|Year : 2017 | Volume
| Issue : 3 | Page : 164-170
α-Glucosidase inhibitory activity of selected Malaysian plants
Dzatil Awanis Mohd Bukhari1, Mohammad Jamshed Siddiqui1, Siti Hadijah Binti Shamsudin2, Md. Mukhlesur Rahman1, Siti Zaiton Mat So'ad1
1 Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, Indera Mahkota, Kuantan 25200, Pahang, Malaysia
2 Department of Pharmacy Practice, Kulliyyah of Pharmacy, International Islamic University Malaysia, Indera Mahkota, Kuantan 25200, Pahang, Malaysia
|Date of Web Publication||14-Sep-2017|
Mohammad Jamshed Siddiqui
Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, Indera Mahkota, Jalan Istana, Kuantan 25200, Pahang
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Diabetes is a common metabolic disease indicated by unusually high plasma glucose level that can lead to major complications such as diabetic neuropathy, retinopathy, and cardiovascular diseases. One of the effective therapeutic managements of the disease is to reduce postprandial hyperglycemia through inhibition of α-glucosidase, a carbohydrate-hydrolyzing enzyme to retard overall glucose absorption. In recent years, a plenty of research works have been conducted looking for novel and effective α-glucosidase inhibitors (AGIs) from natural sources as alternatives for the synthetic AGI due to their unpleasant side effects. Plants and herbs are rich with secondary metabolites that have massive pharmaceutical potential. Besides, studies showed that phytochemicals such as flavonoids, alkaloids, terpenoids, anthocyanins, glycosides, and phenolic compounds possess significant inhibitory activity against α-glucosidase enzyme. Malaysia is a tropical country that is rich with medicinal herbs. In this review, we focus on eight Malaysian plants with the potential as AGI to develop a potential functional food or lead compounds against diabetes.
Keywords: Diabetes, Malaysian plants, α-glucosidase inhibitor
|How to cite this article:|
Mohd Bukhari DA, Siddiqui MJ, Shamsudin SH, Rahman MM, So'ad SZ. α-Glucosidase inhibitory activity of selected Malaysian plants. J Pharm Bioall Sci 2017;9:164-70
|How to cite this URL:|
Mohd Bukhari DA, Siddiqui MJ, Shamsudin SH, Rahman MM, So'ad SZ. α-Glucosidase inhibitory activity of selected Malaysian plants. J Pharm Bioall Sci [serial online] 2017 [cited 2017 Oct 18];9:164-70. Available from: http://www.jpbsonline.org/text.asp?2017/9/3/164/214687
| Introduction|| |
Diabetes mellitus (DM) is a chronic, life-long condition that results in deficiency of overall insulin secretion or a reduced sensitivity of insulin-producing organs. Currently, DM is becoming one of the most expensive and worrisome chronic illnesses that keep escalating in numbers all over the world, particularly in low- and middle-income countries. Type 2 diabetes is increasing worldwide in epidemic proportions. Its associated morbidity and mortality is imposing a major burden on the healthcare system. The latest update from the World Health Organization shows that about 422 million people are having the disease, which is approximately a quadruple since 1980. In 2015, there were 3.3 million of diabetes cases in Malaysia.
α-Glucosidase inhibitor (AGI) is one of the antidiabetic drugs that are widely used and works efficiently in delaying the carbohydrates absorption from the small intestine to result in a reduced postprandial blood glucose and insulin levels. Examples of AGI in the current market include acarbose, miglitol, and voglibose. Due to the side effects of these synthetic AGIs (flatulence, bloating, stomach pain, and diarrhea), there is a demand of exploring novel AGI from natural sources as alternatives. A review by Kumar et al. revealed that AGI activity is possessed by plants' secondary metabolites such as flavonoids, alkaloids, terpenoids, anthocyanins, glycosides, curcuminoids, and phenolic compounds. Besides, studies also showed a strong correlation between total phenolic content (TPC) and AGI activity., A potent natural AGI kotalanol was isolated from the antidiabetic traditional Ayurvedic medicine (Salacia reticulata) and appeared to be more potent than acarbose.
