MEDICINAL PLANTS POTENTIAL AGAINST DIABETES MELLITUS: REVIEW ARTICLEHTML Full Text
MEDICINAL PLANTS POTENTIAL AGAINST DIABETES MELLITUS: REVIEW ARTICLE
Sina M. Matalqah * 1, 2 and Deniz M. Al-Tawalbeh 1, 3
Department of Pharmaceutics 1, Faculty of Pharmacy, Jordan University, Amman, 11942, Jordan.
Jordan Ministry of Health 2, Amman, 11118, Jordan.
Department of Applied Science 3, Al- Balqa Applied University, Salt, 19117, Jordan.
ABSTRACT: Diabetes mellitus (DM), both type I and type II, is a common metabolic disorder worldwide. It is characterized by hyperglycemia, lipid, and protein metabolism abnormalities, and accompanied by several clinical complications including retinopathy, neuropathy, and nephropathy. Many traditional herbs have been used for the treatment of DM. In the present review, we showed a list of these herbs describing their growth area, anti-diabetic properties, their active constituent, and mechanism of action. From the review, the anti-diabetic activity of herbs is largely attributed to the presence of polyphenols, flavonoids, terpenoids, and coumarins. Also, this review strongly suggests these herbs as a natural and safe alternative treatment to the regularly used chemical anti-diabetic therapies.
Diabetes, Hyperglycemia, Herbal medicine, Anti-diabetic
INTRODUCTION: Diabetes mellitus (DM) is a common metabolic disorder affecting many people worldwide. According to the World Health Organization (WHO), the diabetic population is likely to increase up to 300 million or more by the year 2025. About 10% of deaths are related to DM. Thus, it is characterized by chronic hyperglycemia usually lead to neuropathy, retinopathy, nephropathy, and cardiovascular diseases. These are the leading causes of morbidity and mortality in diabetic patients 1, 2, 3. DM is caused by either inadequate secretion of the hormone insulin, inadequate response of target cells to insulin, or a combination of these factors. It is known to have a strong genetic component.
DM is characterized by resistance to insulin associated with excess glucose production in the liver and impaired or decreased glucose utilization peripherally, particularly in muscles 4, 5. There is no cure from DM and prevention of its long-term complications represents a mainstay global problem 4, 5, 6. The currently available synthetic therapies for diabetes include insulin and various oral hypoglycemic agents such as sulfonylureas, biguanides, and glinides. However, these modalities have some serious adverse effects; therefore, finding out a reliable and safe treatment is important area of research.
The traditional medicines demonstrated a bright future in the treatment of many diseases including diabetes. The ethnobotanical information revealed that about 800 plants may have anti-diabetic potential and showed beneficial effects in either treatment or prevention of diabetes complications. Anti-diabetic activity of medicinal plants is mainly due to their ability to restore the function of pancreatic cells by causing an increase in insulin secretion or by inhibition of intestinal absorption of glucose. The main active constituents of the plants are polyphenols, flavonoids, terpenoids, carotenoids, and coumarins.
This article reviews and emphasize the importance of some medicinal plants in the treatment of diabetes-associated complications.
Medicinal Herbs Used in Treatment of Diabetes: Plants have always been an excellent source of drugs, and many of the currently available drugs have been derived from them. The ethnobotanical surveys suggest that about 800 plants may possess anti-diabetic potential 7. Some of these herbs might reduce blood glucose levels or might be useful for management of the disease complications 8. Several reports explored the anti-diabetic activity as herbs contain different types of biological components. Among these alkaloids, glycosides, galactomannan gum, polysaccharides, peptidoglycans, hypoglycin, guanidine, steroids, carbohydrates, glycopeptides, terpenoids, amino acids, and inorganic ions have demonstrated activity including treatment of diabetes 9, 10, 11.
Botanical Components for Diabetes Treatment: The aim of the present review is to collect the data available on anti-diabetic plants and show the phytoconstituents having insulin mimetic or secretagogue activities.
Acacia arabica (Leguminosae): About 94% seed diet of Acacia arabica showed a hypoglycemic effect in rats through the release of insulin. However, powdered seeds of Acacia arabica at 2, 3 and 4 g/kg, p.o. exerted a significant hypoglycemic effect in normal rabbits by initiating the release of insulin from pancreatic beta cells 12.
Aegle marmelos (Rutaceae): Aqueous leaf extract of Aegle marmelos showed anti-hyperglycemic activity in streptozotocin-induced diabetic rats after 14 days treatment either by increasing utilization of glucose or by direct stimulation of glucose uptake through increased insulin secretion 13.
Agrimony eupatoria (Rosaceae): Aqueous extract of Agrimony eupatoria evoked stimulation of insulin secretion from the BRIN-BD11 pancreatic beta cell line in-vitro. The effect of the extract was found to be glucose independent 14.
Alangium salvifolium (Alangiaceae): Methanolic extract of Alangium salvifolium leaves possesses anti-hyperglycemic and anti-hyperlipidemic effects in dexamethasone-induced insulin resistance in rats, which may be due to the antioxidant and insulinotropic effect of extract 15.
Annona muricata (Annonaceae): A. muricata played an important role in the reduction of oxidative stress of pancreatic β-cells of streptozotocin-induced diabetic rats, which was confirmed by the increased area of insulin immunoreactive β-cells and protection against degeneration of β-cells 16.
Annona squamosa (Annonaceae): Annona squamosa commonly called custard apple plant possesses anti-diabetic activity. It acts by promoting insulin release from the pancreatic islets, increasing utilization of glucose in muscle and inhibiting the glucose output from liver 16.
