Mustaffa, F. et al.

/ Journal of Pharmacy Research 2011,4(11),4217-4224

Review Article ISSN: 0974-6943

Available online through www.jpronline.info

Mustaffa, F. 1, Indurkar, J.*1, Ali, N.I.M. 1, Hanapi, A. 1 Shah, M. 1, Ismail, S.1 and Mansor, S.M. 1 1 Centre for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia.

A Review of Malaysian Medicinal Plants with Potential Antidiabetic Activity

Received on: 19-05-2011; Revised on: 08-06-2011; Accepted on:01-07-2011 ABSTRACT
Diabetes mellitus is a common disease through out the world and Malaysia is one of the victim and it is estimated to increase by 2.48 millions diabetics by 2030. Plants and plant products has played an important role in the treatment of diabetes as early as 1550 B.C. Moreover, during the past few years some of the new diabetic drugs isolated from plants have shown hypoglycemic activity with more efficacy than oral diabetic agents commonly used in clinical therapy. This review compiles an overview of certain Malaysian antidiabetic plants with their specific mode of action and phytoconstituents which have been widely reported in the literature. The profiles presented include information about the scientific name, family, the mechanism of hypoglycemic activity and the active agents. The plants described in this review (Aloe vera, Andrographis paniculata, Centella asiatica, Curcuma longa, Ficus deltoidea, Gynura procumbens, Morinda citrifolia, Orthosiphon stamineus) clearly demonstrated the importance of herbal plants in the treatment of diabetes. Keywords: Diabetes mellitus, hypoglycemic, antidiabetic plants INTRODUCTION Medicinal plants have always been considered as healthy source of life for all people due to its rich in therapeutic properties and being 100% natural [1]. Medicinal plants are widely used by majority of populations to cure various diseases and illness and have high economic impact on the world economy [2]. Pang et al. [3] have reported that traditional herbal medicine is considered as the art of healing. The plant extracts and their constituents plays major role in traditional medicines and therapies [4]. Based on the statistical analysis, approximately 119 pure compounds isolated from plants are being used as medicine throughout the world [5]. Malaysia is gifted with variety of herbal medicine and these medicinal plants serve as the primary healthcare for locals. Since time immemorial, patients with diabetes mellitus has been treated orally with a various Malaysian plant extracts. Some of the plants extract have been experimentally evaluated and the active constituents also been isolated. Diabetes mellitus encounter as a major global health problem, affecting nearly 15 million of world populations [6]. The number of diabetic patients worldwide has estimated to rise from 2.8% in 2000 to 4.4% in 2030 [7]. Malaysia today has become a diabetic capital with over 8.2% of diabetic patient [8]. Diabetes mellitus is defined as the endocrine disorder that attributes to disturbance in carbohydrate, fat and protein metabolism [9]. This leads to the hyperglycaemia that associated with hypertension, artherosclerosis, neuropathy, retinopathy, nephropathy and angiopathy [10,11]. In recent trend, the treatment of diabetes involves the use of synthetic drug such as biguanides, thiazolidinediones, sulphonylurea, meglinetedes and a-glucosidase inhibitor [12]. However, some of these antihyperglycemic agents lead to hypoglycemic coma and hepatorenal disturbances that may responsible for the safety issue of human health [13]. Therefore, people are cautious about synthethic antidiabetic agent and diverting towards the naturally occurring hypoglycemic sources. This article has an objective to collect scattered scientific data on the Malaysian herbs with significant antidiabetic properties and to provide present status of the plants which antidiabetic potential has been proven scientifically . We believe that the list of medicinal plants presented in this review is useful for researchers to further exploration for necessary development of antidiabetic drugs. PLANTS WITH ANTIDIABETIC POTENTIAL The information on the plants having antidiabetic properties was collected from books, journals and websites. The plants described in this review are 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 Aloe vera Andrographis paniculata Centella asiatica Curcuma longa Ficus deltoidea Gynura procumbens Morinda citrifolia Orthosiphon stamineus

1.0 Aloe vera L. Burm. f. Family: Liliaceae Synonyms: Aloe barbadensis Miller Aloe indica Royle Aloe perfoliata L. var. vera Aloe vulgaris Lam Aloe chinensis Bak Aloe elongata Murray Aloe officinalis Forsk Aloe vera L. var. littoralis Knig ex Bak Aloe vera L. var. chinensis Berger 1.1 Miscellaneous The name of Aloe vera derived from the Arabic word alloeh which mean bitter. It is also known as lily of the desert, the plant of immortality, and the medicine plant. It is believed to be effective to treat wound, stomach ailments, gastrointestinal problems, skin diseases, constipation and radiation injury [14]. Hence, A. vera has been used as popular folk medicine for general health problems and currently used in many industries such as cosmetics for skin care, nutraceuticals and pharmaceuticals [15]. Furthermore, it possessed anti-inflammatory and anti-ulcer activity [16,17]. Besides that, A. vera also showed antidiabetic and hypoglycemic properties [18,19]. 1.2 Vernacular names English, Aloe capensis, aloe curacao, aloe vera, aloes, alos, alos du Cape, alos froce, aloes vrai, alos vulgaire, alovis, Barbadoes aloe, Barbadoes aloes, Barbados aloe, Bergaalwyn, Bitteraalwyn, Cape aloe, chirukattali, Curacao aloe, Curacao aloes, Curacao alos; Indian, Echte Aloe, ghai kunwar, ghai kunwrar, gheekuar, ghikanvar, ghikuar, ghikumar, ghikumari, ghikwar, ghiu kumari, ghrita kumari, ghritakumari, grahakanya, gwar-patha, haang takhe, hlaba, Indian aloe, jadam, korphad, kumari, kumaro, kunvar pata, kunwar, Chinese, laloi, laluwe, lo-hoei, lo-hoi, lou-houey, lu wei, luchuy, manjikattali; Meditteranean, Mediterranean aloe, murr sbarr, musabar, rokai, sabbara, saber, sbila, sabilla, sabr, saibr, savila, savilla, semper vivum, shubiri, sibr, siang-tan, star cactus, tuna, umhlaba, waan haang charakhe, wan-hangchorakhe, yaa dam, yadam, zbila, zambila [20,21,22]. 1.3 Habitat A. vera L. species is native to the Arabian Peninsula [23,24], southern and eastern Africa, China, Gibraltar, the West India and the Mediterranean countries [25]. A. vera is commercially cultivated in Haiti, South Africa, Aruba, India, Bonaire, Venezuela and the United States of America [21,25,26].

