activator of transcription (STAT) regulate the inducible enzyme (i.e., iNOS), which then make this enzyme to be expressed in some tissues . Apart from the nitric oxide inhibition assay, some studies used the LOX assay in order to evaluate the anti-inflammatory of the plants. In this mechanism, arachidonic acid is metabolized by 5-LOX to various forms of inflammatory leukotrienes such as leukotriene (LT) [A.sub.4], [LTB.sub.4], [LTC.sub.4], [LTD.sub.4], and [LTE.sub.4] , where LTB4 (one of the mediators of inflammation) is reported to be the most crucial in the inflammatory response . To support this, it is reported that patients with rheumatoid arthritis and inflammatory bowel disease possess high levels of LTB4 [82, 83]. In addition, LTs are reported to be linked with few diseases such as bronchial asthma and skin inflammatory disorders . In 2011, Kwon et al.  demonstrated that esculetin, one of the examples of coumarins, exhibited anti-inflammatory activity in vivo against animal models of skin inflammation. In the LOX assay, any LOX inhibitors will reduce [Fe.sup.3+] to [Fe.sup.2+], providing a rapid colorimetric assay . Another common assay in determining the anti-inflammatory activity is COX. Two isoforms of COX, COX-1 (mainly involved in physiological functions and constitutively expressed) and COX-2 (involved in inflammation and induced in the inflamed tissue), are the enzymes responsible for the synthesis of prostaglandins . Besides, the COX-2 gene is also a gene for iNOS induced during inflammation and cell growth . The Griess assay is another assay commonly used in the murine macrophage cell line (RAW 264.7) as a culture medium in the cell-based study in order to determine the concentration of nitrite (NO2-), the stable metabolite of NO.
Based on Table 1 (in vitro study), 46 plants have been identified and studied for the anti-inflammatory activity from the previous studies. As a result, only two plants have been reported to exhibit more than 90% of antiinflammatory activity using the nitric oxide inhibition assay, which were Melicope ptelefolia (Tenggek burung) and Portulaca oleracea (Gelang pasir) with the values of 95.00% and 94.80% at 250 [micro]g/ml, respectively . Besides that, many previous studies had reported the plants which exerted anti-inflammatory activity between 70% and 80% at 100 [micro]g/ml to 2000 [micro]g/ml which can be considered to be higher such as Jatropha curcas (Jarak pagar), Curcuma longa (Kunyit), Boswellia serrata (Kemenyan), Labisia pumila (Kacip fatimah), Oenanthe javanica (Selom), Caricapapaya (Betik), and Eurycoma longifolia (Tongkat ali) with the values of 86.00%, 82.50%, 80.00%, 75.68%, 75.64%, 72.63%, and 70.97%, respectively [29, 31, 35, 36, 40, 42]. The moderate result of anti-inflammatory activity (50%-60%) also had been showed by several plants such as Phaleria macrocarpa (69.50%), Sauropus androgynus (68.28%), Piper sarmentosum (62.82%), Thymus vulgaris (62.00%), Barringtonia racemosa (57.70%), and Kaempferia galanga (57.82%) at 100 [micro]g/ml to 2000 [micro]g/ml [27, 31, 41, 43, 48]. In addition, plants from the Zingiberaceae, Lamiaceae, Annonaceae, and Fabaceae families have been studied extensively for the anti-inflammatory activity. Among these families, the active compound of Curcuma longa from the Zingiberaceae family, monodemethoxycurcumin, had the highest activity with 82.50% at 125 [micro]g/ml . Of the other study, Kaempferia galanga from the Zingiberaceae family exhibited moderate activity with 57.82% at 200 [micro]g/ml where the isolated compound, ethyl-pmethoxycinnamate, was found to have anti-inflammatory activity via inhibiting the actions of COX-1 and COX-2 . In the Lamiaceae family, Thymus vulgaris showed the highest percentage of anti-inflammatory activity compared to other plants with 62% at 100 [micro]g/ml , with the total phenolic content of 350 [micro]g GAE/ml.
