Current Trends of Plants Having Antidiabetic Activity: A Review Bioanalysis Biomedicine

Medicinal plants have been proposed as rich yet unexploited potential sources for antidiabetic drugs, even though used since ancient times for the treatment of diabetes mellitus. Many of the synthetic drugs were discovered either directly or indirectly from the plant source. The present study reviews of plants having antidiabetic property. Although many plants are recommendation, further pharmacological and chemical research should be done to elucidate the exact mechanism of hypoglycemic activity.


Introduction
Diabetes mellitus is a metabolic disorder, characterized by chronic hyperglycemia, with disturbances of carbohydrate, fat and protein metabolism, resulting defects in insulin secretion, insulin action, or both [1]. More than 347 million people are affected by diabetes worldwide [2]. The prevalence of diabetes has risen from 2.4% to 6.4% in the last 15 years [3]. Diabetes related deaths are more common in the low and middle-income countries where more than 80% deaths occur [4].The World Health Organization projects that diabetes will be the 7 th leading cause of death in 2030 [5].
Traditional, complementary and alternative medicines have been used since ancient times. Yet the use of traditional medicine (TM) remains widespread in developing countries, while use of complementary and alternative medicine (CAM) is increasing rapidly in developed countries. In many parts of the world, policy-makers, health professionals and the public are wrestling with questions about the safety, efficacy, quality, availability, preservation and further development of this type of health care. TM is sometimes also the only affordable source of health care especially for the world's poorest patients [6].
Indian traditional health care system uses a number of medicinal plants traditionally over 1000 years in herbal preparations. Medicinal plants, minerals and organic matter cover a major part of traditional medicines. Most of the Indian traditional medical practitioners formulate and dispense their own recipes. 21,000 plants are listed by the WHO, which are used for medicinal purposes around the world. Among these, 2500 species are in India, out of which, 150 species are used commercially on a fairly large scale. India is the largest producer of medicinal herbs and is called the botanical garden of the world [7][8][9][10][11]. Ethnobotanical information reports about 800 plants which possess anti-diabetic potential [12].
TM/CAM is used to treat 200 million patients annually. WHO Regional office reports that 71% of the population in Chile and 40% of the population in Colombia are using TM. Many developed countries uses CAM 46% in Australia, 49% in France and 70% in Canada [13][14][15][16][17]. Even though plant sources are potential antidiabetic drugs, they have not gained sufficient momentum among the scientific community. The present study reviews the medicinal plants used for antidiabetic activity.

Materials and Methods
A current review was done by selecting 50 research papers with antidiabetic effect from plant sources ( Table 1).

Results
Investigations of medicinal plants with different species and families were studied. Different parts of the plants were used for the antidiabetic study. The methanol, ethanol and aqueous solvents were most commonly used for the extractions. The preliminary phytochemical analyses mostly show the presence of terpenoids and flavonoids. Efficacy evaluation of medicinal plants was done by streptozotozine or alloxone induced diabetic modules. Most of the research results showed the hypoglycaemic effects and almost the same effect of standard drugs. Numerous mechanisms of action had been proposed for the plant extracts.

Discussion
Diabetes is a chronic disease that occurs when the body cannot produce enough insulin or cannot use insulin effectively [69]. It is projected that 300 million people will have the disease by the year 2025 [70] and it may reach to 366 million in the year 2030 [71]. Type 2 diabetes is a common condition and a serious global health problem. In most countries, diabetes has increased alongside rapid cultural and social changes: ageing populations, increasing urbanisation, dietary changes, reduced physical activity and unhealthy behaviours [72]. A person's risk of developing Type 2 Diabetes Mellitus has been shown to be highly linked to obesity and any family history of diabetes [73]. Hyperglycaemic condition causes increased glycosylation leading to biochemical and morphological abnormalities due to altered protein structure and develop the neuropathy, retinopathy, neuropathy and cardiomyopathy [74]. Diabetes kills 1.1 million people in 2005 and more than 220 million people worldwide have diabetes, almost 80% of -Alpha Amylase inhibitory activity. [28] 12 Root Ethanol Alloxan/The extract fraction casused a significant (P<0.001) reduction in fasting blood glucose of the diabetic rats both in acute and study and prolonged study (2 weeks). The overall activities of the plant extraction were more than that of the reference drug, Glibenclamide. By stimulation of few surviving β cell to release more insulin. [33] 17 root Alcohol Streptozotocin/The dose dependent reduction in fasting blood glucose level and glucose tolerance test showed better tolerance of glucose in treated rats. Decrease in lipid peroxides and increase in superoxide dismutase and catalase. Significant reduction in triglycerides, total cholesterol and high density lipo-protein cholesterol.
Over production and decreased utilisation of the tissues.
[34] Potentiation of pancreatic secretion of insulin from existing β-cells of islets by the significant increase in the level of insulin. [51] 35 stem Alcohol Streptozotocin/Significant reduction in blood glucose levels and improvement in plasma insulin levels. The effect was more pronounced in 100 and 200 mg/kg than 50 mg/kg. The extract showed significant increase in hexokinase, Glucose-6-phosphate dehydrogenase and glycogen content in liver of diabetic rats and significant reduction in the levels of glucose-6-phosphatase and fructose-1,6bisphosphatase.
Potentiation of pancreatic secretion of insulin from existing β -cells of islets and significant increase in the level of insulin. [52] 36 suspension cell Ethanol Alloxan/ Oral administration of the extracts reduced the glucose content in blood and urine, sugar and lipids in serum significantly (P<0.5) at the same time the extract increase the body weight, total hemoglobin and plasma protein content.
Potentiating the insulin effect of plasma by increasing either the pancreatic section in insulin form β-cell or its release bound form. [53]

