IJPCBS 2013, 3(3), 983-992 Saravanan K et al. ISSN: 2249-9504

INTERNATIONAL JOURNAL OF PHARMACEUTICAL, CHEMICAL AND BIOLOGICAL SCIENCES

Available online at www.ijpcbs.com Research Article

A SYSTEMATIC REVIEW ON MEDICINAL USED TO TREAT DIABETES MELLITUS S. Elavarasi, K. Saravanan* and C. Renuka PG & Research Department of zoology, Nehrzu Memorial College (autonomous), Puthanampatti – 621 007, Tiruchirappalli, Tamil Nadu, .

ABSTRACT Diabetes mellitus (DM), both insulin-dependent DM (IDDM) and non-insulin dependent DM (NIDDM) is a common and serious metabolic disorder throughout the world. Several oral hypoglycemic agents and insulin therapy are the primary forms of treatment for diabetes. However, prominent side effects of such drugs are the main reason for an increasing number of people seeking alternative therapies that may have less severe or no side effects. Several medicinal plants have been used to control diabetes in the traditional medicinal systems of many cultures worldwide. Many more medicinal plants have found potential use as hypoglycemic in the Indian system of medicines. In this review, there are 39 plants described. It clearly shows the importance of herbal plants in the treatment of diabetes mellitus. The present review profile-gives information about scientific name, common name, family and the parts of the used to treat diabetes.

Keywords: Diabetes mellitus, Medicinal plants.

INTRODUCTION hypoglycemic properties and other beneficial Diabetes mellitus is a syndrome of disordered properties, as reported in scientific literatures2. metabolism, usually due to a combination of This review clearly shows the importance of hereditary and environmental causes, resulting herbal plants in the treatment of diabetes in hyperglycemia due to defects in either insulin mellitus. secretion or insulin action in the body. Chronic hyperglycaemia during diabetes causes Indian Medicinal Plants to Treat Diabetes glycation of body proteins that in turn lead to Mellitus secondary complications affecting eyes, kidneys, India has an officially recorded list of 45,000 nerves and arteries1. plant species and a various estimation of 7500 The treatments of diabetes include diet, species of medicinal importance3. India has a exercise, use of oral hypoglycemic agents and rich history of using various potent herbs and insulin is the primary forms of treatment for herbal components for treating diabetes. Many diabetes. Currently available synthetic Indian plants have been investigated for their antidiabetic agents besides being expensive beneficial use in different types of diabetes and produce serious side effects. Apart from reported in numerous scientific journals. In this currently available therapeutic options, many review, there are 39 plants belonging to 30 herbal medicines have been recommended for families described about their uses in curing the treatment of diabetes mellitus, medicinal diabetes. The table 1 shows the information plants have the advantage of having no side about scientific name, common name, family and effects1. Traditional plant treatments have been the parts of the plant used to treat diabetes and used throughout the world for the therapy of the table 2 shows the pictures of the medicinal diabetes mellitus. History showed that plants. medicinal plants have been used in traditional healing around the world for a long time to treat diabetes; this is because such herbal plants have 983 IJPCBS 2013, 3(3), 983-992 Saravanan K et al. ISSN: 2249-9504