Asparagus racemosus (Liliaceae): The ethanol extract, hexane, chloroform and ethyl acetate fractions of Asparagus racemosus root were shown to have dose-dependent insulin secretion in isolated perfused rat pancreas, isolated rat islet cells and clonal beta - cells. These findings reveal that constituents of Asparagus racemosus root extracts have insulinotropic activity 17.
Anacardium occidentale Linn. (Anacardiaceae): Herb originated from Brazil, it is used as folk medicine in African countries, mainly in Cameroon, for the treatment of diabetes mellitus. Hypo-glycemic and the protective role of A. occidentale were reported 6, 18. The anti-hyperglycemic and renal protective activities of leaves of this herb were reported in streptozotocin-induced diabetic rats. It reduces diabetes-induced functional & histological alterations in the kidneys. It was shown that the histopathological study of Anacardium occidentale significantly reduced accumulation of mucopolysaccharides in the kidneys of diabetic animal 19.
Annona squamosa L. (Annonaceae): Commonly called custard apple in English and Sharifa in Hindi. It is cultivated throughout India. The pharmacologically active ingredients are present in seeds, leaves and aerial parts of the plant 20. The research reveals that the plant possesses both hypoglycemic and anti-diabetic activity. It acts by enhancing insulin level from the pancreatic islets, increases utilization of glucose in muscle and inhibits the glucose output from the liver. Its margin of safety is high. The extract obtained from leaves of this plant is useful in maintaining healthy blood sugar and cholesterol levels 21.
Annona muricata L. (Annonaceae): Commonly called soursop. It is a small evergreen tree growing 5 to 6 meters in height. Young branches are rusty-hairy, the malodorous leaves, and the plant is evergreen. Annona muricata is indigenous to most of the warmest tropical areas in South and North America, including the Amazon. The researchers revealed the immuno-histochemical and biochemical effects of aqueous extract of leaves on pancreatic β cells of STZ (streptozotocin) treated diabetic rats. A. muricata Linn. leaf extract played an important role in the reduction of oxidative stress on pancreatic β cells of streptozotocin-treated diabetic rats. The treatment increased the area of insulin immunoreactive β-cells and partially prevents degeneration of β-cells 22.
Allium sativum (Liliaceae): Found in many kitchens - Allium sativum (garlic) - has also been used for medicinal purposes around the world. A majority of contemporary medical use and research for garlic has focused on the treatment of cardiovascular-related diseases. In clinical trials, garlic supplementation among patients with dyslipidemia produced a modest reduction in total cholesterol with no significant changes in LDL or HDL cholesterol levels 23, 24.
Pooled data from clinical trials of patients with hypertension have shown significant decreases in systolic (8.4 ± 2.8 mmHg) and diastolic (7.3 ± 1.5 mmHg) blood pressure levels in patients using garlic treatment compared to control groups. Less research has been conducted among patients with diabetes. Limited animal studies have suggested that the chemical components of garlic may increase insulin secretion or decrease degradation 23, 24. Clinical trials of oral garlic in patients with type II diabetes have not demonstrated significant changes in blood glucose or insulin levels 25, 26.
Aloe vera (Liliaceae): This desert plant is the source of the common gel used topically for dermatological conditions. In the Arabian peninsula, parts of the aloe plant have been used orally as a traditional treatment for diabetes. The gel derived from the meaty pulp of the leaf, taken orally, may produce hypoglycemic effects through β-cell stimulation 27, 28. Two controlled, non-randomized trials in patients with type II diabetes who were given aloe gel juice reported decreases in fasting blood glucose during 6 weeks 28, 29. However, these studies lacked sufficient details in reporting, including study design and results, leading to inconclusive evidence. In contrast to the gel, aloe latex from the inner lining of the leaf contains a harsh anthroquinone laxative that may be unsafe 30.
Boerhaavia diffusa Linn. (Nyctaginaceae): Distributed widely all over in India, is a small perennial creeping herb, commonly known as Red hogweed. The root and the whole plant are used as an Ayurvedic medicine in India and Unani medicine for the treatment of diabetes, stress, dyspepsia, abdominal pain, inflammation, jaundice, enlargement of spleen, congestive heart failure and bacterial infections 16, 31. Aqueous leaf extract of the plant has been studied for its anti-diabetic effect in alloxan-induced diabetic rats 32. The anti-diabetic activity of the chloroform extract of the plant leaves on the chronic treatment of streptozotocin-induced NIDDM (non-insulin dependent diabetes mellitus) model diabetic rats was evaluated, and the herb possesses anti-diabetic activity. The herb mainly acts by reducing blood glucose level and increasing insulin sensitivity 33.
Bougainvillea spectabilis Linn. (Nyctaginaceae): Is a very familiar ornamental plant commonly grown in Indian gardens. Bougainvillea is a genus of flowering plants native to South America from Brazil west to Peru and south to southern Argentina. The traditional plant has anti-diabetic potential.
The blood glucose lowering potential of Bougainvillea spectabilis wild leaf extract in streptozotocin-induced type I diabetic albino rats was reported. The ethanolic extract of the leaves has anti-hyperglycemic activity probably due to increased uptake of glucose by enhanced glycogenesis in the liver and also due to an increase in insulin sensitivity 34.
Bridelia ndellensis Beille. (Euphorbiaceae): A medicinal plant used in Cameroon against diabetes. The water and methanol extract of leaf of allied species B. ferruginea has been proved as an active hypoglycemic agent in alloxan-induced diabetic rats 16.
