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A Review of Malaysian Medicinal Plants with Potential Anti-Inflammatory Activity.

1. Introduction

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 [1]. 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 [1]. 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 [4]. 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 [5].

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 [4]. However, the major concern is that NSAIDs may cause various side effects such as gastrointestinal complications [6]. 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 [9]. 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 [10]. In Malaysia, about 2000 medicinal plant species are reported to possess health benefit properties [11]. 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 [12] or age-related diseases [13]. 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.

2. Methods

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.

3. Discussion

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 [14] 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 [15]. 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 [18]. 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 [21]. For instance, chronic inflammation may lead to infectious diseases and cancer [22], 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 [25]. COX-2 (Vioxx) also has been reported to cause serious cardiovascular events [2]. 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 [77]. 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 [78]. 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 [79]. 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] [80], where LTB4 (one of the mediators of inflammation) is reported to be the most crucial in the inflammatory response [81]. 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 [84]. In 2011, Kwon et al. [85] 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 [26]. 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 [86]. Besides, the COX-2 gene is also a gene for iNOS induced during inflammation and cell growth [87]. 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 [13]. 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 [35]. 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 [41]. 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 [43], 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) [44]. 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 [35]. 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 [31].

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 [88]. It is also one of the conventional methods used to evaluate the anti-inflammatory effect of drugs or medicinal plants at the acute stage [89] 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 [92]. 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 [51]. 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%) [71].

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. [93] 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 [32]. 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 [96].

4. Conclusion

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.

https://doi.org/10.1155/2018/8603602

Conflicts of Interest

The authors do not have any conflicts of interest regarding the content of the present work.

Acknowledgments

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; fadzelly@uthm.edu.my

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               [26]
borneensis

Anacardium              NA                   NA               [13]
occidentale

Averrhoa                NA                   NA               [13]
bilimbi

Barringtonia            NA                   NA               [27]
racemosa

Boesenbergia          36.68            Boesenbergin A         [28]
rotunda

Boswellia               NA                   NA               [29]
serrata

Buchanania              NA                   NA               [26]
insignis

Canarium              1.76,              Scopoletin           [30]
patentinervium      [microg/m

Carica papaya         60.18                  NA               [31]
                   [micro]g/ml

                        NA                   NA               [26]

Chisocheton       0.69 [micro]M     Dammara-20,24-dien-       [32]
polyandrus             and             3-one and 24-
                  1.11 [micro]M       hydroxydammara-
                                      20,25-dien-3-one

Citrullus          69 [micro]M         Cucurbitacin E         [33]
lanatus

                  17.6 [micro]M

Cosmos                  NA                   NA               [13]
caudatus

Crinum           58.5 [micro]g/ml            NA               [34]
asiaticum

Curcuma longa           NA         Monodemethoxycurcumin      [35]
                                            and
                                    bisdemethoxycurcumin

Curcuma                 NA                   NA               [13]
mangga

Cythostema              NA                   NA               [26]
excelsia

Desmos                  NA                   NA               [26]
chinensis

Eurycoma                NA                   NA
longifolia                                                    [36]

Ficus deltoidea         NA                   NA               [37]

Garcinia         28.3 [micro]g/ml            NA               [26]
cuspidata

Garcinia          15.6 [micro]M,     Garsubellin A and        [38]
subelliptica      18.2 [micro]M,   garcinielliptin oxide
                       and
                  20.0 [micro]M

Gynura           11.63 [micro]g/             NA               [39]
pseudochina             ml

Jatropha curcas      29.7 and                NA               [40]
                 93.5 [micro]g/ml

Kaempferia        0.83 [micro]M           Ethyl-p-            [41]
galanga                               methoxycinnamate

Labisia pumila          NA                   NA               [42]
var. alata

Leucas                  NA                   NA               [43]
linifolia

                        NA                   NA               [44]

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-      [46]
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               [31]
acuminata          [micro]g/ml

Ocimum                  NA                   NA               [13]
basilicum

Ocim um                 NA                   NA               [43]
canum

Oenanthe              54.12                  NA               [31]
javanica           [micro]g/ml

Orthosiphon        5.2 [micro]M        Eupatorin and          [47]
stamineus          (eupatorin)           sinensetin
                  9.2 ([micro]M
                   (sinensetin)

Pandanus                NA                   NA               [13]
amaryllifolius