Malaysia has a diverse range of herbal medicines that provide essential therapeutic benefits for locals. A plenty of works have been carried out on tropical plant extracts to prove its potential as antihyperglycemic agents, particularly as AGI. Furthermore, Agamuthu reported that about 1.2 million ton of agricultural waste including fruit peels and seeds was disposed into landfills every year. Therefore, the recycling of these wastes will be desirable to reduce the environmental impact following their disposal.
This review will be focusing on the potential of eight Malaysia plants (Garcinia mangostana, Nephelium lappaceum L., Barringtonia racemosa, Phyllanthus acidus, Cynometra cauliflora, Myristica fragrans, Cosmos caudatus, and Orthosiphon stamineus) possessing AGI activity. Three main aspects will be covered in this review; extraction and isolation methods of bioactive compounds, AGI assay protocols, and the potency of plant extract as AGI.
| Garcinia mangostana (Guttiferae)|| |
G. mangostana (mangosteen) is naturally growing in Southeast Asian nations – Malaysia, Indonesia, Sri Lanka, Philippines, Myanmar, and Thailand. In Malaysia, it is locally known as manggis, mesetor, semetah, or sementah. On average, the tree can slowly grow to a range of 6–25 m in height. The fruits are of round-shaped in dark-purple to red-purple with rind's thickness of 6–10 mm and white juicy flesh. The fruit is traditionally used to heal various illnesses including infections, wounds, diarrhea, and gastrointestinal disorder.
A study by Ryu et al. was conducted to evaluate the potential of AGI activity of G. mangostana extract and its isolated compounds. The study disclosed that the xanthone backbone is a potent molecular basis for AGI mechanism. Seedcases (10 g) of the plant collected in Vietnam were extracted with 200 ml of solvent by shaking at 30°C for 3 days before being evaporated under reduced pressure. Ethanolic extract showed the highest extraction yield (14.2%) of AGI, followed by 50% ethanol (13.7%), water (10.6%), and chloroform (4.9%). Extracts obtained were later subjected to isolation using silica gel column with hexane and acetone as eluent.
The in vitro assay was performed according to Kim et al. method. All the assessed compounds showed remarkable α-glucosidase inhibition (IC50 1.5–58.8 μM), more potent than the conventional AGI deoxynojirimycin (IC50 68.8 μM). In addition, in vivo test of ethanolic xanthone extract was carried out in hyperglycemic rats. The ethanol extract (100 mg/kg BW) showed a significant hypoglycemic impact after 30 min of oral maltose administration, and it was sustained up to 2 h which was similar to the reaction set out by the reference drug, acarbose.
| Nephelium lappaceum L. (Sapindaceae)|| |
N. lappaceum L. (rambutan) is one of the valued plant species in Southeast Asia, widely cultivated in Malaysia, Indonesia, Thailand, and Philippines. Rambutan trees grow in warm, wet, and lowland areas into distinct feature of red or yellow hairy skin. Different part of the plant is well known at its respective medicinal benefits. Malay population uses decoction of rambutan roots to relieve fever. The fruit is traditionally used as anthelmintic to eradicate intestinal worms, whereas the leaves are believed to cure headaches.
It was reported that the major component in N. lappaceum rind extracts is geraniin, an ellagitannin with an approximate dry weight of 3.79% (37.9 mg/g of the crude extract)., Palanisamy et al. had extracted the N. lappaceum rind with water and ethanol, and it was found that the ethanolic extracts procured a higher yield as opposed to the aqueous extract (ethanol 17.8%, aqueous 13.2%). In addition, incorporation of milling process in the extraction has significantly increased the yield by approximately 77% and 87% in the aqueous and ethanol extracts, respectively (ethanol 33.2%, aqueous 23.4%). However, both rind extracts exhibited significant AGI activity when compared with acarbose. In addition, promising AGI activity of geraniin had been observed in an in vitro study with IC50 0.92 μg/ml, lower than acarbose (IC50 25 μg/ml), the positive control.
Other than fruit peels, rambutan seeds also contain a variety of phenolic compounds such as ellagic acid, corilagin, and geraniin. In one of the studies by Soeng et al., rambutan seeds extract and fractions have shown to possess a significant inhibitory impact on α-glucosidase enzyme in vitro compared to drug acarbose. The extraction of rambutan seeds was performed using the maceration method and then fractioned using four partitioning solvents (hexane, ethyl acetate, butanol, and water).