The study of the glucose lowering of the ethanol extract and fractions of B. ndellensis stem bark in STZ (streptozotocin) type I and II diabetes rats at different prandial states was performed and significant lowering in blood glucose level was observed. The extract act by stimulation of islets cells and requires functional β-cells for its action 35.
Bauhinia variegata (Caesalpiniaceae): Crude ethanolic extract of leaves of Bauhinia variegata and its major metabolite (6S, 7E, 9R)-9-hydroxy megastigma 4,7-dien-3-one-9-beta-glycopyranoside (rose side) have insulinotropic activity in insulin-secreting cell line INS-1, and it was found to be dose-dependent 36.
Berberine: Berberine glucose-stimulated insulin secretion rather promoted than basal insulin secretion in a dose-dependent manner in rat’s pancreatic islets. Berberine can enhance glucose-stimulated insulin secretion in rat islets and probably exerts the insulinotropic effect via a pathway involving hepatic nuclear factor 4 alpha (HNF4) alpha and glucokinase, which is distinct from sulphonylureas 37.
Biophytum sensitivum (Oxalidaceae): Leaf extract of the Biophytum sensitivum stimulates pancreatic beta cells to release insulin in diabetic male rabbits and exerts hypoglycemic activity 13. Administration of the Biophytum sensitivum extract in 16 h fasted non-diabetic rabbits showed a significant rise in the serum insulin levels, which suggested a pancreatic mode of action of Biophytum sensitivum. The hypoglycemic response of Biophytum sensitivum may be mediated through stimulating the synthesis/ release of insulin.
Boerhaavia diffusa (Nyctaginaceae): Chloroform extracts Boerhaavia diffusa leaves showed anti-diabetic activity in streptozotocin-induced diabetic rats which mainly act by reducing blood glucose level and increasing insulin sensitivity 16. Hypoglycemic and anti-hyperglycemic activity of aqueous leaf extract at 200 mg/ kg p.o. for 4 weeks in normal and alloxan-induced diabetic rats showed to increase plasma insulin levels and improve glucose tolerance 13.
Bougainvillea spectabilis (Nyctaginaceae): The blood glucose lowering potential of ethanolic leaf extract of Bougainvillea spectabilis in streptozotocin-induced type I diabetic Albino rats was probably due to increased glucose uptake by enhanced glycogenesis in the liver and also due to increased insulin sensitivity 16.
Brassica nigra (Cruciferae): Oral administration of aqueous extract of Brassica nigra for two months decreased serum glucose level, which was due to the release of insulin from pancreas 38.
Canavalia ensiformis DC. (Leguminaceae): Known as horse bean, the native of Central America and West Indices has been widely cultivated in humid tropics of Africa and Asia. The seeds have been reported to possess anti-hypercholesterolemic 39, and hypoglycemic activities 40. The oral administration of aqueous extract of C. ensiformis seeds reduce urinary and blood glucose levels, and also elevated levels of triacylglycerol, ketone bodies and cholesterol associated with diabetes mellitus 16.
Casearia esculenta Roxb. (Flacourtiaceae): Is a plant with medicinal properties known as wild cowrie fruit in English. The plant is in the form of shrub distributed in South India. C. esculenta has been a remedy which is popular for diabetes mellitus 41, 42, 43. It has been reported that the plant contains hypoglycemic effect 44. C. esculenta root extract contain hypoglycemic factors, which reduced blood sugar level in experimental animals. C. esculenta root extract has an influence on protein metabolism and marker enzymes in streptozotocin-induced diabetic rats. The study revealed that C. esculenta root extract has the anti-hyperglycemic effect and it may elevate liver and renal damage associated with streptozotocin-induced diabetes in rats 45.
Cassia kleinii Wight & Arn. (Caesalpiniaceae): Is the medical remedy for the folk diabetic practitioners in South India. The traditional systems like Ayurveda and Siddha systems do not use this plant. The alcoholic extracts of leaves seem to show promising results for the development of phytomedicines by exhibiting the anti-hyperglycemic activity on glucose feed hyperglycemic and alloxan-induced diabetic rats.
The leaf extract of Cassia kleinii may not act by potentiation of insulin but it could be used in insulin-independent diabetes because drug exhibited anti-hyperglycemic effect but not hypoglycemic effect in fasted rats. The action of drug may be mimicking some or all of the action of insulin on the metabolism of glucose 45.
Catharanthus roseus Linn. (Apocynaceae): Commonly used as an anticancer agent, but the hot water decoction of the leaves and or the whole plant is used for the treatment of diabetes in subtropical and tropical areas of the world 46. The reports indicate blood glucose lowering activity in the alcoholic extract of the leaves of C. roseus. The herb has prophylactic activity against the necrotic actions of alloxan monohydrate 47, 48, 49.
Anti-diabetic activity of a dichloromethane-methanol extract of the leaves and twigs was evaluated and its effect on enzymes of carbohydrate metabolism was studied. The mechanism may be due to enhanced secretion of insulin. The other researchers revealed that extract may be helpful in the prevention of damage caused by oxygen free radicals and increase in glucose utilization 50.
Coccinia indica Wight & Arn. (Cucurbitaceae): Widely used in traditional treatment of diabetes mellitus in sub-Saharan Africa and Southeast Asia. Pectin isolated from the fruits of C. indica has hypoglycemic activity 51. Alcoholic extract of the plant was found to be active in reducing blood glucose level, then this extract was subjected to further fractionation to evaluate its biochemical parameters affecting diabetes and results suggested toluene as an active fraction. The exact action of these principles may be due to their β-cell restorative properties against alloxan-induced damage 52.