Acorus calamus (ACORACEAE) [Fig.1] Ichnocarpus frutescens (APOCYNACEAE) Oral administration of methanolic extract of A. [Fig.7] calamus rhizome restored the levels of blood Oral administration of the polyphenolic extract glucose in Streptozotocin induced diabetic rats of I. frutescens (150 and 300 mg/kg bw) after 21 days. Further, lipid profile (total significantly reduced the fasting blood glucose cholesterol, LDL and HDL-cholesterol), glucose levels, hepatic HMG-CoA reductase activity 6-phosphatase, fructose 1,6 bis phosphatase decreased the total cholesterol, triglyceride, levels and hepatic markers enzymes (aspartate VLDL, HDL and LDL level in alloxan diabetic aminotransferase, alanine aminotransferase, rats10. alkaline phosphatase) were decreased 4. Acanthopanax senticosus (ARALIACEAE) Sclerocarya birrea (ANACARDIACEAE) [Fig.2] [Fig.8] The methylene chloride/methanol extract (150 A hot water extract (85-95°C) of A. senticosus and 300 mg/kg bw) of S. birrea stem stem bark significantly decreased the plasma significantly reduced the blood glucose level, glucose level without affecting plasma insulin plasma cholesterol, triglyceride and urea levels levels and inhibited α-glucosidase activity in to the normal level and increased plasma insulin diabetic mice. The addition of A. senticosus level in STZ induced diabetic rats5. extract inhibited α-glucosidase activity but not α-amylase activity. Thus it would be useful as Annona squamosa (ANNONACEAE) [Fig.3] an ingredient of functional foods to improve Aqueous extract of A. squamosa (at a dose postprandial hyperglycemia and prevent type II of 250 mg/kg and 500 mg/kg bw) when given to diabetes mellitus11. STZ- induced diabetic rats reduced the blood Caralluma sinaica (ASCLEPIADACEAE) [Fig.9] glucose level from 285.52 to 208.81 mg/dl, 6 Treatment with alcoholic extract of C. sinaica hours after oral administration of extract6. (200 mg/kg bw) and aerial parts significantly reduced blood glucose level in STZ Polyalthia longifolia (ANNONACEAE) induced diabetic rat12. [Fig.4] Oral administration of the methanolic extract of Terminalia bellerica (COMBRETACEAE) P. longifolia bark (200 and 300 mg/kg bw) [Fig.10] reduced the fasting blood glucose, moreover the The hexane (200mg/kg bw), ethylacetate elevated levels of SGOT, SGPT, ALP, triglycerides (300mg/kg bw) and methanol (300 mg/kg bw) and total cholesterol were restored to near crude extracts of T. bellerica significantly normal level in STZ induced diabetic rats7. reduced the blood glucose level, total cholesterol, triglycerides, LDL cholesterol level, Ferula asafoetida (APIACEAE) [Fig.5] urea, uric acid, creatinine and serum total The intraperitoneal injection of aqueous extract protein level while it increased the plasma of F. asafoetida resin decreased the blood insulin level of STZ induced diabetic rats13. glucose level and increased the insulin secretion in the alloxan-induced diabetic rat model. The Costus speciosus (COSTACEAE) [Fig.11] extract stimulated the changes of the functional Oral administration of Eremanthin (a compound state of pancreatic β-cells and had beneficial isolated from the plant C. speciosus rhizome) effect by partly preserved or restored pancreatic decreased the HbA1c, serum total cholesterol, β-cell mass8. triglyceride, LDL-cholesterol level and at the same time markedly increased plasma insulin, Catharanthus roseus (APOCYNACEAE) [Fig.6] tissue glycogen, HDL-cholesterol and serum The administration of C. roseus powder (100 protein of STZ induced diabetic rats. It also mg/kg bw) lowered the plasma glucose and restored the plasma enzyme levels to near increased the plasma insulin were observed normal. Thus it –possessed a significant after 15 days in STZ induced diabetic rats. The hypoclycemic and hypolipidemic activities and significant enhancement in plasma total hence it could be used as a drug for treating cholesterol, triglycerides, LDL and VLDL- diabetes14. cholesterol, and the atherogenic index of diabetic rats were normalized in extract treated Vaccinium bracteatum (ERICACEAE) [Fig.12] diabetic rats9. Intragastric administration of the aqueous and ethanolic extract of V. bracteatum leaves