A modified Farnsworth method was implemented as the phytochemical assay to test the rambutan seeds extract and fraction. The assay showed that the 70% ethanolic extract contained a moderate content of terpenoids, whereas other fractions (hexane, ethyl acetate, butanol, and water) contained a much lower content. Phenol is found in all extracts and fractions, except in the water fraction. The most potent α-glucosidase activity was demonstrated by the seeds ethanolic extract at the dose of 50 μg/ml.
| Barringtonia racemosa (Lecythidaceae)|| |
B. racemosa is an unexceptional mangrove tree species that grow in Bangladesh, Sri Lanka, India, Singapore, Malaysia, Madagascar, Thailand, Laos, Southern China, and Northern Australia. It is locally known as putat and fish poison tree or powder puff tree. Nearly all parts of this plant possess bioactivity against various illnesses, including seeds (colic, ophthalmic disorders, and antitumor), stem bark (mitogenic activity), bark and leaves (rat-snake bites, rat poisoning, and gastric ulcer), and roots (antibacterial).,,
Gowri et al. investigated the inhibitory activity of plant seeds extract against yeast and intestinal α-glucosidase enzyme. The coarsely powdered dried seeds (Kerala, India) were extracted using percolation method with hexane, ethanol, and methanol at ambient temperature for 4 days, followed by activity screening against the enzyme. Methanol extract showed the most potent inhibitory activity against α-glucosidase enzyme. Hence, the isolation was done on the methanol extract, which was subjected to vacuum liquid chromatography over a column of silica gel.
Bartogenic acid was isolated as the prime compound of the methanol extract. Despite that, the enzyme inhibition showed by isolated bartogenic acid alone was significantly less than the methanol extract (P < 0.03). The experimental outcomes showed that methanol extract had the most potent AGI activity (IC50 26.96 μg/ml), followed by the hexane (IC50 131.68 μg/ml) and ethanol extracts (IC50 163.67 μg/ml). As for the activity of isolated bartogenic acid alone, it was found to be less than all crude extracts; IC50 198.09 μg/ml.
Another study by Sulaiman and Ooi had determined that the juices from B. racemosa flesh possessed significant AGI activity with the inhibition percentage of approximately 94%. This result was correspondent to its high TPC (>600 μg gallic acid equivalent/g sample). Other than that, the same study also revealed the highest antioxidant activity by the plant fruit juice through ferric reducing antioxidant power and α,α-diphenyl-β-picrylhydrazyl assays. From the ultra-performance liquid chromatography (UPLC) chromatogram, ellagic acid, myricetin, and glycosidic quercetin were identified to be present in the fruit extract and the result was validated by comparing the peaks' retention times and ultraviolet spectra against the standards. Ellagic acid was discovered to be the major compound of the juice extract.
| Phyllanthus acidus (Phyllanthaceae)|| |
P. acidus (gooseberry) is widely distributed across Asia (India, Malaysia, Indonesia, Vietnam and Laos), parts of Central America, the Caribbean, and parts of South America., The plant has been used traditionally at treating pain, rheumatism, bronchitis, asthma, diabetes, gonorrhea, hypertension, etc.,, Many studies were conducted at determining the potential of each part of this plant, especially leaves, fruits, and roots.,,,,
A study by Ooi et al. had evaluated the AGI activity of P. acidus fruit extracts. 200 g of P. acidus fruits was washed with distilled water and later ground to obtain a fine puree (40 mesh or 400 μm of particle size). The puree was subjected into two groups – first group was soaked in distilled water (500 ml) for 15 min at room temperature and the second group was left undiluted. Both puree groups were then filtered using a clean muslin cloth and centrifuged for 15 min. Extraction was done in triplicate and the extract juices were stored at −10°C in the dark until further analysis.