Cocculus hirsutus Linn. (Menispermaceae): Roots are bitter, acrid, laxative, demulcent and antiperiodic in fever, tonic, and diuretic, also known as patal garudi. The plant grows all over India, especially in dry regions. It is a straggling shrub, with softly villous young parts and resembles the plant path. Badole et al., have demonstrated the anti-hyperglycemic activity of aqueous extract of leaves of Cocculus hirsutus (L.) Diels in alloxan-induced diabetic mice. The antihyperglycemic potential of aqueous extract of C. hirsutus may be due to the lowering of serum glucose level in diabetic mice and increased glucose tolerance. Additionally, the extract prevents loss of body weight 53.
C. fenestratum Colebr. (Menispermaceae): Commonly known as a tree in Western Ghats (India) and Sri Lanka. The plant has been mainly used for diabetes mellitus in the traditional, Ayurvedic and Siddha systems of medicine. Alcoholic stem extract of this plant regulates metabolism and improves antioxidant status in streptozotocin, nicotinamide-induced diabetic rats. The alcoholic extract regulates glucose homeostasis and decreased gluconeogenesis by Coscinium fenestratum. The drug also has a protective action on cellular antioxidant defense 54.
Coccinia indica (Cucurbitaceae): Ayurveda is a traditional medical system from the Indian subcontinent that often uses herbs for treatment. The creeper plant Coccinia indica (ivy gourd) is prescribed in Ayurveda for the treatment of diabetes. Coccinia may produce hypoglycemia in a mechanism similar to insulin 55.
Two randomized, controlled trials (RCTs) 56, 57, and one controlled, nonrandomized trial 57 have suggested decreases in fasting blood glucose without adverse effects among type II diabetes patients after administration of Coccinia.
Cinnamon zeylaniucm (Lauraceae): In-vitro incubation of pancreatic islets with cinnamaldehyde isolated from Cinnamon zeylaniucm resulted in enhanced insulin release. The insulinotropic effect of cinnamaldehyde was due to an increase in the glucose uptake through glucose transporter (GLUT4) translocation in peripheral tissues 58.
Caesalpinia bonducella (Caesalpiniaceae): Hypo-glycemic activity of aqueous and ethanolic extracts of Caesalpinia bonducella in chronic type II diabetic model, showed an increased secretion of insulin in isolated islets 13.
Caffeine: Treatment with 0.01% caffeine solution in 90% pancreatectomized diabetic rats for 12-week reduced body weight, fats, and decreased insulin resistance. At the same time caffeine also enhanced glucose-stimulated first- and second-phase insulin secretion and beta-cell hyperplasia 59.
Camellia sinensis (Theaceae): Epigallocatechin gallate, present in Camellia sinensis increases insulin activity and prevents oxidative damages in streptozotocin-induced diabetic rats. The lower dose of Camellia sinensis on SD rats fed with high-fat diet for 2 weeks showed an insulinotropic effect in experimental condition 60.
Capsicum frutescens (Solanaceae): Capsicum frutescens increased serum insulin concentration in a high-fat (HF) diet-fed streptozotocin-induced type II diabetes rats after 4 weeks of treatment. The data of this study suggested that 2% of dietary Capsicum frutescens is insulinotropic rather than hypoglycemic in the experimental methods 61.
Catharanthus roseus (Apocynaceae): Dichloro-methane-methanol extract of leaves and twigs of Catharanthus roseus in carbohydrate metabolism, showed to enhance secretion of insulin. The extract was also found to be helpful in the prevention of damage caused by oxygen free radicals 16.
Citrullus colocynthis (Cucurbitaceae): Citrullus colocynthis pulp extract at 300 mg/kg, p.o. was found to significantly increase insulin and decrease plasma glucose levels in alloxan-induced diabetic rats. Immunohistochemistry procedure showed that the amount of insulin in beta-cells of the islets of Langerhans is more significant in Citrullus colocynthis treated-diabetic rats in comparison to the control group 62. Administration of the ethanol extract of the dried seedless pulp of Citrullus colocynthis at 300 mg/kg, p.o had insulinotropic actions in alloxan-induced diabetic rats 63.
Coccinia indica (Cucurbitaceae): Oral administration of dried extract of Coccinia indica at 500 mg/kg, p.o. for 6 weeks significantly increased insulin concentration in a clinical study. The plant extract showed to exert a beneficial hypoglycemic effect in experimental animals and human diabetic subject possibly through an insulin-secreting effect or through the influence of enzymes involved in glucose metabolism 12.
Cornus officinalis (Cornaceae): Alcoholic extract of Cornus officinalis can increase GLUT4 mRNA and its protein expression in NIDDM rats by promoting proliferation of pancreatic islets and by increasing postprandial secretion of insulin and therefore accelerating the glucose transport 64. Methanol extract and its fractions had potent insulin mimic activity on phosphoenolpyruvate carboxykinase expression. The ability of fractions to protect beta-cell against toxic challenge and to enhance insulin secretion strengthens the role of Cornus officinalis in diabetes therapy 65.
Dioscorea dumetorum Pax. (Dioscoreaceae): Used in the treatment of diabetes in traditional medicine, possesses hypoglycemic effect. D. dumetorum Pax. is commonly known as bitter yam. It occurs in Africa. An alkaloid present in an extract, dioscoretine, has been reported to possess hypoglycemic effect 66. It has been reported that aqueous extract of D. dumetorum tuber control hyperlipidemia, hypercholesterolemia, and hyper-ketonemia. The herb mainly acts as an active hypoglycemic agent and works on the complications of diabetes 67.