984 IJPCBS 2013, 3(3), 983-992 Saravanan K et al. ISSN: 2249-9504 significantly ameliorated the body weight, blood that flavonoids, steroids/terpenoids, phenolic glucose, insulin and plasma lipid levels of STZ- acids are known to be bioactive antidiabetic induced diabetic mice15. The effect of V. principles24, 25. bracteatum aqueous extract on the diabetic mice Elavarasi et al26 reported that the flowers of C. was superior to that of V. bracteatum ethanolic auriculata are used as an important ingredient extract15. in the poly herbal diabetic drug formulations prepared by Tribals of Kolli Hills, Tamilnadu to Jatropha curcas (EUPHORBIACEAE) [Fig.13] treat the diabetes. Oral administration of ethanolic extract of J. curcas leaves (250 & 500 mg/kg bw) Ougeinia oojeinensis (FABACEAEA) [Fig.18] significantly decreased the blood glucose level The ethanolic extract of O. oojeinensis (200 and can therefore be used as an alternative mg/kg) bark significantly decreased the blood remedy for the treatment of diabetes mellitus glucose level, triglycerides, LDL, VLDL and total and its complications16. cholesterol and increased high density lipoprotein level in alloxan induced diabetic Securinega virosa (EUPHORBIACEAE) rats27. [Fig.14] Intraperitoneal administration of (100, 300 and Cinnamonum zeylanicum (LAURACEAE) 600 mg/kg bw) methanol extract from S. virosa [Fig.19] leaves significantly reduced the blood glucose A compound Cinnamaldehyde isolated from C. level of STZ induced diabetic rats17. zeylanicum bark. The oral administration of a Cinnamaldehyde compound (20 mg/kg) Emblica officinalis (EUPHORBIACEAE) significantly decreased the HbA1C, serum total [Fig.15] cholesterol, triglyceride levels and at the same Oral administration of ethanolic extract of seed time markedly increased plasma insulin, hepatic powder of E. officinalis decreased the blood glycogen and high density lipoprotein- glucose level and serum cholesterol level in cholesterol levels in STZ-induced diabetic rats28. alloxan induced diabetic rats18. It also restored the plasma enzyme reduction in blood glucose level26. Trigonella foenum-graecum (FABACEAEA) [Fig.16] Allium cepa (LILIACEAE) [Fig.20] Seeds of fenugreek have been shown to have Essential oil (100 mg/kg) obtained from the red multiple benefits in patients with diabetes such onion significantly decreased the blood glucose as reduction of blood glucose level and its level, serum lipids, lipid peroxide formation and complications18-21. Ethanolic extract of T. foenum serum nitric oxide level and increased the serum graecum seed significantly decreased the blood insulin level in STZ induced diabetic rats29. glucose, serum cholesterol, SGOT and SGPT levels of alloxan induced diabetic rats20-21. Strychonous potatorum (LOGANIACEAE) Neveen et al22 reported that alkaloid extract of [Fig.21] fenugreek dried seeds significantly increased Oral administration of the ethanolic extract of S. serum insulin level of STZ induced potatorum plant material significantly decreased hyperglycemic rats. the AST, ALT and ALP level along with reduction of blood glucose level of alloxan induced auriculata (FABACEAEA) [Fig.17] diabetic rats30. Oral administration of the ethanolic extract of S. auriculata (at a dose of 150 mg/kg of bw) leaf Adansonnia digitata (MALVACEAE) [Fig.22] significantly reduced the blood glucose level, Intraperitoneal administration of methanolic SGOT, SGPT, ALP, total cholesterol, triglyceride extract of A. digitata stem bark (100 mg/kg bw) and low density lipoprotein-cholesterol (LDL-C) significantly decreased the blood glucose level of levels to the normal level and significantly STZ-induced diabetic Wistar rats31. increased HDL-C and phospholipid (PL) level in alloxan induced diabetic rats23. S. auriculata leaf Hibiscus rosa sinensis (MALVACEAE) [Fig.23] gained much importance in diabetic control as it Treatment with the aqueous extract of H. rosa has been used as a traditional medicine for sinensis (500 mg kg-1) aerial part reduced the diabetes; since the phytochemical analysis has blood glucose level, urea, uric acid and shown the presence of potent phytochemicals creatinine but increased the activities of insulin, like flavonoids, terpenoids, glycosides, steroids, C-peptide, albumin, albumin/globulin ratio and saponin and phenols. Several authors reported restored all marker enzymes to near control