In this study, it was found that the results of antiinflammatory activity of the methanolic extract of the leaves of Melicope ptelefolia (Tenggek burung) varied between two previous studies due to the different types of assays used by both studies: nitric oxide inhibition and soybean 15-lipoxygenase inhibition assays with the values of 95% and 72.3%, respectively [13, 45]. Another study also reported that the antiinflammatory activity of the methanolic extract of Litsea garciae fruits showed 9.42% (lipoxygenase assay) and 27.70% (hyaluronidase assay) . Based on these results, it can be concluded that different assays used might produce different results. For the COX inhibition assay, all the curcumins isolated from Curcuma longa rhizomes (i.e., curcumin I, curcumin II (monodemethoxycurcumin), and curcumin III (bisdemethoxycurcumin)) displayed greater inhibition of COX-2 compared to COX-1 at the same test concentration . For the Griess assay, all the species tested such as the leaves of Carica papaya, Sauropus androgynus, and Piper sarmentosum, the flowering stalk of Musa acuminata, and the whole plant of Oenanthe javanica displayed significant NO inhibitory activity in a concentration-dependent manner against IFN-[gamma]/LPS-treated macrophages .
For the in vivo study (Table 2), 30 plants have been identified in this study for the anti-inflammatory activity. Many of the studies from the previous years used the carrageenan-induced rat paw edema method (a reliable inflammation model) as this carrageenan has been found to be more trenchant in producing the edema compared to formalin . It is also one of the conventional methods used to evaluate the anti-inflammatory effect of drugs or medicinal plants at the acute stage  and involves a biphasic event. Normally, the release of histamine and serotonin happens in the early phase (1-2 h), while the second phase (3-5 h) involves the release of prostaglandins and kinins [90, 91]. For the edema formation, the rat paw is injected with carrageenan. This method is also a COX-dependent reaction with the control of arachidonate COX . The ability of the plant extracts to lessen the thickness of the rats' paw edema indicates the ability of these plant extracts to exert the anti-inflammatory properties. Based on Table 2, the highest dose of the extract used was 1000 mg/kg of body weight, while the lowest one was 3 mg/kg of body weight. Most of the previous studies reported that the extract was able to inhibit paw edema induced by carrageenan. For instance, a significant highest paw edema inhibition (93.34%) was observed in rats at a dose of 300 mg/kg of the Ardisia crispa (Mata pelandok) root extract . Another study also showed that a significant highest inhibition was observed in two isolated compounds from Sandoricum koetjape stems, 3-oxo-12-oleanen-29-oic acid and katonic acid with 94% and 81%, respectively, where 3-oxo-olean-12en-29-oic acid had the percentage inhibition almost similar to the reference drug, indomethacin (97%) .
Based on the results obtained, few studies isolated the bioactive compounds to be further analyzed for the antiinflammatory activity such as flavonoids (boesenbergin A, eupatorin, and sinensetin), coumarins (scopoletin and scoparone), triterpenoids (dammara-20,24-dien-3-one and 24-hydroxydammara-20,25-dien-3-one), steroids (cucurbitacin E), curcuminoids (monodemethoxycurcumin and bisdemethoxycurcumin), benzophenones (garsubellin A and garcinielliptin oxide), cinnamic acid (ethyl-p-methoxycinnamate), alkaloids (kokusaginine), benzene (p-O-geranylcoumaric acid), 4-[(20-O-acetyl-[alpha]-L-rhamnosyloxy)benzyl]isothiocyanate, 4-[(30-O-acetyl-[alpha]-L-rhamnosyloxy)benzyl]isothiocyanate, and 4-[(40-O-acetyl-[alpha]-L-rhamnosyloxy)benzyl]isothiocyanate [28, 30, 32, 33, 35, 38, 41, 45-47]. Interestingly, some of them exerted significant inhibition on inflammation. In 2000, Abad et al.  evaluated the common anti-inflammatory drug naproxene isolated from Musa acuminate (pisang abu nipah) which exhibited good inhibition in COX-1 and COX-2 activities. Besides, in Carica papaya leaves, coumarin was isolated and exerted anti-inflammatory activity by suppressing the cytokine TNF-[alpha] production [94, 95]. A compound known as dammara-20,24-dien-3-one was isolated from Chisocheton polyandrus and displayed good inhibition of both human 5-LOX and COX-2 . Flavonoids have been confirmed by in vitro studies to be able to suppress iNOS expression and to prevent nitric oxide production, depending on their structure or subclass of flavonoids for the strength level .