Persicaria        8,[micro]g/ml              NA               [13]
tenella

Phaleria                NA                   NA               [48]
macrocarpa

Piper                 60.24                  NA               [31]
sarmentosum        [micro]g/ml

Pithecellobium          NA                   NA               [13]
confertum

Portulaca         44 [micro]g/ml             NA               [13]
oleracea

Psophocarpus          >100,                  NA               [31]
tetragonolobus     [micro]g/ml

Sauropus              58.34                  NA               [31]
androgynus         [micro]g/ml

Solanum                 NA                   NA               [13]
nigrum

Solanum                 NA                   NA               [13]
torvum

Thymus                  NA                   NA               [43]
vulgaris

Timonius         8.9 [micro]g/ml             NA               [26]
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         [49]
asp era                   reduction in paw edema
                           compared to control

Annona                A significant decrease of the           [50]
muricata                   concentration of the
                        proinflammatory cytokines
                 TNF-[alpha] and IL-1[beta] was observed

Ardisia crispa      A significant inhibition (93.34%)         [51]
                       was observed in carrageenan-
                     induced edema in rats at a dose
                               of 300 mg/kg

Atylosia            The extract displayed significant         [52]
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              [33]
lanatus              inflammation significantly from
                      the fourth hour and is able to
                       revert paw edema through the
                             COX-2 inhibition

Corchorus             The extract caused significant          [53]
capsularis            reduction in the thickness of
                      edematous paw for the first 6h

Crinum               Inhibition of paw edema (94.8%)          [54]
asiaticum

Curcuma               No significant suppression was          [55]
aeruginosa                 observed after oral
                      administration of all doses on
                         carrageenan-induced paw
                                  edema

Curcuma longa            The production of anti-              [56]
                       inflammatory/proinflammatory
                         cytokines is decreasing

Cyathula                  All extracts displayed              [57]
prostrata              a significant dose-dependent
                     inhibition in the carrageenan-,
                      arachidonic acid-, and xylene-
                              induced tests

Dicranopteris        The extract produced significant         [58]
linearis             anti-inflammatory activity that
                      did not depend on the doses of
                               the extract

Ficus deltoidea         The rats' paw edema volume            [59]
                     reduced significantly in a dose-
                             dependent manner

Garcinia              A potent inhibitory effect on           [38]
subelliptica            fMLP/CB-induced superoxide
                      anion generation was observed
                         in the isolated compound
                          garcinielliptin oxide

Justicia               80% and 93% edema inhibition           [60]
gendarussa             at the third and fifth hours

Kaempferia               Highest edema inhibition             [41]
galanga                          (42.9%)

Manilkara                Inhibition of paw edema              [61]
zapota                           (92.41%)

Mitragyna            Both doses of 100 and 200 mg/kg          [62]
speciosa             showed a significant inhibition
                          of the paw edema (63%)

Moringa                  Highest edema inhibition
oleifera              (66.7%) at the second hour at           [63]
                            100 mg/kg of dose

Muntingia            The extract was found to exhibit         [64]
calabura               a concentration-independent
                        anti-inflammatory activity

Orthosiphon            Increase in edema inhibition           [65]
stamineus                        (26.79%)

Peperomia             The extract showed significant          [66]
pellucida               inhibition in magnitude of
                          swelling after 4 h of
                              administration

Phyllanthus              All the extracts showed              [67]
acidus                  reduction in carrageenan-
                      induced paw edema with highest
                        inhibition (90.91%) in the
                             methanol extract

Physalis               Crude extract and chloroform           [68]
minima                   fraction showed highest
                      inhibition of paw edema at 66%
                          and 68% at 400 mg/kg,
                               respectively

Piper                    All doses exerted anti-              [69]
sarmentosum          inflammatory activity in a dose-
                             dependent manner

Polygonum               The extracts significantly            [70]
minus                  reduced the paw edema volume
                          in the rats after 4 h

Sandoricum          A significant inhibition (94%) in         [71]
koetjape                  TPA-induced edema was
                         observed in the isolated
                        compound 3-oxo-12-oleanen-
                               29-oic acid

Solanum                Extracts produce apparently            [72]
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           [73]
jamaicensis           anti-inflammatory activity was
                        observed 30 min after the
                     administration of the extract at
                                all doses

Vitex negundo        The extract showed an inhibitory         [74]
                            activity of 54.1%

Zingiber             A significant antiedema activity         [75]
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               [76]
                        (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
Words:8661
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