Elephantopus scaber (Asteraceae): The acetone extract of Elephantopus scaber showed a significant decrease in blood glucose level by improving insulin sensitivity, augmenting glucose-dependent insulin secretion and stimulating the regeneration of islets of Langerhans in the pancreas of STZ-induced diabetic rats 68.
Enicostemma littorale (Gentianaceae): Aqueous extract of Enicostemma littorale induced serum insulin levels in alloxan-induced diabetic rats at 8 h was associated with potentiation of glucose-induced insulin release through K+-ATP channel-dependent pathway 69.
Ephedra distachya (Ephedraceae): The alkaloids of Ephedra distachya herbs and l-ephedrine have shown an anti-hyperglycemic effect in diabetic mice due to regeneration and restoration of atrophied pancreatic islets that induces the secretion of insulin 64.
Eriobotrya japonica (Rosaceae): Aqueous extract of Eriobotrya japonica and the compounds cinchona in Ib, procyanidin B-2, chlorogenic acid, and epicatechin, were tested for insulin secretory activity in INS-1 cells, showed a significant increase of insulin secretion from INS-1 cells in dose-dependent manner 64.
Eucalyptus globulus (Myrtaceae): Aqueous extract of Eucalyptus globulus (0.5 g/L of solution) increased peripheral glucose utilization in the mouse abdominal muscle and increased insulin secretion from the clonal pancreatic β-cell line 12.
Eugenia jambolana (Myrtaceae): Effect of Eugenia jambolana seeds extract in isolated pancreatic islet cells of normal and diabetic animals was investigated and found that it enhances insulin secretion from cells. Eugenia jambolana extract also inhibited insulinase activity from liver and kidney 12.
Ficus hispida Linn. (Moraceae): Also known as Daduri for the treatment of diabetes. This small tree may be found throughout India. Different workers have reported for the hypoglycemic effects of different compounds obtained from F. bengalensis 16. The hypoglycemic activity of Ficus hispida Linn. (bark) in normal and diabetic albino rats concluded that the water-soluble fraction of the alcoholic extract of Ficus hispida significantly decreases fasting blood glucose levels in normal and alloxan-induced diabetic rats. The extract has direct peripheral action on β cells but drug interaction can occur between Ficus hispida bark extract and insulin if given together 70.
Ficus bengalensis (Moraceae): The oral administration of the extract of Ficus bengalensis caused enhanced serum insulin levels in normoglycaemic and diabetic rats. The increased insulin secretion is mainly due to inhibited insulinase activity from liver and kidney 12.
Fermented Unsalted Soybeans: Effect of fermented unsalted soybeans in 90% pancreatectomized diabetic rats for 8-week enhanced insulin secretion. In addition, Chungkookjang potentiated insulin/IGF-1 signaling in islets via the induction of insulin receptor substrate-2 expression, leading to increased pancreatic duodenal homeobox-1, insulin promoter transcription factor. In parallel with the enhancement of the signaling, Chungkookjang elevated pancreatic beta-cell hyperplasia by increasing its proliferation and decreasing apoptosis 71.
Gymnema sylvestre (Asclepiadaceae): This botanical has also been used for two centuries in Ayurveda for the treatment of diabetes. Traditionally, the leaves of the plant are chewed, which can suppress the sweet taste sensation, giving rise to its Hindi name gurmar, or “sugar destroyer.” In addition to affecting taste, the herb has demonstrated hypoglycemic effects in animal and human studies, perhaps functioning as an insulin secretagogue 72, 73. An extract of Gymnema leaf, called GS4, has been studied as an adjuvant therapy to conventional care in two controlled, nonrandomized trials of patients with type I and type II diabetes, respectively 74, 75.
Both studies reported significant before-to-after improvements in fasting blood glucose and A1C levels among patients receiving GS4. No significant before-to-after changes were reported in the control groups. These studies lacked between-group comparisons and randomization, precluding definitive evidence for Gymnema for the treatment of diabetes.
Genistein: Genistein increases insulin secretion in both insulin-secreting cell lines (INS-1 and MIN6) and mouse pancreatic islets. It was found that genistein directly acts on pancreatic beta-cells, leading to activation of the cAMP/PKA signaling cascade to exert an insulinotropic effect 76.
Ginkgo biloba (Ginkgoaceae): Effect of Ginkgo biloba extract in humans, and healthy rats show that Ginkgo biloba significantly increased the insulin concentration 14.
Gymnema sylvestre (Asclepiadaceae): Alcoholic extract of Gymnema sylvestre stimulated insulin secretion from the rat islets of Langerhans and several pancreatic beta cell lines. In another study, oral administration of a water-soluble leaves extract of Gymnema sylvestre at 400 mg/day, p.o. to 27 IDDM patients on insulin therapy lowered fasting blood glucose and insulin requirements. Pancreatic beta cells may be regenerated or repaired in type II diabetic patients on Gymnema sylvestre supplementation; the raised insulin levels support this in the serum of patients after supplementation 14.
Oral administration of Gymnema sylvestre to diabetic rats increased the number of pancreatic islet and beta cells, as well as insulin levels, suggesting a possible repair or regeneration of the endocrine pancreas. Water-soluble extracts of Gymnema sylvestre leaves release insulin probably by causing regeneration of pancreatic beta cells both in-vivo and in-vitro 77.