985 IJPCBS 2013, 3(3), 983-992 Saravanan K et al. ISSN: 2249-9504 levels of STZ-induced diabetic rats. Thus, it significantly reduced the blood glucose level of exhibited an antihyperglycaemic effect and alloxan induced diabetic rats40. consequently may alleviate liver and renal damage associated with STZ-induced diabetes mellitus in rats32. Rumex patientia (POLYGONACEAE) [Fig.31] An Ethnobotanical survey of Elavarasi et al26 Seed powder supplementation of R. patientia stated that the H. rosa sinensis flowers used for showed reduction in serum glucose level, LDL treatment of diabetes. cholesterol level and increased the HDL- cholesterol level of STZ induced diabetic rats41. Ficus benghalensis (MORACEAE) [Fig.24] The aqueous extract of F. bengalensis stem bark Posidonia oceanica (POSIDONIACEAE) significantly reduced the blood glucose level of [Fig.32] STZ induced diabetic rats33. The aqueous ethanolic extract of P. oceanica leaves (150 and 250 mg/kg bw) significantly Ficus Glomerata (MORACEAE) [Fig.25] decreased the blood glucose level, ALP, GSH, The ethanolic extract of F. Glomerata leaves SOD, GPx, CAT, GPT and nitric oxide level to the reduced the blood glucose, serum urea, normal level in alloxan induced diabetic rats42. creatinine and cholesterol level of alloxan induced diabetic rats34. Bruguiera gymnorrhiza (RHIZOPHORACEAE) [Fig.33] Ficus religiosa (MORACEAE) [Fig.26] Oral administration of ethanolic extract of B. Oral administration of aqueous extract of F. gymnorrhiza root (400 mg/kg b.wt) significantly religiosa bark significantly reduced the blood reduced the blood sugar level, total cholesterol, glucose level and increased the serum insulin triglycerides, VLDL and LDL and significantly level, glycogen content in liver and skeletal increased the HDL level of STZ induced diabetic muscle in STZ-induced diabetic rats35. rats43.

Psidium guajava (MYRTACEAE) [Fig.27] Aegle marmelos (RUTACEAE) [Fig.34] A hot water extract of P. guajava unripe The methanolic extract of leaf and callus peel (400 mg/kg) significantly decreased the powder of A. marmelos significantly decreased triglyceride, total cholesterol, alkaline the blood sugar level of STZ induced diabetic phosphatase, asperate amino transferase, rabbits44. A. marmelos would act like insulin in alanine amino transferase and creatinine levels the restoration of blood sugar and body weight of STZ induced diabetic rats36. to normal levels in rat and was therefore recommended as a potential hypoglycemic Syzygium cumini (MYRTACEAE) [Fig.28] agent45. Mycaminose a compound isolated from the Elavarasi et al26 reported that the leaves of A. plant S. cumini seed extract. Oral administration marmelos are used by Tribals of Kolli Hills as an of a compound (50 mg/kg), ethyl acetate (200 important ingredient in the poly herbal diabetic mg/kg) and methanol extracts (400 mg/kg) of drug formulations. fruits and leaves of S. cumini reduced the blood glucose level of STZ-induced diabetic rats37. S. Salvadora oleoides (SALVADORACEAE) cumini seed powder and ethanol extract S. [Fig.35] Oral administration of ethanolic extract cumini seed have potential antihyperlipidemic of S. oleoides (1 and 2 g/kg bw) aerial parts effect in type 2 diabetic model rats38. Elavarasi significantly reduced the blood glucose level and et al26 reported that the seed powder of S. cumini improves lipid profile in euglycemic as well as reduced the blood glucose level. alloxan induced diabetic rats46.

Biophytum sensitivum (OXALIDACEAE) Selaginella tamariscina (SELAGINELLACEAE) [Fig.29] Oral administration of the ethanolic [Fig.36] The ethanolic extracts of S. tamariscina extract of B. sensitivum whole plant significantly whole plant ameliorated the fasting blood decreased the blood glucose level, serum glucose level and improved oral glucose cholesterol level and increased the total protein tolerance in STZ induced diabetic rats47. It level of alloxan induced diabetic rats39. significantly lowered the total cholesterol (TC), Phyllanthus reticulatus (PHYLLANTHACEAE) triglyceride (TG), LDL-c, free fatty acids (FFA), [Fig.30] tumor necrosis factor (TNF), ALT, AST, blood Treatment with petroleum ether and ethanolic urea nitrogen (BUN) and malondialdehyde extracts of P. reticulatus (1000 mg/kg) leaves (MDA) levels of diabetic rats47.