*Corresponding author.
Indurkar, J Centre for Drug Research, Universiti Sains Malaysia, 11800 Penang, Malaysia Tel: +60 46532121 Fax: +60 46568669 E-mail:jindurkar@usm.my

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1.4 Used parts Leaves [15]. 1.5 Morphological characteristics This plant is a cactus-like plant with green, dagger-shaped leaves that are fleshy, spiny, marginated, tapering and filled with a clear viscous gel. A. vera gel can be obtain from the parenchymatous cells of the leaves [27]. 1.5.1 Leaves Succulent, almost sessile perennial herb with 3050 cm leaves long and 10 cm broad at the base. The leaves are pea-green in colour which is present in white spot when young [26]. 1.5.2 Flowers Flowers are bright yellow tubular with 2535 cm in length and arranged in a slender loose spike, stamens frequently project beyond the perianth tube [26]. 1.6 Phytochemicals present in the plant Anthracene glycosides [26], Barbaloin [28,29], aloe-emodin-anthrone 10-Cglucoside type, barbaloin (aloin) (1540%) [27,30], hydroxyaloin (about 3%) were found in the leaves of A. vera . Barbaloin is in fact a mixture of aloin A (10S) and B(10R), aloinoside A and B. Aloin A and B interconvert through the anthranol form as do aloinoside A and B [27]. 1.7 Pharmacological action Yagi et al. [31] reported that A. vera high molecular weight fraction (AHM) with <10 ppm of barbaloin exhibited a significant hypoglycemic effect. This fraction can lower the blood glucose and the triglycerides level which are often high in diabetic patients. After six weeks of the animal study there was significant decreased in blood glucose level was observed. As for the triglycerides level, significant decrease was observed only after 4 weeks of the treatment with the leaves extract. According to Misawaa et al. [32], the glucose intolerance was improved in A. vera derived phytosterols treatment groups after 28 days in the oral glucose tolerance test. The serum free fatty acid (FFA) and triglyceride (TG) levels were reduced in continuous administration of A. vera derived phytosterols. Besides that, the total weights of abdominal fat tissues in treated rats were significantly lower than the control rats. These findings suggested that hyperglycaemia can be improved by A. vera -derived phytosterols. Kim et al. [33] studied the effect of processed A. vera gel (PAG) in the diet induced non insulin dependent diabetes mellitus. Mice exhibiting above 180 mg/dl blood glucose level were selected for this study. After 8 weeks oral administration of A. vera gel, blood glucose concentrations reduced to a normal level in rat. In order to confirm the antidiabetic effects, the intraperitoneal glucose tolerance test was carried out. The results indicated that the blood glucose level was lowered along with the decrease in insulin resistance. According to Noor e t a l. [15], A. vera extract shows antidiabetic property and hypoglycemic activity, which brings the level of fasting plasma glucose (FPG) to normal in diabetic-induced rats. 2.0 Andrographis paniculata Family : Acanthaceae Synonyms: Justicia latebrosa Russ Justicia paniculata Burm. f. Justicia stricta Lam. ex Steud 2.1 Miscellanous Andrographis paniculata have been a part of Indian Ayurvedic, Chinese, Thai and Malay traditional medicine for centuries. A. paniculata has a long history of use in traditional forms of oriental medicine to treat digestive problems, flu and upper respiratory infections. The plant extracts exhibits antityphoid, antifungal, antibiotic, antimalarial, antithrombogenic, antiinflammatory, antisnake venom, and antipyretic activities [34]. In addition, the plant extract is used as an effective remedy for hypertension and immune enhancing [35]. It also widely used as hepatoprotective agent and in malaria treatment [36, 37]. Besides, it helps to relieve fever and support normal body cardiovascular function [38]. 2.2 Vernacular names Traditional Chinese Medicine, Chuan-xin-lian, Chunlianqialio, Yiqianxi, Sifang-liang, Zhanshejian; Traditional Indian Medicine, Kalmegh, Kiryato, Mahatikta, Bhunimba; Traditional Thai Medicine, Fah Tha Lai, Nam Rai Pangpond; Malaysia, Hempedu Bumi, Sambiloto; Japan, Senshinren [39,40]. 2.3 Habitat It grows abundantly in India, Sri Lanka, Pakistan, Java, Malaysia, Taiwan and Indonesia, China and Thailand [40]. 2.4 Used parts Leaves, stem and roots [41]. 2.5 Morphological characteristic A. paniculata grows up to 30-110 cm in moist shady place [42]. 2.5.1 Flowers The flowers are small in lax, spreading axillary and terminal racemes or panicles. White with rose-purple spots can be observed in the petal [42]. 2.5.2 Stem The stem of this plant are dark green in colour, 0.3-1.0 m in height, 2-6 mm in diameter, quadrangular with longitudinal furrows and wings on the angles of the younger parts, slightly enlarged at the nodes [42]. 2.5.3 Leaves The leaves are glabrous, up to 8.0 cm long and 2.5 cm broad, lanceolate and pinnate [42]. 