In overall, this review clearly demonstrates the potential of Malaysian medicinal plants as anti-inflammatory agents in which Melicope ptelefolia (Tenggek burung) and Portulaca oleracea (Gelang pasir) were found to exhibit potent anti-inflammatory activity in vitro. Pharmacological studies revealed that chemical diverse groups of naturally occurring substances derived from the plants show promising anti-inflammatory activity. Therefore, this review suggests further research needs to be carried out on the bioactive compounds present in the particular plants which have a potential to treat an inflammation and the possible underlying mechanisms of inflammation.
Conflicts of Interest
The authors do not have any conflicts of interest regarding the content of the present work.
This research was financially supported by Universiti Tun Hussein Onn Malaysia (UTHM) (Vot No. U758, U673, and U908).
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Fazleen Izzany Abu Bakar (ID), (1,2) Mohd Fadzelly Abu Bakar (ID), (1,2) Norazlin Abdullah (ID), (1,2) Susi Endrini, (3) and Asmah Rahmat (1)
(1) Faculty of Applied Sciences and Technology, Universiti Tun Hussein Onn Malaysia (UTHM), Hab Pendidikan Tinggi Pagoh, KM 1, Jalan Panchor, 84600 Muar, Johor, Malaysia
(2) Centre of Research for Sustainable Uses of Natural Resources (CoR-SUNR), Universiti Tun Hussein Onn Malaysia (UTHM), Parit Raja, 86400 Batu Pahat, Johor, Malaysia
(3) Faculty of Medicine, YARSI University, 10510 Jakarta, Indonesia
Correspondence should be addressed to Mohd Fadzelly Abu Bakar; email@example.com
Received 30 January 2018; Revised 25 April 2018; Accepted 20 May 2018; Published 9 July 2018
Academic Editor: Mohammad A. Rashid
Table 1: The medicinal plants which are considered to possess anti- inflammatory activity based on in vitro studies. Scientific Family Local name name Agelaea Connaraceae Akar rusa-rusa borneensis Anacardium Anacardiaceae Pokok gajus occidentale Averrhoa Oxalidaceae Belimbing buluh bilimbi Barringtonia Lecythidaceae Putat kampung racemosa Boesenbergia Zingiberaceae Temu kunci rotunda Boswellia Burseraceae Salai guggul and serrata kemenyan Buchanania Anacardiaceae Tais/mangga insignis hutan Canarium Burseraceae Kedondong and patentinervium kaju kedapak Carica papaya Caricaceae Betik Chisocheton Meliaceae Lisi-lisi polyandrus Citrullus Cucurbitaceae Tembikai lanatus Cosmos Asteraceae Ulam raja caudatus Crinum Amaryllidaceae Pokok bakung asiaticum Curcuma longa Zingiberaceae Kunyit Curcuma Zingiberaceae Temu mangga mangga Cythostema Annonaceae Lianas excelsia Desmos Annonaceae Kenanga hutan chinensis Eurycoma Simaroubaceae Tongkat ali longifolia Ficus deltoidea Moraceae Mas cotek Garcinia Clusiaceae Asam kandis cuspidata Garcinia Guttiferae Pokok penanti subelliptica Gynura Asteraceae Pokok daun dewa pseudochina Jatropha curcas Euphorbiaceae Jarak pagar Kaempferia Zingiberaceae Cekur galanga Labisia pumila Myrsinaceae Kacip fatimah var. alata Leucas Lamiaceae Ketuinbak linifolia Litsea garciae Lauraceae Engkala/ pengalaban Melicope Rutaceae Tenggek burung