The AGI activity of P. acidus juice extracts was evaluated according to the method by Ooi et al.P. acidus extract demonstrated the highest AGI percentage with 95.37% ± 0.15%. However, the value was not significantly different from other tested juices of B. racemosa, Cynometra cauliflora, M. fragrans, G. mangostana, Bouea macrophylla, Syzygium samarangense, and Citrus microcarpa. Previously, a very low AGI activity was discovered from P. acidus extract., On that account, the potent activity might be due to the presence of inhibitors in the juice compared to the extracts.
The separation of compounds in fruit extracts was carried out by UPLC that eventually identified gallic acid as the major compound in the extract that is responsible on the activity. Apart from that, several other flavonol and flavanone compounds were identified in the extracts chromatogram; myricetin, glycosidic quercetin, kaempferol, and glycosidic dihydroquercetin. In one of the studies, Jain and Singhai suggest that the aqueous extract of P. acidus leaves has significant hepatoprotective activity on acetaminophen- and thioacetamide-induced hepatotoxicity, which might be associated with its high phenolic and flavonoid content and antioxidant properties.
| Cynometra cauliflora (Fabaceae)|| |
C. cauliflora (namnam) is typically found in eastern and northern parts of Peninsular Malaysia, Southeast Asia, and India. Namnam leaves are traditionally used for treating diabetes and hyperlipidemia,, whereas fruits are used as cure for appetite loss. On the other hand, seed oil of plants is good for skin diseases.
Ado et al. had extracted the plant material by maceration technique in 100% methanol for 48 h at room temperature. After 48 h, the extract was decanted and fresh solvent was added to the plant residue for another cycle. This process was repeated several times. The extracts obtained were then concentrated under reduced pressure and the dried extract was stored at −20°C until further study.
The inhibitory activity against α-glucosidase enzyme was evaluated using modified method of Kim et al. The results showed that ethyl acetate and n-butanol extracts displayed the most potent inhibition compared to hexane, dichloromethane, and aqueous fractions, with IC50 values of 0.03 ± 0.004 and 0.044 ± 0.072 mg/ml, respectively. In addition, Pearson's correlation test showed a moderate correlation between TPC and AGI activity with an R2 = 0.417. This demonstrated the presence of nonphenolic compounds that were responsible for the enzyme inhibition. Besides that, it was presumed that the inhibitory activity was due to specific individual phenolic compound, rather than the overall phenolic content.
| Myristica fragrans L. (Myristicaceae)|| |
M. fragrans (nutmeg) is indigenous to Australia, Asia, and the tropical regions of Southeast Asia. Nutmeg is an expensive herb, often used as spice in cooking. The fruit consists of flesh, nutmeg, nut seed, and mace. Mace is normally used as flavoring agent and also traditionally consumed as the treatment for flatulence, vomiting, bladder and urinary tract inflammation, expectorant, and rheumatism.
The powdered M. fragrans fruits were extracted by Soxhlet extraction using methanol. The extract obtained was later filtered, concentrated under vacuum, and stored at −4°C until further use. A range of plant extract (yield 23.61%) concentration was prepared by diluting the extract in dimethyl sulfoxide.
In vitro screening of AGI activity of the fruits extract was carried out using the procedure by Iauk et al. Promising inhibitory activity was shown by nutmeg extract due to its comparable IC50 value (75.7 ± 2.3 μg/ml) to that of the positive control acarbose (35.5 ± 1.2 μg/ml). Other in vitro rat intestinal AGI activity by Patil et al. demonstrated that M. fragrans was responsible at inducing the insulin secretion in a dose-dependent manner. It was reported that nutmeg extract inhibited α-glucosidase enzyme at IC50 0.85 mg/ml, whereas acarbose recorded an IC50 0.031 mg/ml.
| Cosmos caudatus (Asteraceae)|| |
C. caudatus is locally known as Ulam Raja or “King's Salad” in Malaysia. It is originally grown in Latin America and later distributed extensively to Southeast Asia, especially Malaysia, Indonesia, and Thailand. Conventionally, the plant leaves are consumed as a booster for blood circulation, strengthening the bones, cooling effect for body, antiaging agent, and also beneficial in treating infectious diseases.