2.5.4 Seeds Numerous, subquadrate and yellowish brown in colour seeds can be found from this plant [42]. 2.6 Phytochemicals present in the plants Andrographolide, neoandrographolide, 14-deoxy-11, 12 didehyroandro grapholide, 14- deoxyandrographolide, isoandrographolide, andrographosterin and stigmasterol were found in A. paniculata [43,44,45]. 2.7 Pharmacological action In previous studies, aqueous extract [46] ethanolic extract [35] of A. paniculata whole plant showed potent action of glucose lowering effect in tested diabetic animal models induced by streptozotocin. In another studies, the aerial part of ethanolic extract of A. paniculata possessed significant antidiabetic activity against streptozotocin induced diabetic rats [39]. Roa et al. [47] reported on the antidiabetic action of the A. paniculata root extract in alloxan induced diabetic rats. The chloroform fraction of root extract of A. paniculata was shown to exhibited dose-dependent antidiabetic activity on tested rats. The hypoglycemic activity of A. paniculata root extract was almost similar to the glibenclamide (an antidiabetic drug). This study also revealed that there is no significant increase in urinary secretion of protein, albumin and urea in A. paniculata treated rats. In contrast, significant increase of protein, albumin and urea were observed in alloxan induced diabetic rats. This indicates that A. paniculata that serves as antidiabetic agent, have wider range of pharmacological activity as a nephroprotective agent by inhibiting the induce of diabetic nephropathy [47]. Andrographolide, the bioactive constituents of A. paniculata has shown to acquire significant enhancement of glucose utilization by lowering plasma glucose level [40]. The studies highlighted that A. paniculata possess significant antihyperglycemic activity and effectively inhibited the incidence of nephropathy. 3.0 Centella asiatica Family: Mackinlayaceae Synonyms : Hydrocotyle asiatica L. Trisanthus cochinchinensis Lour. 3.1 Miscellaneous Centella asiatica is a aromatic smelling herb from the family of Mackinlayaceae. In folk medicine, this herb has been used widely to treat a wide range of illness. Some of the oral antifertility agents found to be produced from the crude extract of C. asiatica [48]. Some more activities possesses by C. asiatica extract are antitumor [49], anti-inflammantory [50], antioxidant [51], immunomodulating [52], antigenotoxic [53], and radioprotective [54]. Besides that, this herb has been used traditionally to enhance the healing of small wounds. Furthermore, this plant extract also been included in the Indian pharmacopoeia and has been recommended to treat some of the skin diseases including eczema, leprosy and psoriasis [55]. This plant extract also has been used for the treatment of burns, itching and insect bites. 3.2 Vernacular names Malaysia, Pegaga; Hindi, Bemgsag, Brahma-Manduki, Gotukola, Khulakhudi, Mandookaparni; Malayalam, Kodagam, Kodangal, Kutakm, Kutannal, Muthal, Muttil, Muyalchevi; Telugu, Bekaparnamu, Bokkudu, Saraswataku, Mandukbrahmmi, Saraswati plant; Marathi, Karinga, Karivana; Tripura, Thankuni, Thunimankuni; Assam, Manimuni; Bihar, Chokiora; Oriya, Thalkudi; Urdu, Brahmi; Sanskrit, Bhekaparni, Bheki, Brahmamanduki, Darduchhada, Divya, Mahaushadhi, Mandukaprnika, Manduki, Mutthil, Supriya, Tvasthi; Kanarese, Brahmisoppu, Urage, Vandelagaillikiwigidda, Vondelaga; Gujrati, Barmi, Moti Brahmi; Tamil, Babassa, Vallarai; Bengal, Thankuni, Tholkuri; Deccan, Vallarai; Meghalaya, Bat-maina; Sinhalese, Hingotukola; USA, Indian Pennywort, Marsh Pennywort; Hawaii, Pohe Kula; Cook Islands,

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Kapukapu; Fiji, Totodro; China, Fo-ti-tieng, Chi-hsueuh-tsao; Nepal, Ghod tapre; Tahiti, Tohetupou; Samoa, Tonga Tono [56]. 3.3 Habitat C. asiatica can be found in swampy area of India, especially as a weed crop fields and also any places throughout India with an altitude of 600 m [57]. It is also flourishes extensively in shady, marshy, damp and wet places such as paddy fields and river banks forming a dense green carpet. 3.4 Used parts Leaves [58]. 3.5 Morphological characteristics C. asiatica is a faintly aromatic, prostrate, stoloniferous, perennial and creeper herb. It can grows up to 15 cm (6 inches) [56]. 3.5.1 Stem Stem is glabrous, striated and rooting at the nodes [56]. 3.5.2 Leaves It is 1-3 from each node of stems with 2-6 cm long of petioled and 1.5-5 cm wide, simple, orbicular-reniform, sheathing leaf base, crenate margins and glabrous on both sides and slightly hairy [56]. 3.5.3 Flowers Flowers are in fascicled umbels where each umbel consisting of three to four white to purple or pink flowers. The flowering month is April until June [56]. 3.5.4 Fruits Fruits are borne throughout the growing season and approximately 2 inches long, oblong, globular in shape, strongly thickened pericarp and brown coloured [56]. 3.5.5 Seeds Seeds have pedulous embryo which are laterally compressed [56]. 