ptelefolia Moringa Moringaceae Kelur oleifera Musa Musaceae Pisang abu nipah acuminata Ocimum Lamiaceae Daun selasih basilicum Ocim um Lamiaceae Kemangi putih canum Oenanthe Apiaceae Selom javanica Orthosiphon Lamiaceae Misai kucing stamineus Pandanus Pandanaceae Pandan amaryllifolius Persicaria Polygonaceae Daun kesum tenella Phaleria Thymelaeaceae Mahkota dewa macrocarpa Piper Piperaceae Kaduk sarmentosum Pithecellobium Fabaceae Medang confertum Portulaca Portulacaceae Gelang pasir oleracea Psophocarpus Fabaceae Kacang botol tetragonolobus Sauropus Phyllanthaceae Cekur manis androgynus Solanum Solanaceae Terung meranti nigrum Solanum Solanaceae Terung belanda torvum Thymus Lamiaceae Taim vulgaris Timonius Rubiaceae Batut flavescens Scientific Part/solvent Types of assays Anti- name used inflammatory activity (%) Agelaea Bark/methanol LOX inhibition 71%-100% at borneensis 100 [micro]g/ml Anacardium Leaves/methanol NO inhibition 16.10% at occidentale 250 [micro]g/ml Averrhoa Fruits/water NO inhibition 22.30% at bilimbi 250 [micro]g/ml Leaves/ 57.7% at chloroform 100 [micro]g/ml Barringtonia Leaves/ethanol Griess assay (NO 29.80% at racemosa inhibition) 100 [micro]g/ml Leaves/hexane 42.39% at 100 [micro]g/ml Boesenbergia Rhizomes/hexane Griess assay NA rotunda (nitrite determination) Boswellia Leaves/methanol Human red blood 80.00% at serrata cell method 2000 [micro]g/ml Buchanania Bark/methanol LOX inhibition 41%-70% at insignis 100 [micro]g/ml Canarium Leaves and 5-LOX inhibition NA patentinervium barks/hexane, chloroform, and ethanol Carica papaya Leaves/methanol Griess assay (NO 72.63% at inhibition) 100 [micro]g/ml Bark/methanol LOX inhibition 71%-100% at 100 [micro]g/ml Chisocheton Leaves/hexane, Soybean LOX NA polyandrus dichloromethane, inhibition and methanol assay Citrullus Fruit pulp/ COX-2 inhibitory 60-70% at lanatus petroleum ether, activity 100 [micro]M chloroform, and 90% ethanol Griess assay (NO inhibition) Cosmos Leaves/methanol NO inhibition 15.40% at caudatus 250 [micro]g/ml Crinum Leaves/ethanol NO inhibition NA asiaticum Curcuma longa Rhizomes/ COX-2 inhibitory 82.50% and hexane-ethyl activity 58.90% at acetate and 125 [micro]g/ml methanol Curcuma Rhizomes/ NO inhibition 19.20% at mangga methanol 250 [micro]g/ml Cythostema Leaves and LOX inhibition 41%-70% at excelsia stems/methanol 100 [micro]g/ml Desmos Bark/methanol LOX inhibition 41%-70% at chinensis 100 [micro]g/ml Eurycoma Root/ Human red blood 70.97% at longifolia hydroalcoholics cell membrane 1000 [micro]g/ml stabilization method Ficus deltoidea Leaves/methanol LOX inhibition 10.35% at 100 [micro]g/ml Garcinia Bark/methanol LOX inhibition 71%-100% at cuspidata 100 [micro]g/ml Garcinia Seeds/chloroform Chemical mediator NA subelliptica released from mast cell and neutrophil inhibition Gynura Leaves/ethyl IL-6/luciferase NA pseudochina acetate assay Jatropha curcas Latex and NO inhibition NA leaves/aqueous methanol Kaempferia Rhizomes/ COX-2 inhibitory 57.82% at galanga petroleum ether, screening assay 200 [micro]g/ml chloroform, methanol, and water