Advances in Pharmacological and Pharmaceutical Sciences

Advances in Pharmacological and Pharmaceutical Sciences / 2018 / Article

Review Article | Open Access

Volume 2018 |Article ID 8603602 | 13 pages |

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

Academic Editor: Mohammad A. Rashid
Received30 Jan 2018
Revised25 Apr 2018
Accepted20 May 2018
Published09 Jul 2018


This article aims to provide detailed information on Malaysian plants used for treating inflammation. An extensive search on electronic databases including PubMed, Google Scholar, Scopus, and ScienceDirect and conference papers was done to find relevant articles on anti-inflammatory activity of Malaysian medicinal plants. The keyword search terms used were “inflammation,” “Malaysia,” “medicinal plants,” “mechanisms,” “in vitro,” and “in vivo.” As a result, 96 articles on anti-inflammatory activity of Malaysian medicinal plants were found and further reviewed. Forty-six (46) plants (in vitro) and 30 plants (in vivo) have been identified to possess anti-inflammatory activity where two plants, Melicope ptelefolia (Tenggek burung) and Portulaca oleracea (Gelang pasir), were reported to have the strongest anti-inflammatory activity of more than 90% at a concentration of 250 µg/ml. It was showed that the activity was mainly due to the occurrence of diverse naturally occurring phytochemicals from diverse groups such as flavonoids, coumarins, alkaloids, steroids, benzophenone, triterpenoids, curcuminoids, and cinnamic acid. Hence, this current review is a detailed discussion on the potential of Malaysian medicinal plants as an anti-inflammatory agent from the previous studies. However, further investigation on the possible underlying mechanisms and isolation of active compounds still remains to be investigated.

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 E2 (PGE2) as well as proinflammatory cytokines (i.e., tumour necrosis factor-alpha (TNF-α) 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.

Scientific nameFamilyLocal namePart/solvent usedTypes of assaysAnti-inflammatory activity (%)IC50Active compoundsReferences