3.6 Phytochemicals present in the plant Triterpenoids, including asiatcoside, madecossoside, centelloside, thankuniside, isothankunic acid, centellose, asiatic, centellic and madecassic [59,60], glycerides of palmitic, stearic, lignoceric, oleic, linoleic and linolenic acids [61], alkaloid, hydrocotylin [61], flavanoids, 3-glucosylquercetin, 3glucosylkaemferol and 7-glucosylkaemferol have been isolated from the leaves [62]. C. asiatica leaves also produce an essential oil and flavonoid glycoside, hyperin [63,64]. 3.7 Pharmacological action Chauhan et al. [58] reported that C. asiatica leaves possess significant antidiabetic activity. Both ethanolic and methanolic extracts of C. asiatica leaves were tested for glucose tolerance test on normal rats as well as in alloxan induced diabetic rats for antidiabetic activity. Both ethanolic and methanolic extracts significantly lowered the blood glucose level to normal in glucose tolerance test. While the observation after 3 hours at dose level of 250 mg/kg of body weight in alloxan induced diabetic rats showed the maximum reduction in blood glucose. The ethanolic and methanolic extracts showed the percentage protections of 48% and 30% respectively. The degree of protection was determined by measuring blood glucose, triglycerides, cholesterol and urea on 0, 3, 5, 7 and 10th day for the long term treatment of alloxan induced diabetic rats. It can be concluded that both methanolic and ethanolic extracts showed a significant antidiabetic activity which is comparable to the glibenclamide (an antidiabetic drug). Sashida and Mimaki [65] examined the effect of C. asiatica extract and asiaticoside, the active component of C. asiatica for the hyperglycemia and hypertension. The results showed that C. asiatica and asiaticoside administrated group exhibited the significant effect in lowering blood glucose level after 14 days of administration. 4.0 Curcuma longa Family: Zingiberaceae Synonyms: Curcuma longa L. Curcuma aromatica Salisbury Curcuma domestica Valeton Curcuma dornestica Rumph 4.1 Miscellaneous Curcuma longa belongs to the family Zingiberaceae [66]. It is extensively used by the Indian, Persian, Thai and Malay population as an important dietary spice and as part of the local pharmacopoeia for treatment of known and emerging diseases ranging from bileary disorder and anorexia. Besides that, it is reported that C. longa possess antiinflammatory, anticancer, antiHIV and antimicrobial properties [67,68]. It is also stated that this plant has been used as coloring agent, medication and also as a magical symbol during ancient time [69,70]. Roth and team [71] reported that hexane extract of the leaves shows potential antifungal activity by inhibiting the growth of Candida albicans and exhibited mosquitocidal activities on Aedes aegyptii larvae. It is also reported that the leaf showed antioxidant properties and is proposed to be considered as alternative to the existing synthetic antioxidants in the market [72]. 4.2 Vernacular names Malaysia, Kunyit; India, Haldi, Kurkum, Manjano, Haldee, Huldee, Huldie; China, Iyu-chin, Wong geung fun; French, Saffron des indes; Africa, Borrie; Indonesia, kunjit, kunyit [73,74,75]. 4.3 Habitat C. longa can be cultivated all over India [69] and widely grown in Nigeria [76]. Besides that, it can also be found in tropical and subtropical country [77]. 4.4 Used parts Rhizome [78]. 4.5 Morphological characteristics This short branched and short stem plant measures up to 1 m in height and contain tufted leave [79]. The rhizome is decribed to be ovate, oblong, cylindrical and frequently found as short-branched [80]. The rhizome is said to produce pungent smell and bitter in taste. 4.5.1Leaves There are usually up to 10 leaves per C. longa Linn stem with simple, large and long characteristics [81]. This monocotyledon plant has parallel venation leaf [82]. Tumeric leaves are added during cooking preparation of meat and fish to introduce additional flavor to the dishes. These dishes are often serve with rice in South East Asia and are believe to posses medical values [72]. 4.5.2 Flowers The flowers of tumeric are pale yellow in colour. Ismail and team [81] stated that the flowers are arranged in spike where it grows on an upright stem and the bracts can be observed as pale green in color. 4.5.3 Raw juice With the daily consumption of 20 drops of raw turmeric ( C. longa) juice with salt in the morning, is said to be effective to expel worms. The mixture of this juice with honey is also used to treat anemia [83], since curcumin, the major constituents of tumeric possess iron-binding properties [84]. Dairam and group [84] also reported the possible effect of this compound in the neurodegenerative disease such as alzhemier. 4.5.4Tumeric Powder The yellow powder derived from the fresh rhizome by boiling and dried in hot air oven for 6 hours [85] or by sun dried for 10 days [86] followed by grinding procedure. The powder is a major coloring component of curry powder use for cooking and is used extensively as food coloring agent in food industry. 