DIABETES;;;Traditional Medicines derived from medicinal plants are used by about 60% of the world’s population. This review focuses on Herbal drugs and plants used in the treatment of diabetes.. Diabetes is an important human ailment afflicting many from various walks of life in different countries. It is proving to be a major health problem, especially in the urban areas. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, herbal formulations are preferred due to lesser side effects and low cost. One of the etiologic factors implicated in the development of diabetes and its complications is the damage induced by free radicals and hence an antidiabetic compound with antioxidant properties would be more beneficial. Therefore information on antioxidant effects of these medicinal plants is also included.

In the last few years there has been an exponential growth in the field of herbal medicine and these drugs are gaining popularity both in developing and developed countries because of their natural origin and less side effects. Many traditional medicines in use are derived from medicinal plants, minerals and organic matter.

Diabetes and Significance
Diabetes is a chronic disorder of carbohydrate, fat and protein metabolism characterized by increased fasting and post prandial blood sugar levels. The global prevalence of diabetes is estimated to increase, from 4% in 1995 to 5.4% by the year 2025. WHO has predicted that the major burden will occur in developing countries. Studies conducted in the last decade have highlighted that not only is the prevalence of diabetes high but also that it is increasing rapidly in the urban population.

Diabetes mellitus is a complex metabolic disorder resulting from either insulin insufficiency or insulin dysfunction. Type I diabetes (insulin dependent) is caused due to insulin insufficiency because of lack of functional beta cells. Patients suffering from this are therefore totally dependent on exogenous source of insulin while patients suffering from Type II diabetes (insulin independent) are unable to respond to insulin and can be treated with dietary changes, exercise and medication. Type II diabetes is the more common form of diabetes constituting 90% of the diabetic population. Symptoms for both diabetic conditions may include: (i) high levels of sugar in the blood; (ii) unusual thirst; (iii) frequent urination; (iv) extreme hunger and loss of weight; (v) blurred vision; (vi) nausea and vomiting; (vii) extreme weakness and tiredness; (viii) irritability, mood changes etc.

Though pathophysiology of diabetes remains to be fully understood, experimental evidences suggest the involvement of free radicals in the pathogenesis of diabetes [5] and more importantly in the development of diabetic complications [6–8]. Free radicals are capable of damaging cellular molecules, DNA, proteins and lipids leading to altered cellular functions. Many recent studies reveal that antioxidants capable of neutralizing free radicals are effective in preventing experimentally induced diabetes in animal models [9, 10] as well as reducing the severity of diabetic complications [8].

For the development of diabetic complications, the abnormalities produced in lipids and proteins are the major etiologic factors. In diabetic patients, extra-cellular and long lived proteins, such as elastin, laminin, collagen are the major targets of free radicals. These proteins are modified to form glycoproteins due to hyperglycemia. The modification of these proteins present in tissues such as lens, vascular wall and basement membranes are associated with the development of complications of diabetes such as cataracts, microangiopathy, atherosclerosis and nephropathy [11]. During diabetes, lipoproteins are oxidized by free radicals. There are also multiple abnormalities of lipoprotein metabolism in very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) in diabetes. Lipid peroxidation is enhanced due to increased oxidative stress in diabetic condition. Apart from this, advanced glycation end products (AGEs) are formed by non-enzymatic glycosylation of proteins. AGEs tend to accumulate on long-lived molecules in tissues and generate abnormalities in cell and tissue functions [12, 13]. In addition, AGEs also contribute to increased vascular permeability in both micro and macrovascular structures by binding to specific macrophage receptors. This results in formation of free radicals and endothelial dysfunction. AGEs are also formed on nucleic acids and histones and may cause mutations and altered gene expression.

As diabetes is a multifactorial disease leading to several complications, and therefore demands a multiple therapeutic approach. Patients of diabetes either do not make enough insulin or their cells do not respond to insulin. In case of total lack of insulin, patients are given insulin injections. Whereas in case of those where cells do not respond to insulin many different drugs are developed taking into consideration possible disturbances in carbohydrate-metabolism. For example, to manage post-prandial hyper-glycaemia at digestive level, glucosidase inhibitors such as acarbose, miglitol and voglibose are used. These inhibit degradation of carbohydrates thereby reducing the glucose absorption by the cells. To enhance glucose uptake by peripheral cells biguanide such as metphormine is used. Sulphonylureas like glibenclamide is insulinotropic and works as secretogogue for pancreatic cells. Although several therapies are in use for treatment, there are certain limitations due to high cost and side effects such as development of hypoglycemia, weight gain, gastrointestinal disturbances, liver toxicity etc [14]. Based on recent advances and involvement of oxidative stress in complicating diabetes mellitus, efforts are on to find suitable antidiabetic and antioxidant therapy.

Medicinal plants are being looked up once again for the treatment of diabetes. Many conventional drugs have been derived from prototypic molecules in medicinal plants. Metformin exemplifies an efficacious oral glucose-lowering agent. Its development was based on the use of Galega officinalis to treat diabetes. Galega officinalis is rich in guanidine, the hypoglycemic component. Because guanidine is too toxic for clinical use, the alkyl biguanides synthalin A and synthalin B were introduced as oral anti-diabetic agents in Europe in the 1920s but were discontinued after insulin became more widely available. However, experience with guanidine and biguanides prompted the development of metformin. To date, over 400 traditional plant treatments for diabetes have been reported, although only a small number of these have received scientific and medical evaluation to assess their efficacy. The hypoglycemic effect of some herbal extracts has been confirmed in human and animal models of type 2 diabetes. The World Health Organization Expert Committee on diabetes has recommended that traditional medicinal herbs be further investigated.