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Whole plant Alcohol Streptozotocin/ Significant increase in the body weight and decrease in blood glucose level with higher antioxidant capacity ,good reducing power, scavenger of reactive oxygen like DPPH, nitric acid, hydrogen peroxide and deoxyribose.
Enhance the peripheral utilisation of glucose. [54]

leaves Ethanol and Aqueous
Streptozotocin/In showed an outstanding hypoglycaemic effect at 500 and 1000 mg/kg doses, 1-4 h after the administration.
In oral glucose tolerance test, glucose solution was loaded to normal rats just after 30 th minute measurement. The ethanol extract, given in 1000 mg/kg, was found more effective (3.2-11.7%).
Terpenoids, fatty acids and other hydrocarbons.
Effect in insulin secretion or insulin like activity. Rising sensitivity of PPAR-γ receptors by increasing the release of insulin from β cells of pancreas. [55] 39 flowers Petroleum ether Streptozotocin/21 days of oral administration of extract significantly reduced the blood glucose, serum cholesterol and triglycerids levels. At the same time the high density lipoprotein level was found to be improved (P<0.01).

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Whole plant Methanol Streptozotocin/ Significant decrease in blood glucose and glycosylated hemoglobin with a significant increase in plasma insulin level, body weight and food intake. Furthermore γ-sitosterol showed anti-hyperlipidemic activity as evidenced by significant decrease in serum total cholesterol, triglycerides and very low density lipoprotein-cholesterol levels coupled with elevation of high density lipoprotein-cholesterol levels. A significant decrease in the alanine aminotransaminase, aspartate aminotransaminase, alkaline phosphatase and acid phosphatase in γ-sitosterol treated rats when compared to diabetic control rats indicated its protective role against liver damage.
Immunostimulatory effect and protect the pathological damages secondary to the diabetic complications. The antidiabetic activity is evidently due to flavonoid content of the plant. [58]

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Aerial part Aqueous Alloxan/Significant effect antidiabetic and antihyperlipidemic (dose-dependent effect). A decrease in blood glucose by 50% for the dose 100 mg/ kg and more than 60% for doses 200 and 300 mg/kg twice daily for 2 weeks showed the best decrease in the blood glucose level comparable to the effects of glibenclamide, as well as a significant lowering of total lipids, triglycerides, and total cholesterol levels in treated animals, compared with diabetic controls group (p<0.001), have been observed. The mechanism of these hypoglycemic effects of the extracts is not elucidated in this study.
[68] diabetes deaths occur in low-and middle-income countries [75]. Antidiabetic drugs used as mono-therapy or in combination to achieve better glycemic control. Each of the oral antidiabetic agents is however, associated with a number of serious adverse effects [76,77] and none of the antidiabetic drugs could give a long term glycaemic control without cousin the side effects [78]. Plant based drugs have been known to be safe and cheaper and the plant play the major role to manage the diabetes mellitus [79][80][81]. World health organisation (WHO) has recommended the evaluation of traditional plant treatments for diabetes as they are effective, non-toxic, which less or no side effects and are considered to be a valuable source for the investigation of hypoglycaemic agents [82,83]. According to world ethnobotanical information reports, almost 800 plants possess antidiabetic potential [84]. Several reviews on the plants used in the management of diabetes have been reported in the past [85][86][87][88][89][90][91][92].The current review showed that plants possessed antidiabetic property and may of the study not properly mention the precise mechanism of the plant and the active compound responsible for the antidiabetic effect. This may be explained by the nature of extracts and lack of in vivo methods. Most of the authors explained that the mechanism of the plant extract is the same as that of standard drugs and that the antidiabetic effect is due to the antioxidant property of the plants [18,23,39,47]. Some other authors had mentioned the mechanism of the plant is by increasing the insulin secretion by stimulating the β cell [51][52][53][54][55][62][63][64][65]. However the exact mechanism is very challenging to identified and explained in proper manner. Streptozotocin and alloxan induced diabetes model is used as a screening method for anti-diabetic drugs and many other animal models have been developed and described for the screening of anti-diabetic drugs, but none of them is exactly equivalent to human diabetes [93]. Plant products are known to be rich in phenolic compounds, flavonoids, terpenoids, coumarins and other constituents which reduce blood glucose levels [94,95]. In the current review most of the plants have the flavonoid, and terpenoids may be the reason for reducing the blood glucose level in animals. In Africa, hundreds of plants are used traditionally for the management of diabetes mellitus, but only few of the plants have been scientifically validated [96,97].
The variety of phytoconstituent classes and the wide differences in the molecular structure of the isolated compounds suggest the possibility of different mechanisms of action in lowering blood glucose [98]. So, the identification of phytochemical is not only enough, at the same time prove the exact mechanism and clinical trial is essentially need to use the plant drug clinically.

Conclusion
The study found that since the antidiabetic evaluation is done using extracts. It may be difficult to find the exact mechanism responsible for the hypoglycemic effect. Studies are needed to identify the active compound responsible for the hypoglycemic effect. Although numerous medicinal plants have anti diabetic effect, phytochemical and clinical research work on the discovered plant species is yet to be done. Every plant material is not safe, so need to investigate the toxic effect of these plants before consumption. Isolate and test the active components from the potent active antidiabetic plant and there is the essential need for clinical research on the new drug available in the market with less side effects.