4.6Phytochemicals present in the plant The major constituent of this plant known as curcumoids is derived from the rhizome and the major coloring pigments that contributed to the yellow color of the plant is known as curcumin [87]. Curcumin (1,7-bis (4-hydroxy-3methoxyphenyl)-1,6-heptadiene-3,5-dione) is a polyphenolic diketone and being widely applied in the treatment of serious ailments [88]. Likewise, tumerin, a minor constituent of turmeric has also been reported to exhibit antioxidant activity [89]. The rhizome contain, demethoxycurcumin and bisdemethoxycurcumin [90]. Essential oil obtained from the leaf consist of phellandrene, 1,8-cineole, p-cymene, -pinene and terpinolene [91,92]. The essential oil of the rhizome contain ar-turmerone, tumerone and turmerol [93]. As for the essential oil of the roots comprise of ar-turmerone, arcurcumene and dehydro-curcumene [92]. 4.7 Pharmacological action 8 weeks of study on streptozotocin induced diabetic rats fed with the aqueous extract of C. longa has shown protective effect against type 2 diabetes mellitus, thus exert significant reduction in blood glucose level [94]. Likewise, Mohankumar et al. [95] discussed about the effect of aqueous extracts on pancrease and peripheral tissue that involve in the control of blood glucose level. The blood plasma level regulates insulin secretion in pancreatic beta cells and influences the uptake of glucose from the muscle tissue. The incubation of the extract with pancreases tissues showed stimulation on insulin secretion. The results of this study suggest the mimic of insulin action on

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peripheral tissue where the percentage of glucose uptake is also increase [95]. The alloxan induced rabbits expressed significant decrease in the plasma glucose level after the administration of the methanolic extract of C. longa for 12 consecutive days. Nwozo also have demonstrated the significant reduction of cholestrol level that often associates with diabetes mellitus on the turmeric treated rabbit [96]. Curcuminoids and sesquiterpenoids are the major components found in the ethanolic extract and exert stronger hypoglycemic effect than acting individually. The separate action of hexane extract which contained sesquiterpenoids and hexane residue (contained curcuminoids) denoted the antihyperglycemic activity of each of the compound when the results proved the suppression of blood glucose level of the type 2 diabetic in mice [97]. 5.0 Ficus deltoidea Family : Moraceae Synonyms : Ficus deltoidea Jack Ficus diversifolia Blume Ficus deltoidea var angustifolia sp. 5.1 Miscellaneous The genus Ficus is made up of about 1,000 species ranging from tropical and subtropical origins [98]. Plants in this genus are all woody plants include trees and shrubs [99]. F. deltoidea is the only Ficus species that produce fruits when cultivated indoors. It is used as traditional herbs and for ornamental purposes [100]. It also serves as a nice shrub or foreground subject for larger trees [101]. According to Malaysian natives, F. deltoidea is usually used by the women that have just give birth to regain energy, repair blood flows and womb contraction. Besides, F. deltoidea is used for reducing nerves and joints pain, headache, fever, pneumonia, diarrhea, gout, improving migraine condition, reducing cholesterol and blood lipids, improving blood circulation, delaying menopause and as toxin removing agent. In addition to its well know effect of increasing libido energy, it also has wider range of biological activities to treat skin related ailments such as eczema and blistered skin. This plant has also been traditionally claimed to have antidiabetic properties and was used as remedy for diabetes treatment [102,103]. The antinociceptive activity of aqueous extract of F. deltoidea has also been reported [104]. Recent study on enzymatic and non enzymatic antioxidant activities of F. deltoidea has also been reported [105]. 5.2 Vernacular names Malaysia, Mas Cotek, Serapat, Sempit-sempit, Angoluran; Indonesia, Tabat Barito, Ara Jelatih, Ara Tungal, Api-api Gajah, Andapai-apai, Telinga Kera; Africa, Kangkalibang [106]. 5.3Habitat Philippines, Malaysia, Hawaii, Africa and Indonesia [101]. 5.4 Used parts Stem, leaves, root, fruits [103,105]. 5.5 Morphological characteristic It is an evergreen shrub or small tree that is usually bushy [106]. 5.5.1Stems Either no swollen or very slight swollen [107]. 