Javadi et al. had reported the inhibitory activity of C. caudatus leaves extract against α-glucosidase enzyme. A total of 108 samples of C. caudatus leaves were prepared, which was comprised of 18 replicates for each of the six different ethanol concentrations. Each sample that weighed 5.5 g was subjected to sonication for 30 min by immersion in ethanol at various concentrations (0%, 20%, 40%, 60%, 80%, and 100%). In addition, it was determined that hexane extract of the plant showed remarkable activity at inhibiting the α-glucosidase enzyme by Loh andHadira.
In addition, a metabolomics study to analyze the correlation between the activity and the potential responsible metabolites was also carried out by Javadi et al. The result showed that four compounds were active at inhibiting the enzyme. The compounds identity was confirmed using GC-MS NIST08 database library and literature data. They are phenolic and organic acids; α-tocopherol, catechin, α-linolenic acid (9Z,12Z, 15Z)-octadeca-9,12-, 15-trienoic acid, and α-D-glucopyranoside.
Other than that, C. caudatus has also been studied in an in vivo study, conducted by Perumal et al. In that particular study, rats treated with C. caudatus extract demonstrated a significant decline in plasma blood glucose after 1 month of C. caudatus extract supplementation as opposed to that of control group.
| Orthosiphon stamineus (Lamiaceae)|| |
O. stamineus is one of various plants widely found in tropical countries, especially in Southeast Asian region – Malaysia, Thailand, and Indonesia. In Malaysia, it is locally known as Misai Kucing or Cat's Whiskers. It is extensively used to treat many diseases including urinary tract disease, DM, hypertension, rheumatism, tonsillitis, and menstrual disorders.
Previously, a study to determine the potential of O. stamineus leaves at inhibiting α-glucosidase enzyme was conducted. Before extraction, the dried leaves were made into powder by a milling machine. Maceration method was performed with 50% (v/v) ethanol used as solvent. The extracts obtained were filtered and concentrated using a rotary evaporator and later was subjected to freeze-drying process. 10.3% of dry powder was attained. After that, the 50% ethanolic extract of O. stamineus was fractionated into ethyl acetate, butanol, and water extracts. The ethyl acetate fraction with antihyperglycemic activity was separated via silica-gel column chromatography to give two subfractions: ESF-1 (nonactive) and ESF-2 (active). The ESF-2 was fraction was then subjected to silica gel chromatography for bioactive compound isolation. Isolated compound was subjected NMR study.
In vitro α-glucosidase inhibition study was done using modified method by Apostolidis et al. The results showed that each concentration of the 50% ethanol extract of O. stamineus (62.5, 31.25, 15.6, 7.8, 3.9, and 1.95 mg/ml) and sinensetin inhibited α-glucosidase. The percentage inhibition of the extract displayed a concentration-dependent reduction, with the highest inhibition percentage (81.4%) recorded by 62.5 mg/ml of extract concentration, and the lowest inhibition percentage (16.2%) was determined from 1.95 mg/ml. Besides, sinensetin revealed strong inhibition percentages (89%–32%) against α-glucosidase enzyme with concentration range of 2.5–0.31 mg/ml. However, 50% ethanolic extract of O. stamineus was determined to be the least potent at inhibiting the enzyme as opposed to that of acarbose and sinensetin. This was proved by IC50 values of the inhibitor compounds; sinensetin (IC50 0.66 ± 0.025 mg/ml), acarbose (IC50 1.93 ± 0.281 mg/ml), and 50% ethanolic extract of O. stamineus (IC50 4.63 ± 0.413 mg/ml). The IC50 of sinensetin was found to be significantly lower that acarbose and 50% ethanolic extract of O. stamineus (P < 0.01). The inhibitory activity of extract against the enzyme was presumably due to the presence of different compounds. In addition, a previous study by Kwon et al. showed that phenolics, flavonoids, and glycosides present in the extract and responsible as effective AGIs.
| Conclusion|| |
From this review, it has been shown that Malaysian plants have great and promising potential as pharmaceutical agent, particularly to be developed as antidiabetics through the inhibition of α-glucosidase enzyme. This natural approach is thought to be safer and more convenient compared to its synthetic version (e.g., acarbose and voglibose). Most studies reviewed in this paper demonstrated the in vitro tests of the AGI activity of the plants extract, which gives evidence and strong biochemical rationale of their potential. Therefore, the promising results shall be carried forward to in vivo test to further verify the activity. Besides, data generated from these studies further promote the traditional use of plants in medicine.