986 IJPCBS 2013, 3(3), 983-992 Saravanan K et al. ISSN: 2249-9504

The present review revealed the plant species Solanum xanthocarpum (SOLANACEAE) belonging to Euphorbiaceae (3 species), [Fig.37] Moraceae (3 species), (3 species), The methanolic extract of both the leaves (field Annonaceae (2 species), Malvaceae (2 species) grown and in vitro raised) of S. xanthocarpum at and Myrtaceae (2 species) families have most a dose of 200 mg/kg given orally, significantly potent hypoglycaemic effects. The most reduced the blood glucose level, urea, uric acid commonly used studied species are Trigonella and creatinine level and increased the serum foenum graecum, Senna auriculata, Cinnamonum insulin level in alloxan induced diabetic rats48. zeylanicum, Hibiscus rosa sinensis, Syzygium cumini and Aegle marmelos. Guazuma ulmifolia (STERCULIACEAE) The methods used in the experiments are [Fig.38] Treatment with G. ulmifolia bark diverse. The diabetic model that was most induced the glucose uptake in insulin-resistant commonly used was the streptozotocin- and adipocytes, in addition to its lack of pro- alloxan-induced diabetic rats or mouse to obtain adipogenic or anti-adipogenic effects in murine diabetic models. Scientific validation of several 3T3-F442A preadipose cell line49. It exerted its Indian medicinal plant species has proved the anti-diabetic effects by stimulating glucose efficacy of the botanicals in reducing the sugar uptake in both insulin sensitive and insulin- level. From the reports on their potential resistant adipocytes without inducing effectiveness against diabetes, it is assumed that adipogenesis49. the botanicals have a major role to play in the management of diabetes, which needs further Vitex negundo (VERBANACEAE) [Fig.39] exploration for necessary development of drugs Idopyranose is a compound isolated from the and nutraceuticals from natural resources. leaves of V. negundo (50mg/kg bw) reduced the In conclusion, this paper has presented a list of blood glucose level, serum urea, and cholesterol anti-diabetic plants used in the treatment of level in STZ-induced diabetic rats. It helped to diabetes mellitus. It showed that these plants regenerate the damaged pancreas and protected have hypoglycemic effects. Many new bioactive the pancreatic ß cells and hyperglycemic in drugs isolated from plants having nature against STZ-induced diabetic rats50. hypoglycaemic effects showed antidiabetic Elavarasi et al26 made an Ethnobotanical study activity equal and sometimes even more potent in the Kolli hills of Tamil Nadu, through an oral than known oral hypoglycaemic agents. interview to investigate the medicinal plants However, many other active agents obtained used in the treatment of diabetes. They from plants have not been well characterized. reported 16 species of plants belonging to 14 More investigations must be carried out to families were commonly used by the tribal evaluate the mechanism of action of medicinal peoples to treat diabetes and its related illness. plants with antidiabetic effect. The toxic effect Among the 16 plant species, Cassia auriculata, of these plants should also be elucidated. Hibiscus rosa sinensis, Syzygium cumini and Aegle marmelos were also reported their antidiabetic ACKNOWLEDGEMENT activity by several authors23,32,37 & 44. Authors thank the Management, the Principal Diabetes mellitus is a metabolic disorder and Head of the Department of Zoology, Nehru attributed to diminished production of insulin Memorial College, Puthanampatti. First author or resistance to its action. In order to prevent acknowledges the National Testing Service- this alarming health problem, the development India, Central Institute of Indian Languages, of research in to new hypoglycaemic and Mysore for financial support. All Plant potentially antidiabetic agents is of great photographs were downloaded from Google interest. website. We thank the website authorities for their open source free down load plant images.