5.5.2 Leaves The scientific name, deltoidea or triangularis, refers to the shape of the leaf. The leaf shape is elliptical, lanceolate, obovate or spatulate. Only the spatulate-shaped leaf form is regularly sold and cultivated. The leaves are 3-inchlong, thick, leathery and dark green in colour [107]. The major difference between the male and female F. deltoidea is the leaves structure. The male plant has small, long and thin leaves. There are also red spots at the back of the leaves of the male plant. For the female F. deltoidea, the leaves are bigger and thicker. In contrast to male plant, the color of spots at the back of its leaves is black. Other than that, the leaves lines can be seen more clearly on the surface of the female leaves compared to males leaves [106]. 5.5.3 Branches The common name, mistletoe fig, comes from the habit of the plant as an epiphyte that grows on larger trees to reach for sunlight source. This plant grows up to 20 feet tall. It is a spreading shrub with slender zigzagging branches [101]. 5.5.4Root Aerial type of roots [101]. 5.5.5 Fruit This plant has sweet, fleshy, oval to round in shape fruit [101]. 5.5.6 Seed Seeds are minute [101]. 5.5.7Bark The bark is grey, slender and usually leaning. The twigs are reddish hairy and have persistent stipules [101]. 5.6Phytochemicals found in the plant Flavonoids [108], a-tacopherol [109], steroid, triterpenoids [110], alkaloid, phenol, proanthocyanin, tannin, naringin were found in F.deltoidea plant [111]. 5.7 Pharmacological action This plant is one of the commonly used medicinal plants as antidiabetic agent for diabetes treatment in Malaysia [103]. Study on the antidiabetic mechanism of F. deltoidea done by Aminuddin et al. [112] on normal and diabetic rats has revealed that this plant act as hypoglycemic agent. In another studies carried out by Adam et al. [103], the effect of F. deltoidea on insulinstimulated glucose uptake was assessed by using Chang liver cells as the model of hepatocytes cells. This investigation revealed that extracts (hot aqueous, cold aqueous, ethanolic and methanolic) and fractions (acidified chloroform and bacified chloroform) of F. deltoidea enhanced basal glucose uptake by Chang liver cells line. This glucose uptake was relatively higher than 100 nM insulin. This suggests that extracts and fractions of F. deltoidea stimulate glucose uptake by insulin mimetic activity. The mechanism of insulin mimetic activity of F. deltoidea might be through the induction of tyrosine phosphorylation of insulin receptor, insulin receptor substrate 1 (IRS1) and p85 subunit of phosphotidylinositol-3-kinase (PI3K), hence lead to adipocytes and liver cells uptake of glucose [12]. Interestingly, methanolic extract and nbutanolic fraction of F. deltoidea enhance insulin-stimulated glucose uptake significantly higher than 100nM insulin alone. This indicates that extracts and fraction of F. deltoidea exhibit insulin sensitizing activity [113]. The insulin sensitizing activity of F. deltoidea might act as IR (insulin receptor) activator by stimulating tyrosine phosphorylation activity and activation of downstream kinases activity [114]. The methanolic extract showed insulin sensitizing activity on Chang liver cells as good as rosiglitazona maleate (an antidiabetic drug) [103]. The insulin mimetic and insulin sensitizing activity of F. deltoidea suggest that antidiabetic compound present in this plant enhance the glucose disposal into liver [103]. Some antidiabetic plant showed synergistic effect with insulin for their antidiabetic properties [115]. However, there is no synergistic effect was found between F. deltoidea and 100 nM insulin on glucose uptake into Chang liver cell line [103]. The insulin mimetic and sensitizing activity possessed by F. deltoidea may due to the presence of flavonoid and tannins [116]. 6.0 Gynura procumbens (Lour.) Merr. Family : Compositae Synonyms : Gynura sarmentosa , DC,Cacalia procumbens Lour,Calacia procumbens Lour 6.1 Miscellaneous Gynura procumbens belongs to family Compositae. The leaves of this plant are edible as ulam and flavouring for food. G. procumbens has been reported to medicate kidney problem, fever and rashes [117]. In Thailand, the aerial part of this plant has been used traditionally for the treatment of inflammation, rheumatism and viral infection of the skin. In Indonesia, it has been used to treat fevers, skin rashes and as tonic to treat ringworm infection. G. procumbens leaves extract has been reported to exhibit hypotensive and antiinflammatory activity [118,119]. Other species of Gynura has also been reported for their medicinal properties such as G. divaricata which helps to combat craving for opium addiction and G. formosana possess antihemorrhagic activity [120,121]. In Malaysia, G. procumbens is used as folk medicine to treat diabetic patients. 6.2 Vernacular names G. procumbens ( Lour.) Merr. is locally known as sambung nyawa, kecam akar, akar sebiak or daun dewa. It also known as bai bing cha by the chinese in Malaysia [122]. 6.3 Habitat The species originated in Africa and was traded widely to China before it arrived to South East Asia, Australia and Sri Langka [123]. 6.4 Used part Leaves [124]. 6.5 Morphological characteristics This herbaceous medicinal plant grows approximately around 10 to 25 cm tall [125].