Financial support and sponsorship
We are grateful to Research Initiative Grant (RIGS15-099-0099) approved by the Research Management Centre, International Islamic University Malaysia, Kuantan.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.
Chiasson JL, Rabasa-Lhoret R. Prevention of type 2 diabetes: Insulin resistance and beta-cell function. Diabetes 2004;53 Suppl 3:S34-8.
van de Laar FA, Lucassen PL, Akkermans RP, van de Lisdonk EH, Rutten GE, van Weel C, et al.
Alpha-glucosidase inhibitors for patients with type 2 diabetes: Results from a Cochrane systematic review and meta-analysis. Diabetes Care 2005;28:154-63.
Kumar S, Narwal S, Kumar V, Prakash O. A-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacogn Rev 2011;5:19-29.
Pinto Mda S, Kwon YI, Apostolidis E, Lajolo FM, Genovese MI, Shetty K, et al.
Potential of Ginkgo biloba
L. leaves in the management of hyperglycemia and hypertension using in vitro
models. Bioresour Technol 2009;100:6599-609.
Kwon YI, Apostolidis E, Shetty K.In vitro
studies of eggplant (Solanum melongena
) phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension. Bioresour Technol 2008;99:2981-8.
Yoshikawa M, Murakami T, Yashiro K, Matsuda H. Kotalanol, a potent alpha-glucosidase inhibitor with thiosugar sulfonium sulfate structure, from antidiabetic ayurvedic medicine Salacia reticulata
. Chem Pharm Bull (Tokyo) 1998;46:1339-40.
Manaharan T, Palanisamy UD, Ming CH. Tropical plant extracts as potential antihyperglycemic agents. Molecules 2012;17:5915-23.
Agamuthu P. Challenges and Opportunities in Agro-Waste Management: An Asian Perspective. In: Inaugural Meeting ofFirst Regional 3R Forum in Asia, Tokyo; 2009.
Morton JF, Dawling CF. Fruits of Warm Climates. Miami Florida:Morton; 1987.
Talbott SM, Morton DA, Templeman JF. Mangosteen – Traditional and modern uses. J Australas Integr Med Assoc 2005;16:10-11.
Ryu HW, Cho JK, Curtis-Long MJ, Yuk HJ, Kim YS, Jung S, et al.
A-glucosidase inhibition and antihyperglycemic activity of prenylated xanthones from Garcinia mangostana
. Phytochemistry 2011;72:2148-54.
Kim JY, Lee JW, Kim YS, Lee Y, Ryu YB, Kim S, et al.
A novel competitive class of a-glucosidase inhibitors: (E)-1-phenyl-3-(4-styrylphenyl) urea derivatives. Chembiochem 2010;11:2125-31.
Ferreira SB, Sodero AC, Cardoso MF, Lima ES, Kaiser CR, Silva FP, et al.
Synthesis, biological activity, and molecular modeling studies of 1H-1,2,3-triazole derivatives of carbohydrates as alpha-glucosidases inhibitors. J Med Chem 2010;53:2364-75.
Menzel C. The lychee crop. In: Asia and the Pacific. Bangkok, Thailand: Food and Agriculture Organization of the United Nations; 2002.
Thitilertdecha N, Teerawutgulrag A, Kilburn JD, Rakariyatham N. Identification of major phenolic compounds from Nephelium lappaceum
L. and their antioxidant activities. Molecules 2010;15:1453-65.
Palanisamy UD, Ling LT, Manaharan T, Appleton D. Rapid isolation of geraniin from Nephelium lappaceum
rind waste and its anti-hyperglycemic activity. Food Chem 2011;127:21-7.
Soeng S, Evacuasiany E, Widowati W, Fauziah N. Antioxidant and hypoglycemic activities of extract and fractions of rambutan seeds (Nephelium Lappaceum
L.). Biomed Eng 2014;1:13-8.
Widowati W, Herlina T, Ratnawati H, Mozef T, Chandra R. Antioxidant and platelet aggregation inhibitor activities of black tea (Camellia Sinensis
L.) extract and fractions. Med Plants-Int J Phytomed Relat Ind; 2011;3:21.