Labisia pumila Roots/methanol Colorimetric 75.68% at var. alata nitric oxide 100 [micro]g/ml assay (macrophage line) cell Leucas Whole plant/ LOX inhibition 34% at linifolia methanol 100 [micro]g/ml LOX assay 9.42% at 2 mg/ml Litsea garciae Pruits/methanol Hyaluronidase 27.70% at assay 5 mg/ml Melicope Leaves/methanol NO inhibition 95% at ptelefolia 250 [micro]g/ml Soybean 15-LOX 72.3% inhibition assay Moringa Pruits/ethyl NO inhibition NA oleifera acetate Musa Flowering Griess assay (NO 71.06% at acuminata stalk/methanol inhibition) 100 [micro]g/ml Ocimum Leaves/methanol NO inhibition 30.00% at basilicum 250 [micro]g/ml Ocim um Whole plant/ LOX inhibition 32% at canum methanol 100 [micro]g/ml Oenanthe Whole plant/ Griess assay (NO 75.64% at javanica methanol inhibition) 100 [micro]g/ml Orthosiphon Leaves/petroleum NO inhibition NA stamineus ether, chloroform, and methanol Pandanus Leaves/methanol NO inhibition 34.10% at amaryllifolius 250 [micro]g/ml Persicaria Leaves/ methanol NO inhibition 87.80% at tenella 250 [micro]g/ml Mesocarp/ 69.50% at methanol 200 [micro]g/ml Phaleria Pericarp/ NO inhibition 63.40% at macrocarpa methanol 200 [micro]g/ml Seeds/methanol 38.10% at 200 [micro]g/ml Piper Leaves/ methanol Griess assay (NO 62.82% at sarmentosum inhibition) 100 [micro]g/ml Pithecellobium Seeds/methanol NO inhibition 23.50% at confertum 250 [micro]g/ml Portulaca Leaves/ methanol NO inhibition 94.80% at oleracea 250 [micro]g/ml Psophocarpus Pod/methanol Griess assay (NO 39.28% at tetragonolobus inhibition) 100 [micro]g/ml Sauropus Leaves/ methanol Griess assay (NO 68.28% at androgynus inhibition) 100 [micro]g/ml Solanum Leaves/ methanol NO inhibition 27.60% at nigrum 250 [micro]g/ml Solanum Leaves and NO inhibition 25.20% at torvum fruits/methanol 250 [micro]g/ml Thymus Whole plant/ LOX inhibition 62% at vulgaris methanol 100 [micro]g/ml Timonius Leaves/ methanol LOX inhibition 71%-100% at flavescens 100 [micro]g/ml Scientific [IC.sub.50] Active References name compounds Agelaea NA NA  borneensis Anacardium NA NA  occidentale Averrhoa NA NA  bilimbi Barringtonia NA NA  racemosa Boesenbergia 36.68 Boesenbergin A  rotunda Boswellia NA NA  serrata Buchanania NA NA  insignis Canarium 1.76, Scopoletin  patentinervium [microg/m Carica papaya 60.18 NA  [micro]g/ml NA NA  Chisocheton 0.69 [micro]M Dammara-20,24-dien-  polyandrus and 3-one and 24- 1.11 [micro]M hydroxydammara- 20,25-dien-3-one Citrullus 69 [micro]M Cucurbitacin E  lanatus 17.6 [micro]M Cosmos NA NA  caudatus Crinum 58.5 [micro]g/ml NA  asiaticum Curcuma longa NA Monodemethoxycurcumin  and bisdemethoxycurcumin Curcuma NA NA  mangga Cythostema NA NA  excelsia Desmos NA NA  chinensis Eurycoma NA NA longifolia  Ficus deltoidea NA NA  Garcinia 28.3 [micro]g/ml NA  cuspidata Garcinia 15.6 [micro]M, Garsubellin A and  subelliptica 18.2 [micro]M, garcinielliptin oxide and 20.0 [micro]M Gynura 11.63 [micro]g/ NA  pseudochina ml Jatropha curcas 29.7 and NA  93.5 [micro]g/ml Kaempferia 0.83 [micro]M Ethyl-p-  galanga methoxycinnamate Labisia pumila NA NA  var. alata Leucas NA