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6.5.1 Leaves The leaves are fleshy, hairy on both surfaces and vary in shape either ovate or oblong-elliptic, with rounded or cuneate base and an obtuse or acute, oftenattenuated apex [126]. 6.6 Phytochemicals reported in this plant Phytochemical studies of ethanol and water extract of leaves G. procumbens has led to the isolation of flavonol and flavonol glycosides. Further studies on butanol fraction of methanol extract of leaves G. procumbens revealed five compounds namely quercetin, kaempferol 3-O-glucoside, quercetin 3-Oramnosil (1?6) glucoside, quercetin 3-O-ramnosil (1?6) galactoside, and kaempferol 3-O-ramnosil (1?6) glucoside [127]. Kaempferol 3-O-rutinoside and astralagin were isolated from water extract of leaves G. procumbens [128]. 6.7 Pharmacological action There are several scientific reports that had proven the antidiabetic properties of G. procumbens. Zhang and Tan [129] have reported that ethanolic extract of G. procumbens leaves has antihyperglycemic activities in diabetic rats. In their studies, the antidiabetic activity was evaluated in the normal and streptozotocin (STZ) induced diabetic rats. The ethanolic extract acts peripherally by reducing plasma glucose level via absorption through muscle, adipocyte or hepatocyte cells. Three doses of G. procumbens (50, 150 and 300 mg/kg) were administered into the rats and the optimum hypoglycemic dose was found to be 150 mg/kg. Rasadah et al. [119] reported that methanol extract and n-buthanol fraction of G. procumbens leaves at dose 1g/kg possessed antihyperglycemic activity and stimulated insulin release in insulingsecreting cells. In addition, there was no cytotoxic effect has been observed at the effective dose. The aqueous extract of G. procumbens significantly reduced blood glucose levels after 14 days of treatment and improved the outcome of the intraperitoneal glucose tolerance test (IPGTT). For the in vivo and in vitro RIN-5F cell culture test, aqueous G. procumbens extract did not showed any significant effect on insulin level. In addition, the extract showed least effect on -cells of the islets of Langerhans in the pancreas. Furthermore, G. procumbens proved significant increased of glucose uptake by muscle tissues. It can be concluded that aqueous extract of G. procumbens exerted its hypoglycemic effect by promoting glucose uptake by the muscle [128]. 7.0 Morinda citrifolia L Family: Rubiaceae Synonym : None 7.1Miscellaneous Morinda citrifolia is from the family of Rubiaceae. The genus of Morinda made up of 80 species which grow in tropical climate zones. This plant has a long tradition as a medicinal plant in India and Pacific Islands. Traditionally, M. citrifolia has been used for its antibacterial, antiviral, antifungal, antitumor, anti-helmin, analgesic, hypotensive, anti-inflammatory activity and immune enhancers effects fruit and seed were blended together and the juice extract used as a remedy for diabetes [130]. 7.2Vernacular names India, Great morinda, Nunaakai, Indian mulberry ; Barbados, dog dumpling; Indonesia, Mengkudu, Kumudu, Pace; Malaysia, Mengkudu, Ba Ji Tian ; Hawaian, Beach mulberry, Cheese fruit, Noni [131,132,133]. 7.3 Habitat It can be found throughout Pacific Islands Polynesia, Asia, and Australia [132] 7.4 Used part Leaves, fruits, roots, stems, bark, flowers [134]. 7.5 Morphological characteristics M. citrifolia is an evergreen tree or shrub with the height of 3 to 6 m. Sapwood is yellow-brown and soft [131]. 7.5.1 Leaves Leaves maybe rounded, elliptic or long and strap-like. The rounded leaves are 15-30 cm wide and 20-40 cm long. For the strap-like leaves it can be 10 cm wide and 60 cm long [135]. 7.5.2 Fruits The fruit is ovoid shape with warty pitted surface. The young fruit is hard and has a bright green in color. When mature, the fruits become very soft, soupy smell and have foul taste [136]. 7.6 Phythohemical composition of the plant 7.7 2-methyl-4-hydroxy-5,7-dimethoxyanthraquinone 4 - O- -dglucopyranosyl-(1g4)--1-rhamnopyranoside, 5,8-dimethyl-apigenin 4'-O-d-galactopyranoside, Aracetin 7-O--d-glucopyranoside were found in the flower part of M. citrifolia [137]. -d-glucopyranose pentaacetate, 2,6-di-O(-d-glucopyranosyl-1-O-octanoyl--d-glucopyranose, 6-O-(-d-glucopyrano syl-1-O-octanoyl--d-glucopyranose, Ascorbic acid, Asperulosidic acid, Asperuloside tetraacetate, Caproic acid, Caprylic acid, Ethyl caprylate, Ethyl caproate, Hexanoic acid, Octanoic acid, Quercetin 3-O-a-l-rhamnopyranosyl(1g6)--d-glucopyranoside were found in the fruits of M. citrifolia (133,137, 138,139,140,141]. Leaves of M. citrifolia contain Amino acids, -sitosterol, Citrifolinoside B, Kaempferol 3-O-a-l-rhamnopyranosyl-(1g6)--d-glucopy ranoside, Kaempferol 3-O--d-glucopyranosyl-(1?2)-a-l-rhamnopyranosyl(1g6)--d-galactopyranoside, Quercetin 3-O--d-glucopyranoside, Quercetin 3- O- -d-glucopyranosyl-(1g 2)- - l - r h a m n o p y r a n o s y l - ( 1 g 6)- -dgalactopyranoside, Ursolic acid [137,138,139,142,143]. In the root part of M. citrifolia, Morindone, Damnacanthal, 8-hydroxy-8-methoxy-2-methylanthraquinone, rubichloric acid, 1,3-dihydroxy-6-methyl Anthraquinone, Morenone 1, Morenone 2, Ruberythric acid, Rubiadin, Chlororubin, Hexose, Morindadiol, Morindanidrine, Morindine, Pentose, Physcion, Rubiadin monomethyl ether, Soranjidio, Trioxymethylanthraquinone monoethyl ether and Alizarin were found[132,135,137,138,139,141,142,143]. 