Thomas TJ, Panikkar B, Subramoniam A, Nair MK, Panikkar KR. Antitumour property and toxicity of Barringtonia racemosa
Roxb seed extract in mice. J Ethnopharmacol 2002;82:223-7.
Tachibana Y, Kato A, Nishiyama Y, Ikemi M, Ohoka K, Kawanishi K, et al.
Mitogenic activities in African traditional herbal medicines (Part II). Phytomedicine 1996;2:335-9.
Khan S, Jabbar A, Hasan CM, Rashid MA. Antibacterial activity of Barringtonia racemosa
. Fitoterapia 2001;72:162-4.
Gowri PM, Tiwari AK, Ali AZ, Rao JM. Inhibition of alpha-glucosidase and amylase by bartogenic acid isolated from Barringtonia racemosa
Roxb. Seeds. Phytother Res 2007;21:796-9.
Sulaiman SF, Ooi KL. Antioxidant and a-glucosidase inhibitory activities of 40 tropical juices from Malaysia and identification of phenolics from the bioactive fruit juices of Barringtonia racemosa
and Phyllanthus acidus
. J Agric Food Chem 2014;62:9576-85.
Chakraborty R, Biplab D, Devanna N, Sen S. Antiinflammatory, antinociceptive and antioxidant activities of Phyllanthus acidus
L. extracts. Asian Pac J Trop Biomed 2012;2:S953-61.
Banik G, Bawari M, Choudhury MD, Choudhury S, Sharma.GD. Some anti-diabetic plants of Southern Assam. Assam Univ J Sci Technol 2010;5:114-9.
Devi S, Saraju S, Paul SB. An overview on Cicca acida
). Assam Univ J Sci Technol 2011;7:156-60.
Andel VT, Behari-Ramdas J, Havinga R, Groenendijk S. The medicinal plant trade in suriname. Ethnobot Res Appl 2007;5:351-72.
Jagessar RC, Gomes G. Selective antimicrobial properties of Phyllanthus acidus
leaf extract against Candida albicans
, Escherichia coli
and Staphylococcus aureus
using stokes disc diffusion, well diffusion, streak plate and a dilution method. Nat Sci 2008;6:1545-740.
Habib MR, Sayeed MA, Rahman MM, Hasan R, Saha A.In vitro
evaluation of cytotoxic, antibacterial, antioxidant and phytochemical screening of petroleum ether extract of Phyllanthus acidus.
Int J Pharma Sci Res 2011;2:875-81.
Lee CY, Peng WH, Cheng HY, Chen FN, Lai MT, Chiu TH, et al.
Hepatoprotective effect of phyllanthus in Taiwan on acute liver damage induced by carbon tetrachloride. Am J Chin Med 2006;34:471-82.
Chulabhorn M, Prawat H, Prachyawarakorn V, Ruchirawat S. Investigation of some bioactive Thai medicinal plants. Phytochem Rev 2002;1:287-97.
Sousa M, Ousingsawat J, Seitz R, Puntheeranurak S, Regalado A, Schmidt A, et al.
An extract from the medicinal plant Phyllanthus acidus
and its isolated compounds induce airway chloride secretion: A potential treatment for cystic fibrosis. Mol Pharmacol 2007;71:366-76.
Ooi KL, Muhammad TS, Tan ML, Sulaiman SF. Cytotoxic, apoptotic and anti-α-glucosidase activities of 3,4-di-O-caffeoyl quinic acid, an antioxidant isolated from the polyphenolic-rich extract of Elephantopus mollis
Kunth. J Ethnopharmacol 2011;135:685-95.
Hossain SJ, Tsujiyama I, Takasugi M, Islam MA, Biswas RS, et al
. Total phenolic content, antioxidative, anti-amylase, anti-glucosidase, and antihistamine release activities of Bangladeshi fruits. Food Sci Technol Res 2008;14:261-8.
Das S, Das S, Bratati D.In vitro
inhibition of key enzymes related to diabetes by the aqueous extracts of some fruits of West Bengal, India. Curr Nutr Food Sci 2012;8:19-24.