NA  linifolia NA NA  Litsea garciae Melicope NA p-O-geranylcoumaric [13, 45] ptelefolia acid, kokusaginine, and scoparone 0.136 [micro]g/ (1) 4-[(20-O-Acetyl- ml a-L 1.67 [micro]M rhamnosyloxy)benzyl] iso thiocyanate Moringa 2.66 [micro]M (2) 4-[(30-O-Acetyl-  oleifera a-L- rhamnosyloxy)benzyl] iso thiocyanate 2.71, [micro]M (3) 4-[(40-O-Acetyl- a-L- rhamnosyloxy)benzyl] iso thiocyanate Musa 42.24 NA  acuminata [micro]g/ml Ocimum NA NA  basilicum Ocim um NA NA  canum Oenanthe 54.12 NA  javanica [micro]g/ml Orthosiphon 5.2 [micro]M Eupatorin and  stamineus (eupatorin) sinensetin 9.2 ([micro]M (sinensetin) Pandanus NA NA  amaryllifolius Persicaria 8,[micro]g/ml NA  tenella Phaleria NA NA  macrocarpa Piper 60.24 NA  sarmentosum [micro]g/ml Pithecellobium NA NA  confertum Portulaca 44 [micro]g/ml NA  oleracea Psophocarpus >100, NA  tetragonolobus [micro]g/ml Sauropus 58.34 NA  androgynus [micro]g/ml Solanum NA NA  nigrum Solanum NA NA  torvum Thymus NA NA  vulgaris Timonius 8.9 [micro]g/ml NA  flavescens Table 2: The medicinal plants which are considered to possess anti- inflammatory activity based on in vivo studies. Scientific name Family Local name Part/solvent used Achyranthes Amaranthaceae Ara songsang Root/ethyl alcohol asp era Annona Annonaceae Durian Leaves/aqueous muricata belanda ethanol Ardisia crispa Myrsinaceae Mata pelandok Root/ethanol Atylosia Fabaceae Kara- Leaves/ethanol scarabaeoides kara/kacang kerara Citrullus Cucurbitaceae Tembikai Fruit pulp/ lanatus petroleum ether, chloroform, and 90% ethanol Corchorus Malvaceae Kancing baju Leaves/chloroform capsularis Crinum Amaryllidaceae Pokok bakung Leaves/methanol asiaticum Curcuma Zingiberaceae Temu hitam Rhizomes/chloroform, aeruginosa methanol, and water Curcuma longa Zingiberaceae Kunyit Rhizomes/water Cyathula Amaranthaceae Ketumbar Leaves/methanol prostrata Dicranopteris Gleicheniaceae Resam Leaves/chloroform linearis Ficus deltoidea Moraceae Mas cotek Whole plant/water Garcinia Guttiferae Pokok penanti Seeds/chloroform subelliptica Justicia Acanthaceae Daun rusa Root/methanol gendarussa Kaempferia Zingiberaceae Cekur Rhizomes/chloroform galanga Manilkara Sapotaceae Ciku Leaves/ethyl acetate zapota Mitragyna Rubiaceae Biak-biak and Leaves/methanol speciosa ketom Moringa Moringaceae Kelur Leaves/water oleifera Muntingia Muntingiaceae Kerukup siam Leaves/water calabura Orthosiphon Lamiaceae Misai kucing Leaves/methanol: stamineus water Peperomia Piperaceae Ketumpangan Whole plant/ pellucida air petroleum ether Phyllanthus Phyllanthaceae Cermai Leaves/methanol, acidus ethyl acetate, and petroleum ether Physalis Solanaceae Pokok letup- Whole plant/ minima letup methanol and chloroform fraction Piper Piperaceae Kaduk Leaves/water sarmentosum Polygonum Polygonaceae Kesum Aerial parts/water minus Sandoricum Meliaceae SentuI Stems/methanol koetjape Solanum Solanaceae Terung Leaves/water nigrum meranti Stachytarpheta Verbenaceae Selasih dandi Leaves/ethanol jamaicensis Vitex negundo Lamiaceae Legundi Leaves/ethanol Zingiber Zingiberaceae Lempoyang Rhizomes/ methanol