7.8 Pharmacological action According to Rao and Subramaniam [144], oral treatment of fruits extract of M. citrifolia as well as glyclazide (an antidiabetic drug) lowered the level of blood glucose and improved the insulin level in streptozotocin (STZ) induced diabetic rats. The antidiabetic effect of M. citrifolia might due to the stimulatory effect on the remnant -cells to secrete more insulin. In addition, Kamiya et al.[145] also reported that the root extract of M. citrifolia has antidiabetic property. Horsfal et al. [146] has reported that M. citrifolia fruit juice has blood glucose lowering activity. In their study, Tahitan Noni juice was used for the treatment and it showed that the juice had the best glycaemic control as compared to other group. Besides, fermented juice of M. citrifolia also showed positive result in controlling blood sugar [147]. The presence of flavonoids, triterpenoid, triterpenes and saponin in M. citrifolia could be involved in lowering of the blood glucose. It has been reported that saponin stimulates insulin release from the pancreas [148]. This can be related to the decreased glucagon level. On the other hand, flavonoids such as rutin that was found in the noni fruit may act as secretagogue, which potentiates insulin secretion by a mechanism related to that of sugar sucrose. 8.0 Orthosiphon stamineus Family: Lamiaceae Synonyms : Orthosiphon stamineus Benth,Ocimum aristatum BI,Orthosiphon aristatus (Blume). 8.1 Miscellaneous The genus name Orthosiphon stamineus was derived from two Latin words, siphon and iorthos. The word siphon referred to cylindirical or tube like whereas iorthos meant straight. Both of these words actually indicate the straight tube like flowers present in the Orthosiphon species. The flowers served as the unique characteristic of Lamiaceae family [117]. This plant is used for treating the ailments of the kidney, since it has a mild diuretic effect. Besides, O. stamineus had been used traditionally for the treatment of renal stones, nephritis, gout, diabetes, hypertension and rheumatism. The plant extracts exhibited anti-fungal, anti-bacterial, anti-allergenic, anti-hypertensive and anti-inflammatory activities [149]. 8.2 Vernacular names Malaysia, Misai Kucing; Indonesia, Kumis Kucing, Remujung ; Thailand, Yaa Nuat Maeo, Rau Meo or Cay Bac; French, moustaches de chat ; European; Java Tea [150]. 8.3 Habitat O. stamineus is found in Malaysia, Thailand, Indonesia and Europe [151]. 8.4 Used parts Leaves [152]. 8.5 Morphological characteristic It is an herbaceous shrub which grows to a height of 1.5 meters tall [150]. 8.5.1 Flowers The flowers are borne on vertical about 16 cm length, white to bluish in colour with long far-exerted filaments, making it look like cats whiskers [153]. 8.5.2 Leaves The leaves of O. stamineus are arranged in opposite pairs. The petiole is

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relatively short, about 0.3 cm in length and reddish purple in colour [153]. 8.5.3 Stem The stem is square shaped and green in colour [154]. 8.5.4 Root O. stamineus produced well developed fibrous root system [154]. 8.5.5 Seeds The seeds is oval in shape with hard and rough surface testa [154]. 8.5.6 Fruit The fruit is in purple or greenish red in colour [154]. 8.6 Phytochemicals present in the plant Rosmarinic acid, caffeic acid, cirrchoric, sinensetin and eupatorin were present in the leaves of O. stamineus [155]. 8.7 Pharmacological action In previous studies, aqueous extract of O. stamineus leaves showed potent action of glucose lowering effect in both normal and diabetic animal model induced by streptozotocin. The effect of daily administration of O. stamineus on insulin secretion was also examined using the pancreatic perfusion technique. This study provided the information regarding stimulatory effect of the O. stamineus extract on insulin secretion from the pancreatic beta cells. In addition, O. stamineus also showed significant decrease in triglyceride level and increased plasma high density lipoprotein-cholesterol concentrations [152]. These results suggest that O. stamineus extract have protective effects against hyperlipidemia and hypertriglyceride which are the most common lipid abnormalities in diabetes patient [156,157]. In addition, increase in plasma and triglyceride concentrations may enhance the development of diabetes complications such as neuropathy, nephropathy, cardiovascular and cerebrovascular diseases [158]. This clearly indicates that O. stamineus may be consumed as natural remedies by the diabetic patients for the protection against hyperlipidemia and hypertriglyceride. CONCLUSION This article provided a list of various Malaysian plants used in the treatment of diabetes mellitus. Scientific validation of several Malaysian plant species has clearly demonstrated the efficacy of the botanicals in reducing the sugar level. Keeping in view from the reports on their potential effect against diabetes, it is assumed that the botanicals have major role to play in the management of diabetes, by delaying the development of diabetic complications and correcting the metabolic abnormalities. REFERENCES
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Journal of Pharmacy Research Vol.4.Issue 11.November 2011

4217-4224