H. isora (Sterculiaceae): Anti-hyperglycemic activity of butanol extracts of root of Helicteres isora at 250 mg/kg, p.o. in glucose-loaded rats act through insulin-sensitizing activity 13.
Hibiscus rosa sinensis (Malvaceae): Oral administration of ethanol extract of Hibiscus rosa sinensis at 250 mg/kg, p.o. Showed mild but significant hypoglycemia which was mainly due to insulin release by stimulation of pancreatic β-cells 11.
Hordeum vulgare (Gramineae): The germinant fruits of Hordeum vulgare showed hypoglycemic and hyperinsulinemic effects in NIDDM subjects, due to the mobilization of insulin in NIDDM, which makes it a suitable cereal for diabetes mellitus 64.
H. hemerocallidea Fisch. Mey. (Hypoxidaceae): It is a tuberous perennial plant which was previously known as H. rooperi. It is called the wonder plant in South Africa and has been reported to be an effective remedy for the adult onset diabetes mellitus 78. The methanolic extract of Hypoxis hemerocallidea was reported for its hypoglycemic effect in normoglycaemic and in streptozotocin-induced diabetic rats, the herb can be used as a hypoglycemic agent, and it has property to cure the adult onset diabetes mellitus 79. The action of the herbal plant material is not yet clear.
Lepechinia caulescens (Lamiaceae): Lepechinia caulescens significantly decreased glucose tolerance suggesting that Lepechinia caulescens has insulinomimetic activity 14.
Murraya koenigii Linn. (Rutaceae): Is commonly known as Curry patta and is widely used condiment and spice in India. In normal and alloxan diabetes the aqueous extract of the leaves of M. koenigii produced hypoglycemic effect 80. Oral feeding of this plant for 60 days diet to normal rats showed an increase in the concentration of hepatic glycogen due to hypoglycemic activity 81. It has been reported that feeding different doses of M. koenigii leaves to diabetic rats play a role in the control of mild diabetic rats to moderate, severe and type I diabetes 82. It suppressed the blood glucose level and was found to have a beneficial effect on carbohydrate metabolism 83.
Medicago sativa (Fabaceae): Aqueous extract of Medicago sativa evoked stimulation of insulin secretion from the BRIN-BD11 pancreatic beta cell line in vitro. In another study, it was found that insulin-releasing activity of the methanol and water fractions is mainly due to the cumulative effect of its constituent present in it 14.
Momordica charantia (Cucurbitaceae): Significant reduction of blood glucose level and increased concentration of plasma insulin have been observed in diabetic rats that were treated with fruit juice of Momordica charantia. The observed effect was due to an increase in the number of beta cells in treated animals compared to untreated one. The phytochemical momordicin, charantin, and a few compounds such as galactose-binding lectin and insulin-like protein isolated from various parts of this plant have been shown to have insulin mimetic activity 77.
Aqueous extract of unripe fruits of Momordica charantia has also been shown to partially stimulate insulin release from isolated beta-cell of obese-hyperglycemic mice suggesting that the insulin-releasing action is the result of perturbations of membrane functions. Momordica charantia increases the renewal of partial cells in the pancreas or may permit the recovery of partially destroyed cells and stimulates pancreatic insulin secretion 64.
Mucuna pruriens (Leguminosae): Blood glucose lowering activity of powdered seeds of Mucuna pruriens was observed at 0.5, 1 and 2 g/kg, p.o. in normal rabbits as well as 1 and 2 g/kg, p.o. in alloxan diabetic rabbits. It possibly acts through stimulation of the release of insulin or by a direct insulin-like action due to the presence of trace elements like manganese, zinc, etc. 13
Nigella sativa oil (Ranunculaceae): Significant decreases in blood glucose level an increase in serum insulin level were observed on treatment with Nigella sativa oil for 4 weeks. Immunohistochemical staining of the pancreas from Nigella sativa oil-treated group showed large areas with positive immunoreactivity for the presence of insulin 84.
Opuntia streptacantha (prickly pear cactus, nopal): Found in desert regions of North America, nopal is used in Mexican cuisine and indigenous medicine. Mexican - American patients with diabetes have reported using nopal for glucose control 85. Few studies of nopal have been published in English, and these have explored acute metabolic effects rather than clinical outcomes 86, 87.
Panax ginseng L. (Asian ginseng, Araliaceae): Root has been used clinically in the treatment of type II diabetes throughout Asian countries. Historical records revealed that P. ginseng had been used clinically to treat type II diabetes. In-vitro and in-vivo animal studies and clinical trials support the claim that the roots of this plant possess anti-hyperglycemic activity. The ginsenoside plays important role in anti-hyperglycemic action and other constituents have a distinct pharmacological effect on energy metabolism 88.
Panax quiquefolius (Araliaceae): The Panax genus contains multiple species described as ginseng, with two varieties most frequently used and studied: Panax ginseng (Asian ginseng, Chinese ginseng, Korean ginseng) and Panax quinquefolius (American ginseng). The root of this herb traditionally has been used in Asia and is one of the most popular botanicals in the United States. Ginseng has many proposed health benefits, including improved general well-being, increased concentration, and treatment of cardiovascular disease and diabetes (Panax is cognate to panacea). Ginseng can cause hypoglycemia, perhaps through activity similar to insulin or by altering hepatic glucose metabolism 89.