zerumbet Scientific name Dose of the extract Experimental animals Achyranthes 50, 100, and 200 Wistar rats asp era mg/kg Annona 10-300 mg/kg Sprague-Dawley rats muricata Ardisia crispa 3, 10, 30, 100, and Sprague-Dawley rats 300 mg/kg of body weight Atylosia 150, 300, and 450 Swiss albino mice scarabaeoides mg/kg Citrullus 30 and 60 mg/kg of BALB/c mice lanatus body weight Corchorus 20, 100, and 200 BALB-c mice and capsularis mg/kg Sprague-Dawley rats Crinum 50 mg/kg of the Mice asiaticum extract Curcuma 100, 200, 400, and Swiss mice and aeruginosa 800 mg/kg Wistar rats Curcuma longa 200 mg/kg of body Wistar albino rats weight Cyathula 50,100, and 200 Wistar rats and prostrata mg/kg Swiss albino mice Dicranopteris 10, 100, and 200 BALB-c mice and linearis mg/kg Sprague-Dawley rats Ficus deltoidea 30, 100, and 300 Sprague-Dawley rats mg/kg Garcinia 3, 10, 30, 50, and Sprague-Dawley rats subelliptica 100 [micro]M Justicia 50 mg/kg of the Wistar rats gendarussa extract Kaempferia 2 g/kg of the Male Sprague-Dawley galanga extract rats Manilkara 300 mg/kg of body Albino Wistar rats zapota weight Mitragyna 50, 100, and 200 Sprague-Dawley rats speciosa mg/kg Moringa 10, 30, and 100 BALB-c mice and oleifera mg/kg Sprague-Dawley rats Muntingia 27 mg/kg, 135 mg/kg, Sprague-Dawley rats calabura and 270 mg/kg Orthosiphon 125, 250, 500, and Charles River mice stamineus 1000 mg/kg and Sprague-Dawley rats Peperomia 1000 mg/kg Sprague-Dawley rats pellucida Phyllanthus 250 and 500 mg/kg Wistar rats and acidus albino mice Physalis 200 and 400 mg/kg NMRI mice and Wistar minima rats Piper 30-300 mg/kg of the Sprague/Dawley rats sarmentosum extract and male BALB/c mice Polygonum 100mg/kg and Wistar albino rats minus 300 mg/kg Sandoricum 5 mg/ear BALB/c mice koetjape Solanum 10, 50, and 100% of BALB-c mice and nigrum concentration Sprague-Dawley rats Stachytarpheta 50, 100, and 150 BALB-c albino strain jamaicensis mg/kg mice and Sprague- Dawley rats Vitex negundo 2 mg/ear Mice Zingiber 25, 50, and BALB/c mice zerumbet 100mg/kg 5, 10, 50, and ICR mice 100mg/kg Scientific name Results References Achyranthes All the doses caused significant  asp era reduction in paw edema compared to control Annona A significant decrease of the  muricata concentration of the proinflammatory cytokines TNF-[alpha] and IL-1[beta] was observed Ardisia crispa A significant inhibition (93.34%)  was observed in carrageenan- induced edema in rats at a dose of 300 mg/kg Atylosia The extract displayed significant  scarabaeoides inhibition of inflammation. Highest inhibition of paw edema (38.38%) at a dose of 450 mg/kg after 4h of administration Citrullus Cucurbitacin E inhibits  lanatus inflammation significantly from the fourth hour and is able to revert paw edema through the COX-2 inhibition Corchorus The extract caused significant  capsularis reduction in the thickness of edematous paw for the first 6h Crinum Inhibition of paw edema (94.8%)  asiaticum Curcuma No significant suppression was  aeruginosa observed after oral administration of all doses on carrageenan-induced paw edema