Agelaea borneensisConnaraceaeAkar rusa-rusaBark/methanolLOX inhibition71%–100% at 100 μg/mlNANA[26]
Anacardium occidentaleAnacardiaceaePokok gajusLeaves/methanolNO inhibition16.10% at 250 μg/mlNANA[13]
Averrhoa bilimbiOxalidaceaeBelimbing buluhFruits/waterNO inhibition22.30% at 250 μg/mlNANA[13]
Barringtonia racemosaLecythidaceaePutat kampungLeaves/chloroformGriess assay (NO inhibition)57.7% at 100 μg/mlNANA[27]
Leaves/ethanol29.80% at 100 μg/ml
Leaves/hexane42.39% at 100 μg/ml
Boesenbergia rotundaZingiberaceaeTemu kunciRhizomes/hexaneGriess assay (nitrite determination)NA36.68 μMBoesenbergin A[28]
Boswellia serrataBurseraceaeSalai guggul and kemenyanLeaves/methanolHuman red blood cell method80.00% at 2000 μg/mlNANA[29]
Buchanania insignisAnacardiaceaeTais/mangga hutanBark/methanolLOX inhibition41%–70% at 100 μg/mlNANA[26]
Canarium patentinerviumBurseraceaeKedondong and kaju kedapakLeaves and barks/hexane, chloroform, and ethanol5-LOX inhibitionNA1.76 μMScopoletin[30]
Carica papayaCaricaceaeBetikLeaves/methanolGriess assay (NO inhibition)72.63% at 100 μg/ml60.18 μg/mlNA[31]
Chisocheton polyandrusMeliaceaeLisi-lisiBark/methanolLOX inhibition71%–100% at 100 μg/mlNANA[26]
Leaves/hexane, dichloromethane, and methanolSoybean LOX inhibition assayNA0.69 μM and 1.11 μMDammara-20,24-dien-3-one and 24-hydroxydammara-20,25-dien-3-one[32]
Citrullus lanatusCucurbitaceaeTembikaiFruit pulp/petroleum ether, chloroform, and 90% ethanolCOX-2 inhibitory activity60–70% at 100 μM69 μMCucurbitacin E[33]
Griess assay (NO inhibition)17.6 μM
Cosmos caudatusAsteraceaeUlam rajaLeaves/methanolNO inhibition15.40% at 250 μg/mlNANA[13]
Crinum asiaticumAmaryllidaceaePokok bakungLeaves/ethanolNO inhibitionNA58.5 μg/mlNA[34]
Curcuma longaZingiberaceaeKunyitRhizomes/hexane-ethyl acetate and methanolCOX-2 inhibitory activity82.50% and 58.90% at 125 μg/mlNAMonodemethoxycurcumin and bisdemethoxycurcumin[35]
Curcuma manggaZingiberaceaeTemu manggaRhizomes/methanolNO inhibition19.20% at 250 μg/mlNANA[13]
Cythostema excelsiaAnnonaceaeLianasLeaves and stems/methanolLOX inhibition41%–70% at 100 μg/mlNANA[26]
Desmos chinensisAnnonaceaeKenanga hutanBark/methanolLOX inhibition41%–70% at 100 μg/mlNANA[26]
Eurycoma longifoliaSimaroubaceaeTongkat aliRoot/hydroalcoholicsHuman red blood cell membrane stabilization method70.97% at 1000 μg/mlNANA[36]
Ficus deltoideaMoraceaeMas cotekLeaves/methanolLOX inhibition10.35% at 100 μg/mlNANA[37]
Garcinia cuspidataClusiaceaeAsam kandisBark/methanolLOX inhibition71%–100% at 100 μg/ml28.3 μg/mlNA[26]
Garcinia subellipticaGuttiferaePokok penantiSeeds/chloroformChemical mediator released from mast cell and neutrophil inhibitionNA15.6 μM, 18.2 μM, and 20.0 μMGarsubellin A and garcinielliptin oxide[38]
Gynura pseudochinaAsteraceaePokok daun dewaLeaves/ethyl acetateIL-6/luciferase assayNA11.63 μg/mlNA[39]
Jatropha curcasEuphorbiaceaeJarak pagarLatex and leaves/aqueous methanolNO inhibitionNA29.7 and 93.5 μg/mlNA[40]
Kaempferia galangaZingiberaceaeCekurRhizomes/petroleum ether, chloroform, methanol, and waterCOX-2 inhibitory screening assay57.82% at 200 μg/ml0.83 μMEthyl-p-methoxycinnamate[41]
Labisia pumila var. alataMyrsinaceaeKacip fatimahRoots/methanolColorimetric nitric oxide assay (macrophage cell line)75.68% at 100 μg/mlNANA[42]
Leucas linifoliaLamiaceaeKetumbakWhole plant/methanolLOX inhibition34% at 100 μg/mlNANA[43]
Litsea garciaeLauraceaeEngkala/pengalabanFruits/methanolLOX assay9.42% at 2 mg/mlNANA[44]
Hyaluronidase assay27.70% at 5 mg/ml
Melicope ptelefoliaRutaceaeTenggek burungLeaves/methanolNO inhibition95% at 250 μg/mlNAp-O-geranylcoumaric acid, kokusaginine, and scoparone[13, 45]
Soybean 15-LOX inhibition assay72.3%
Moringa oleiferaMoringaceaeKelurFruits/ethyl acetateNO inhibitionNA0.136 μg/ml
1.67 μM
(1) 4-[(20-O-Acetyl-α-L rhamnosyloxy)benzyl]isothiocyanate[46]
2.66 μM(2) 4-[(30-O-Acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate
2.71 μM(3) 4-[(40-O-Acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate
Musa acuminataMusaceaePisang abu nipahFlowering stalk/methanolGriess assay (NO inhibition)71.06% at 100 μg/ml42.24 μg/mlNA[31]
Ocimum basilicumLamiaceaeDaun selasihLeaves/methanolNO inhibition30.00% at 250 μg/mlNANA[13]
Ocimum canumLamiaceaeKemangi putihWhole plant/methanolLOX inhibition32% at 100 μg/mlNANA[43]
Oenanthe javanicaApiaceaeSelomWhole plant/methanolGriess assay (NO inhibition)75.64% at 100 μg/ml54.12 μg/mlNA[31]
Orthosiphon stamineusLamiaceaeMisai kucingLeaves/petroleum ether, chloroform, and methanolNO inhibitionNA5.2 μM (eupatorin)
9.2 μM (sinensetin)
Eupatorin and sinensetin[47]
Pandanus amaryllifoliusPandanaceaePandanLeaves/methanolNO inhibition34.10% at 250 μg/mlNANA[13]
Persicaria tenellaPolygonaceaeDaun kesumLeaves/methanolNO inhibition87.80% at 250 μg/ml8 μg/mlNA[13]
Phaleria macrocarpaThymelaeaceaeMahkota dewaMesocarp/methanolNO inhibition69.50% at 200 μg/mlNANA[48]
Pericarp/methanol63.40% at 200 μg/ml
Seeds/methanol38.10% at 200 μg/ml
Piper sarmentosumPiperaceaeKadukLeaves/methanolGriess assay (NO inhibition)62.82% at 100 μg/ml60.24 μg/mlNA[31]
Pithecellobium confertumFabaceaeMedangSeeds/methanolNO inhibition23.50% at 250 μg/mlNANA[13]
Portulaca oleraceaPortulacaceaeGelang pasirLeaves/methanolNO inhibition94.80% at 250 μg/ml44 μg/mlNA[13]
Psophocarpus tetragonolobusFabaceaeKacang botolPod/methanolGriess assay (NO inhibition)39.28% at 100 μg/ml>100 μg/mlNA[31]
Sauropus androgynusPhyllanthaceaeCekur manisLeaves/methanolGriess assay (NO inhibition)68.28% at 100 μg/ml58.34 μg/mlNA[31]
Solanum nigrumSolanaceaeTerung merantiLeaves/methanolNO inhibition27.60% at 250 μg/mlNANA[13]
Solanum torvumSolanaceaeTerung belandaLeaves and fruits/methanolNO inhibition25.20% at 250 μg/mlNANA[13]
Thymus vulgarisLamiaceaeTaimWhole plant/methanolLOX inhibition62% at 100 μg/mlNANA[43]
Timonius flavescensRubiaceaeBatutLeaves/methanolLOX inhibition71%–100% at 100 μg/ml8.9 μg/mlNA[26]