Buettner et al., in a systematic review 90, found conflicting clinical data of ginseng’s effect on blood glucose in diabetic and non-diabetic populations. Variations in response may reflect chemical heterogeneity of different ginseng batches used in studies 91, 92.
Pandanus odors (Pandanaceae): 4-Hydroxy benzoic acid from Pandanus odors at 5 mg/kg increased serum insulin levels and liver glycogen content in healthy rats 14.
Parinari excelsa (Chrysobalanaceae): Flavonoid of Parinari excelsa showed hypoglycemic effect due to the ability of insulin secretory activity in the diabetic animal models 68.
Prunella vulgaris (Labiatae): Jiangtangsu had been isolated from Prunella vulgaris and confirmed to have remarkable blood sugar lowering effect in diabetic mice. The possible mechanism of Jiangtangsu is to repair cells of pancreatic islet to release insulin 64.
Psidium guajava (Myrtaceae): Flavonoid glycosides such as strictinin, isostrictinin, and pedunculagin are the effective constituents of Psidium guajava, which have been used in clinical treatment of diabetes due to improved sensitivity of insulin 64.
Pterocarpus marsupium (Fabaceae): Flavonoid fraction from Pterocarpus marsupium has been shown to cause pancreatic beta-cell regranulation. Epicatechin, its active principle, has been found to be insulinogenic thus enhancing insulin release and conversion of proinsulin to insulin in-vitro 93.
Radix glycyrrhizae (Fabaceae): Radix glycyrrhizae and glycyrrhetinic acid enhanced glucose-stimulated insulin secretion in isolated islets. In addition, they induced mRNA levels of insulin receptor substrate-2, pancreas duodenum homeobox-1, and glucokinase in the islets, which contributed to improving beta-cell viability 94.
Radix rehmanniae (Scrophulariaceae): The pectin type polysaccharide, obtained from the rhizome of R. rehmanniae exhibited hypoglycemic activity in normal and streptozotocin-induced diabetic mice by stimulating the secretion of insulin and reducing the glycogen content in the mice 64.
Rehmania glutinosa (Scrophulariaceae): Intra-peritoneal administration of the ethanol precipitate fraction obtained from the hot water extract from the rhizome of Rehmania glutinosa stimulated the secretion of insulin and reduced the glycogen content in the livers of healthy mice 14.
Ricinus communis (Euphorbiaceae): Administration of ethanolic extract of Ricinus communis to the diabetic rats at 500 mg/kg, p.o. for 20 days, significantly increased the insulin levels and caused improvement in lipid profile and body weight of the diabetic animals 68.
Syzygium cumini (Rutaceae): Oral administration of pulp extract of the fruit of Syzygium cumini to normoglycaemic and STZ induced diabetic rats showed hypoglycemic activity in 30 min possibly mediated by insulin secretion and inhibited insulinase activity 11.
Salvia lavandifolia (Lamiaceae): Hypoglycemic effect of Salvia lavandifolia may be due to potentiation of insulin release induced by glucose and hyperplasia of the pancreatic islet beta cells along with some other mechanisms. The anti-diabetic activity of the extract of Salvia lavandifolia at 10 mg/kg induced an increase in the size and number of cells in the islets of Langerhans with the increase in pancreatic insulin content 11.
Sarcopoterium spinosum (Rosaceae): The aqueous extract of Sarcopoterium spinosum exhibited an insulin-like effect on glucose uptake in hepatocytes by inducing the increase in glucose uptake. It also increased insulin secretion in-vitro 68.
Selaginella tamariscina (Selaginellaceae): Intra-peritoneal administration of S. tamariscina at 25 g/kg for 12 days produced a decrease in blood glucose and serum lipid peroxide, as well as an increase in the concentration of serum insulin. Histological observations showed that this plant could repair the structure of pancreatic islet beta cells injured by alloxan 14.
Semen coicis (Gramineae): Coixans isolated and purified from the dried Semen coicis seeds, decreased blood glucose in normal rats with increased serum insulin level. The anti-diabetic mechanism of coixans may be due to the prevention of pancreatic beta-cells injury, induced by alloxan 64.
Smallanthus sonchifolius (Asteraceae): Administration of 2% Smallanthus sonchifolius to diabetic rats for 30-day increased levels of circulating insulin, which may be due to increased synthesis and secretion of insulin 95.
Stevia rebaudiana (Asteraceae): Effect of stevioside in isolated mouse islets and the clonal beta cell line INS-1 was investigated and found that glycoside stevioside exerts anti-hyperglycemic, insulinotropic, and glucagonostatic actions in the type II diabetic GK rat 96.
Swertia chirayita (Gentianaceae): Hexane fraction of Swertia chirayita at 250 mg/kg, p.o. to normal rats significantly reduced blood sugar and increased plasma insulin without influencing hepatic glycogen content. However, when administered for 28 days, it significantly increased hepatic glycogen content in conjunction with other effects probably by releasing insulin. Single oral administration of swerchirin (50 mg/ kg) to rats caused a fall in blood glucose with marked depletion of aldehyde fuchsin stained beta-granules and immunostained insulin in the pancreatic islets. Swerchirin at 100, 10 and 1 mM concentration greatly enhanced glucose-stimulated insulin release from isolated islets 11.
Swertia punicea (Gentianaceae): Ethanol extracts and ethyl acetate soluble fraction of Swertia punicea showed hypoglycemic effects in STZ induced type II diabetic mice and may be beneficial to improve insulin resistance 68.