Jain NK, Singhai AK. Protective effects of Phyllanthus acidus
(L.) skeels leaf extracts on acetaminophen and thioacetamide induced hepatic injuries in Wistar rats. Asian Pac J Trop Med 2011;4:470-4.
Azalina A, Iqbal M. Antioxidant activity and phytochemical composition of Cynometra cauliflora
. J Exp Integr Med 2013;3:337.
Ado MA, Abas F, Mohammed AS, Ghazali HM. Anti-and pro-lipase activity of selected medicinal, herbal and aquatic plants, and structure elucidation of an anti-lipase compound. Molecules 2013;18:14651-69.
Saidan NH, Hamil MS, Memon AH, Abdelbari MM, Hamdan MR, Mohd KS, et al.
Selected metabolites profiling of orthosiphon stamineus benth leaves extracts combined with chemometrics analysis and correlation with biological activities. BMC Complement Altern Med 2015;15:350.
Ado MA, Abas F, Ismail IS, Ghazali HM, Shaari K. Chemical profile and antiacetylcholinesterase, antityrosinase, antioxidant and α-glucosidase inhibitory activity of Cynometra cauliflora
L. Leaves. J Sci Food Agric 2015;95:635-42.
Patil SB, Ghadyale VA, Taklikar SS, Kulkarni CR, Arvindekar AU. Insulin secretagogue, alpha-glucosidase and antioxidant activity of some selected spices in streptozotocin-induced diabetic rats. Plant Foods Hum Nutr 2011;66:85-90.
Iauk L, Acquaviva R, Mastrojeni S, Amodeo A, Pugliese M, Ragusa M, et al.
Antibacterial, antioxidant and hypoglycaemic effects of Thymus capitatus
(L.) hoffmanns. et link leaves' fractions. J Enzyme Inhib Med Chem 2015;30:360-5.
Gerard B, Salleh H, Shekar SC. Health and Beauty from the Rainforest : Malaysian Traditions of Ramuan. Singapore: Editions Didier Millet; 2009.
Javadi N, Abas F, Abd Hamid A, Simoh S, Shaari K, Ismail IS, et al.
GC-MS-based metabolite profiling of Cosmos caudatus
leaves possessing alpha-glucosidase inhibitory activity. J Food Sci 2014;79:C1130-6.
Loh SP, Hadira O.In vitro
inhibitory potential of selected Malaysian plants against key enzymes involved in hyperglycemia and hypertension. Malays J Nutr 2011;17:77-86.
Perumal V, Hamid AA, Ismail A, Saari K, Abas F, Ismail IS, et al
. Effect of Cosmos caudatus
Kunth leaves on the lipid profile of a hyperlipidemia-induced animal model. J Food Chem Nutr 2014;2:43-51.
Jaganath IB, Teik NL. Herbs: The Green Pharmacy of Malaysia. MARDI, Serdang, Malaysia, 2000.
Awale S, Tezuka Y, Banskota AH, Adnyana IK, Kadota S. Nitric oxide inhibitory isopimarane-type diterpenes from Orthosiphon stamineus
of Indonesia. J Nat Prod 2003;66:255-8.
Mohamed EA, Siddiqui MJ, Ang LF, Sadikun A, Chan SH, Tan SC, et al.
Potent a-glucosidase and a-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus
Benth as anti-diabetic mechanism. BMC Complement Altern Med 2012;12:176.
Yam MF, Lim V, Salman IM, Ameer OZ, Ang LF, Rosidah N, et al.
HPLC and anti-inflammatory studies of the flavonoid rich chloroform extract fraction of Orthosiphon stamineus
leaves. Molecules 2010;15:4452-66.
Apostolidis E, Kwon YI, Shetty K. Inhibitory potential of herb, fruit, and fungal-enriched cheese against key enzymes linked to type 2 diabetes and hypertension. Innov Food Sci Emerg Technol 2007;8:46-54.
Tadera K, Minami Y, Takamatsu K, Matsuoka T. Inhibition of alpha-glucosidase and alpha-amylase by flavonoids. J Nutr Sci Vitaminol (Tokyo) 2006;52:149-53.