Scientific nameFamilyLocal namePart/solvent usedDose of the extractExperimental animalsResultsReferences

Achyranthes asperaAmaranthaceaeAra songsangRoot/ethyl alcohol50, 100, and 200 mg/kgWistar ratsAll the doses caused significant reduction in paw edema compared to control[49]
Annona muricataAnnonaceaeDurian belandaLeaves/aqueous ethanol10–300 mg/kgSprague-Dawley ratsA significant decrease of the concentration of the proinflammatory cytokines TNF-α and IL-1β was observed[50]
Ardisia crispaMyrsinaceaeMata pelandokRoot/ethanol3, 10, 30, 100, and 300 mg/kg of body weightSprague-Dawley ratsA significant inhibition (93.34%) was observed in carrageenan-induced edema in rats at a dose of 300 mg/kg[51]
Atylosia scarabaeoidesFabaceaeKara-kara/kacang keraraLeaves/ethanol150, 300, and 450 mg/kgSwiss albino miceThe extract displayed significant inhibition of inflammation. Highest inhibition of paw edema (38.38%) at a dose of 450 mg/kg after 4 h of administration[52]
Citrullus lanatusCucurbitaceaeTembikaiFruit pulp/petroleum ether, chloroform, and 90% ethanol30 and 60 mg/kg of body weightBALB/c miceCucurbitacin E inhibits inflammation significantly from the fourth hour and is able to revert paw edema through the COX-2 inhibition[33]
Corchorus capsularisMalvaceaeKancing bajuLeaves/chloroform20, 100, and 200 mg/kgBALB/c mice and Sprague-Dawley ratsThe extract caused significant reduction in the thickness of edematous paw for the first 6 h[53]
Crinum asiaticumAmaryllidaceaePokok bakungLeaves/methanol50 mg/kg of the extractMiceInhibition of paw edema (94.8%)[54]
Curcuma aeruginosaZingiberaceaeTemu hitamRhizomes/chloroform, methanol, and water100, 200, 400, and 800 mg/kgSwiss mice and Wistar ratsNo significant suppression was observed after oral administration of all doses on carrageenan-induced paw edema[55]
Curcuma longaZingiberaceaeKunyitRhizomes/water200 mg/kg of body weightWistar albino ratsThe production of anti-inflammatory/proinflammatory cytokines is decreasing[56]
Cyathula prostrataAmaranthaceaeKetumbarLeaves/methanol50,100, and 200 mg/kgWistar rats and Swiss albino miceAll extracts displayed a significant dose-dependent inhibition in the carrageenan-, arachidonic acid-, and xylene-induced tests[57]
Dicranopteris linearisGleicheniaceaeResamLeaves/chloroform10, 100, and 200 mg/kgBALB/c mice and Sprague-Dawley ratsThe extract produced significant anti-inflammatory activity that did not depend on the doses of the extract[58]
Ficus deltoideaMoraceaeMas cotekWhole plant/water30, 100, and 300 mg/kgSprague-Dawley ratsThe rats’ paw edema volume reduced significantly in a dose-dependent manner[59]
Garcinia subellipticaGuttiferaePokok penantiSeeds/chloroform3, 10, 30, 50, and 100 µMSprague-Dawley ratsA potent inhibitory effect on fMLP/CB-induced superoxide anion generation was observed in the isolated compound garcinielliptin oxide[38]
Justicia gendarussaAcanthaceaeDaun rusaRoot/methanol50 mg/kg of the extractWistar rats80% and 93% edema inhibition at the third and fifth hours[60]
Kaempferia galangaZingiberaceaeCekurRhizomes/chloroform2 g/kg of the extractMale Sprague-Dawley ratsHighest edema inhibition (42.9%)[41]
Manilkara zapotaSapotaceaeCikuLeaves/ethyl acetate300 mg/kg of body weightAlbino Wistar ratsInhibition of paw edema (92.41%)[61]
Mitragyna speciosaRubiaceaeBiak-biak and ketomLeaves/methanol50, 100, and 200 mg/kgSprague-Dawley ratsBoth doses of 100 and 200 mg/kg showed a significant inhibition of the paw edema (63%)[62]
Moringa oleiferaMoringaceaeKelurLeaves/water10, 30, and 100 mg/kgBALB/c mice and Sprague-Dawley ratsHighest edema inhibition (66.7%) at the second hour at 100 mg/kg of dose[63]
Muntingia calaburaMuntingiaceaeKerukup siamLeaves/water27 mg/kg, 135 mg/kg, and 270 mg/kgSprague-Dawley ratsThe extract was found to exhibit a concentration-independent anti-inflammatory activity[64]
Orthosiphon stamineusLamiaceaeMisai kucingLeaves/methanol : water125, 250, 500, and 1000 mg/kgCharles River mice and Sprague-Dawley ratsIncrease in edema inhibition (26.79%)[65]