Syzyguim cumini Linn. (Formerly Eugenia jambolana, Myrtaceae): With putative anti-hyperglycemic effects. Many parts of the plant, like fruit, seeds, bark, and tea prepared from the leaves, have been used in the treatment of diabetes throughout Asian countries 97. The anti-hyperglycemic effect has been reported in leaves 98, seeds 99, fruits 100, and bark 101, but researchers failed to identify any blood glucose lowering effect with extracts or tea prepared from leaves of the plant in normal rats and rats with STZ-induced diabetes mellitus, and normal volunteers. Tea prepared from leaves of S. cumini has no hypoglycemic effect but, as its mechanism of action could depend on specific abnormalities with the disease, the effect in diabetes is still possible 102.
Terminalia chebula Retz. (Combretaceae): Has been widely used in diabetes in Ayurveda and is widely distributed in India. An herbal formulation containing T. chebula named Triphala is traditional medicine for the treatment of diabetes. Anti-diabetic and renoprotective effects of the chloroform extract of T. chebula Retz seeds in streptozotocin-induced diabetic rats was proved. It has potent renoprotective action 103.
Terminalia catappa Linn. (Combretaceae): Is found throughout the warmer parts of India and called an Indian almond. The anti-diabetic potential of petroleum ether, methanol and aqueous extract of T. catappa fruits on fasting blood sugar levels and serum biochemical analysis in alloxan-induced diabetic rats was performed. All the three extracts produced a significant anti-diabetic activity at dose levels of 1/5 of their lethal doses. The extract may act by β-cells regeneration. The effect may be due to β-carotine in reducing diabetic complications like glycosylation in alloxan-induced diabetic rats 104.
Trigonella foenum graecum (Leguminosae): Fenugreek is grown in North America and Asia and often flavors Indian food. It has been used as medicine for diabetes in India and China. Mechanisms proposed for fenugreek in diabetes are decreased carbohydrate absorption and increased insulin secretion. Several clinical trials among patients with type I or type II diabetes suggest a potential effect, but studies thus far have lacked sufficient quality 105, 106.
Tabernanthe iboga (Apocynaceae): The effect of an aqueous extract of Tabernanthe iboga augmented glucose-stimulated insulin secretion in a dose-dependent manner. Tabernanthe iboga contains water-soluble insulinotropic compounds. The insulin secretory effect of Tabernanthe iboga might involve the closure of K+-ATP and the intensification of calcium influx through voltage-sensitive Ca2+ channels in rat pancreatic islets of Langerhans 107.
DISCUSSION: Diabetes, a pathological condition characterized by loss of glucose homeostasis, is carbohydrate, fat, and protein metabolism disorder result by insulin insufficiency or due to its resistance 108. The incidence of the disease is increasing all over the world as the disease poses many challenges not only to the physician but also to the researcher. The World Health Organization estimated that about 30 million people suffered from diabetes in 1985 and the number increased to more than 171 million in 2000.
It is estimated that the number will increase to over 366 million by 2030 and that large increases will occur in developing countries, especially in people aged between 45 and 64 years 109. In spite of the presence of known anti-diabetic medicine in the pharmaceutical market, remedies from medicinal plants are used with success to treat this disease.
Previous studies have reported that medicinal plants might be used in the treatment of insulin-dependent and -independent diabetes. Plant drugs and herbal formulations are frequently considered to be less toxic and free from side effects than synthetic ones. Medicinal plant families with the most potent hypoglycemic effects include Leguminaceae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae, Euphorbiaceae & Araliaceae. The most commonly studied species are: Opuntia streptacantha, Trigonella foenum graecum, Momordica charantia, Ficus bengalensis, Polygala senega and Gymnema sylvestre.
The hypoglycemic effect of medicinal plants is attributed to numerous mechanisms. These include their effects on the activity of pancreatic beta cells, increase in the inhibitory effect against insulinase enzyme, the increase of the insulin sensitivity or the insulin-like activity of the plant extracts. Other mechanisms may also be involved such as increase of peripheral utilization of glucose, an increase of synthesis of hepatic glycogen or decrease of glycogenolysis, inhibition of intestinal glucose absorption, reduction of glycaemic index of carbohydrates and reduction of the effect of glutathione 14. In this review, plant extracts containing terpenoids, alkaloids, flavonoids, or phenolic compounds have shown antidiabetic potential through the insulinomimetic activity. Roseoside, epigallocatechin gallate, beta-pyrazole-1- ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d- galactosyl cellobioside, leucopelargonidin-3-O-alpha-L rhamnoside, glycyrrhetinic acid, dehydro-trametenolic acid, strictinin, isostrictinin and pedunculagin, epicatechin and christinin-A isolated from the plant material have shown significant insulinomimetic activity along with significant anti-diabetic potential 110.
CONCLUSION: In conclusion, this review has presented a list of anti-diabetic plants used in the treatment of diabetes mellitus. It showed that these plants have hypoglycemic effects and can be used to treat various types of secondary complications of diabetes mellitus.
CONFLICT OF INTEREST: The authors declare no conflict of interest.
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How to cite this article:
Matalqah SM and Al-Tawalbeh DM: Medicinal plants potential against diabetes mellitus: Review article. Int J Pharmacognosy 2019; 6(2): 39-53. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.6(2).39-53.
This Journal licensed under a Creative Commons Attribution-Non-commercial-Share Alike 3.0 Unported License.
S. M. Matalqah * and D. M. Al-Tawalbeh
Department of Pharmaceutics, Faculty of Pharmacy, Jordan University, Amman, Jordan.
17 January 2019
21 February 2019
23 February 2019
28 February 2019