Curcuma longa The production of anti-  inflammatory/proinflammatory cytokines is decreasing Cyathula All extracts displayed  prostrata a significant dose-dependent inhibition in the carrageenan-, arachidonic acid-, and xylene- induced tests Dicranopteris The extract produced significant  linearis anti-inflammatory activity that did not depend on the doses of the extract Ficus deltoidea The rats' paw edema volume  reduced significantly in a dose- dependent manner Garcinia A potent inhibitory effect on  subelliptica fMLP/CB-induced superoxide anion generation was observed in the isolated compound garcinielliptin oxide Justicia 80% and 93% edema inhibition  gendarussa at the third and fifth hours Kaempferia Highest edema inhibition  galanga (42.9%) Manilkara Inhibition of paw edema  zapota (92.41%) Mitragyna Both doses of 100 and 200 mg/kg  speciosa showed a significant inhibition of the paw edema (63%) Moringa Highest edema inhibition oleifera (66.7%) at the second hour at  100 mg/kg of dose Muntingia The extract was found to exhibit  calabura a concentration-independent anti-inflammatory activity Orthosiphon Increase in edema inhibition  stamineus (26.79%) Peperomia The extract showed significant  pellucida inhibition in magnitude of swelling after 4 h of administration Phyllanthus All the extracts showed  acidus reduction in carrageenan- induced paw edema with highest inhibition (90.91%) in the methanol extract Physalis Crude extract and chloroform  minima fraction showed highest inhibition of paw edema at 66% and 68% at 400 mg/kg, respectively Piper All doses exerted anti-  sarmentosum inflammatory activity in a dose- dependent manner Polygonum The extracts significantly  minus reduced the paw edema volume in the rats after 4 h Sandoricum A significant inhibition (94%) in  koetjape TPA-induced edema was observed in the isolated compound 3-oxo-12-oleanen- 29-oic acid Solanum Extracts produce apparently  nigrum two-phase anti-inflammatory activity: the first phase between 1 and 2 h and the second phase between 5 and 7h after carrageenan administration Stachytarpheta A significant dose-dependent  jamaicensis anti-inflammatory activity was observed 30 min after the administration of the extract at all doses Vitex negundo The extract showed an inhibitory  activity of 54.1% Zingiber A significant antiedema activity  zerumbet was observed at all doses in a dose-dependent manner (i.e., 50 and 100 mg/kg doses of the extract exhibited activity at 90 min after administration, while 25 mg/kg exhibited at 150 min) The isolated compound  (zerumbone) significantly showed dose-dependent inhibition of paw edema induced by carrageenan at all doses (5, 10, 50, and 100mg/kg) in mice with percentage of inhibition of 33.3, 66.7, 83.3, and 83.3%, respectively
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|Author:||Bakar, Fazleen Izzany Abu; Bakar, Mohd Fadzelly Abu; Abdullah, Norazlin; Endrini, Susi; Rahmat, Asma|
|Publication:||Advances in Pharmacological Sciences|
|Date:||Jan 1, 2018|
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