Peperomia pellucidaPiperaceaeKetumpangan airWhole plant/petroleum ether1000 mg/kgSprague-Dawley ratsThe extract showed significant inhibition in magnitude of swelling after 4 h of administration[66]
Phyllanthus acidusPhyllanthaceaeCermaiLeaves/methanol, ethyl acetate, and petroleum ether250 and 500 mg/kgWistar rats and albino miceAll the extracts showed reduction in carrageenan-induced paw edema with highest inhibition (90.91%) in the methanol extract[67]
Physalis minimaSolanaceaePokok letup-letupWhole plant/methanol and chloroform fraction200 and 400 mg/kgNMRI mice and Wistar ratsCrude extract and chloroform fraction showed highest inhibition of paw edema at 66% and 68% at 400 mg/kg, respectively[68]
Piper sarmentosumPiperaceaeKadukLeaves/water30–300 mg/kg of the extractSprague-Dawley rats and male BALB/c miceAll doses exerted anti-inflammatory activity in a dose-dependent manner[69]
Polygonum minusPolygonaceaeKesumAerial parts/water100 mg/kg and 300 mg/kgWistar albino ratsThe extracts significantly reduced the paw edema volume in the rats after 4 h[70]
Sandoricum koetjapeMeliaceaeSentulStems/methanol5 mg/earBALB/c miceA significant inhibition (94%) in TPA-induced edema was observed in the isolated compound 3-oxo-12-oleanen-29-oic acid[71]
Solanum nigrumSolanaceaeTerung merantiLeaves/water10, 50, and 100% of concentrationBALB/c mice and Sprague-Dawley ratsExtracts produce apparently two-phase anti-inflammatory activity: the first phase between 1 and 2 h and the second phase between 5 and 7 h after carrageenan administration[72]
Stachytarpheta jamaicensisVerbenaceaeSelasih dandiLeaves/ethanol50, 100, and 150 mg/kgBALB/c albino strain mice and Sprague-Dawley ratsA significant dose-dependent anti-inflammatory activity was observed 30 min after the administration of the extract at all doses[73]
Vitex negundoLamiaceaeLegundiLeaves/ethanol2 mg/earMiceThe extract showed an inhibitory activity of 54.1%[74]
Zingiber zerumbetZingiberaceaeLempoyangRhizomes/methanol25, 50, and 100 mg/kgBALB/c miceA significant antiedema activity 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)[75]
5, 10, 50, and 100 mg/kgICR miceThe isolated compound (zerumbone) significantly showed dose-dependent inhibition of paw edema induced by carrageenan at all doses (5, 10, 50, and 100 mg/kg) in mice with percentage of inhibition of 33.3, 66.7, 83.3, and 83.3%, respectively[76]

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-κB), 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) A4, LTB4, LTC4, LTD4, and LTE4 [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 Fe3+ to Fe2+, 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 anti-inflammatory 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 µg/ml, respectively [13]. Besides that, many previous studies had reported the plants which exerted anti-inflammatory activity between 70% and 80% at 100 µg/ml to 2000 µg/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), Carica papaya (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 µg/ml to 2000 µg/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 µg/ml [35]. Of the other study, Kaempferia galanga from the Zingiberaceae family exhibited moderate activity with 57.82% at 200 µg/ml where the isolated compound, ethyl-p-methoxycinnamate, 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 µg/ml [43], with the total phenolic content of 350 µg GAE/ml.

In this study, it was found that the results of anti-inflammatory 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 anti-inflammatory 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-γ/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-12-en-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 anti-inflammatory 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-α-L-rhamnosyloxy)benzyl]isothiocyanate, 4-[(30-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate, and 4-[(40-O-acetyl-α-L-rhamnosyloxy)benzyl]isothiocyanate [28, 30, 32, 33, 35, 38, 41, 4547]. 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-α 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.

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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