987 IJPCBS 2013, 3(3), 983-992 Saravanan K et al. ISSN: 2249-9504

Table 1: Medicinal plants used to treat diabetes S. No. Botanical name Common name Family Parts used 1. Acorus calamus Sweet flag Acoraceae Rhizome 2. Sclerocarrya birrea Jelly plum Anacardiaceae Stem bark 3. Annona squamosa Sugar apple Annonaceae Roots 4. Polyalthia longifolia Buddha Annonaceae Bark 5. Ferula asfoetida Stinking gum Apiaceae Resin 6. Catahranthus roseus Rose peri winkle Apocyanaceae Leaves 7. Ichnocarpus frutescens Black creeper Apocyanaceae Leaves 8. Acanthopanax senticosus Siberian ginseng Araliaceae Stem bark 9. Caralluma sinaica Caralluma Asclepiadaceae Root&aerial parts 10. Terminalia bellerica Belliric myrobalan Combretaceae Fruits 11. Costus speciosus Crepe ginger Costaceae Rhizome 12. Vaccinium bracteatum Sea bilberry Ericaceae Leaves 13. Jatropha curcas Physic nut Euphorbiaceae Leaves 14. Secrinega virosa White berry bush Euphorbiaceae Leaves 15. Emblica officinalis Indian Gooseberry Euphorbiaceae Seed 16. Trigonella foenum graecum Fenu greek Fabaceae Seeds 17. Senna auriculata Tanner’s cassia Fabaceae Leaves 18. Ougeinia oojeinensis Sandan Fabaceae Bark 19. Cinnamonum zeylanicum Cinnamon Lauraceae Bark Essential oil of 20. Allium cepa Onion Liliaceae red onion 21. Strychonous potatorum Clearing nut tree Loganiaceae Whole plant 22. Adansonnia digitata Baobab Malvaceae Stem bark Aerial parts & 23. Hibiscus rosa sinensis Chinese hibiscus Malvaceae flower 24. Ficus benghalensis Indian fig Moraceae Stem bark 25. Ficus glomerata Cluster fig tree Moraceae Leaves 26. Ficus religiosa Sacred tree Moraceae Bark 27. Psidium guajava Guava Myrtaceae Unripe fruit peel 28. Syzygium cumini Java plum Myrtaceae Fruits & leaves 29. Biophytum sensitivum Siker pud Oxaildaceae Whole plant 30. Phyllanthus reticulates Black honey shrub Phyllanthaceae Leaves 31. Rumex patientia Garden patience Polygonaceae Seed 32. Posidonia oceanic Neptune grass Posidoniaceae Leaves 33. Bruguirea gymnorrhiza Black Rhizoporaceae Roots 34. Aegle marmelos Bael tree Rutaceae Leaf&callus 35. Salvadora oleoides Salvadora Salvadoraceae Aerial parts 36. Selaginella tamariscina Resurrection fern Selaginellaceae Whole plant 37. Solanum xanthocarpum Yellow berried night shade Solanaceae Leaves 38. Guazuma ulmifolia Bay cedar Sterculiaceae Bark 39. Vitex negundo Five leaved chaste tree Lamiaceae Leaves

988 IJPCBS 2013, 3(3), 983-992 Saravanan K et al. ISSN: 2249-9504

Fig.1: Acorus Fig.2: Sclerocarya Fig.3: Annona Fig.4: Polyalthia Fig.5: Ferula calamus birrea squamosa longifolia asafoetida

Fig.6: Fig.7: Ichnocarpus Fig.8: Fig.9: Caralluma Fig.10: Terminalia Catharanthus frutescens Acanthopanax sinaica bellerica roseus senticosus

Fig.11: Costus Fig.12: Vaccinium Fig.13: Jatropha Fig.14: Securinega Fig.15: Emblica speciosus bracteatum curcas virosa officinalis

Fig.16: Trigonella Fig.17: Senna Fig.18: Ougeinia Fig.19: Fig.20: Allium foenum graecum auriculata oojeinensis Cinnamonum cepa zeylanicum

Fig.21: Fig.22: Fig.23: Hibiscus Fig.24: Ficus Fig.25: Ficus Strychonous Adansonnia rosa sinensis benghalensis glomerata potatorum digitata

989 IJPCBS 2013, 3(3), 983-992 Saravanan K et al. ISSN: 2249-9504

Fig.26: Ficus Fig.27: Psidium Fig.28: Syzygium Fig.29: Biophytum Fig.30: religiosa guajava cumini sensitivum Phyllanthus reticulatus

Fig.31: Rumex Fig.32: Posidonia Fig.33: Bruguiera Fig.34: Aegle Fig.35: Salvadora patientia oceanica gymnorrhiza marmelos oleoides

Fig.36: Selaginella Fig.37:Solanum Fig.38: Guazuma Fig.39: Vitex negundo tamariscina xanthocarpum ulmifolia Plate 1: Medicinal plants with potential of antidiabetic activities

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