Therapeutic efficacy of catharanthus roseus in type 1 and type 2 diabetes mellitus in wistar rats

Abstract

This study was undertaken to systematically investigate the beneficial effects of Catharanthus roseus (C. roseus) in insulin-deficient and insulin-resistant conditions. Type 1 diabetes is a metabolic disorder due to insulin deficiency whereas insulin resistance is the prominent feature of Type 2, both types of diabetes are characterized by hyperglycemia. Chronic hyperglycemia by itself and by its associated oxidative stress plays an important role in the initiation and progression of diabetic complications. Due to increasing obesity, altered dietary habits and sedentary life style both in western and developing countries, the prevalence of both types of diabetes are growing at an exponential rate. In conventional therapy, Type 1 diabetes is treated with exogenous insulin and Type 2 with oral hypoglycemic agents (sulfonylureas, biguanides, etc.). In modern medicine, no satisfactory effective therapy is available to cure Diabetes Mellitus (DM). Though insulin therapy is used for management of DM, there are several drawbacks like insulin resistance, anorexia nervosa, brain atrophy, and fatty liver after chronic treatment. Unfortunately, apart from having a number of side effects, none of the oral hypoglycemic agents have been successful in maintaining euglyce- mia and controlling long-term microvascular and macrovascular complications. Moreover, these therapies only partially compensate for metabolic derangements seen in diabetes and do not necessarily correct the fundamental biochemical lesions. The yawning gap for additional agents to combat hyperglycemia and its accompanying complications presents an opening to revisit traditional antidiabetic plants. Many traditional plant treatments for diabetes exist. However, few have received scientific or medical scrutiny, and the World Health Organization has recommended that traditional plant treatments for diabetes warrant further evaluation. C. roseus, belongs to family Apocynaceae, is a subshrub also known as Madagascar periwinkle, Vinca rosea, or Lanchnera rosea worldwide. The plant C. roseus has gained acceptance from the pharmaceutical industries as it is widely used as an infusion in different parts of world to treat diabetes. Results from animal studies support the claim that this plant shows antihyperglycemic and hypolipidemic activity. Although earlier reports indicate blood glucose lowering activity in alcoholic extracts of leaves, no information is available on the biochemical basis related to antidiabetic property of C. roseus. The present study revealed the biochemical basis for the antidiabetic activity of C. roseus in streptozotocin-induced Type 1 DM and high fructose diet-induced insulin-resistant Type 2 diabetic rat models. In this study, a total of 48 male Wistar rats, aged 6-7 weeks were used. One-third of the experimental animals were made diabetic by a single intraperitoneal injection of freshly prepared Streptozotocin (STZ) (55 mg/kg body weight, in ice-cold 0.1 M citrate buffer, pH 4.5, in a volume of 0.1 mL per rat). Insulin resistance was induced in another one-third of experimental animals by feeding fructose-enriched diet (containing 66% fructose, 18% protein, 8% fat, 4% cellulose, 3% mineral and 1% vitamin mix). The remaining one-third of animals served as control and maintained on standard pellet diet. The rats were divided into six groups-control group (C-group), control rats treated with C. roseus (C + CR), STZ diabetic group (D-group), diabetic animals treated with C. roseus (D + CR), fructose-fed rats (Group-F), fructose-fed rats coadministered with C. roseus (F + CR). Treatment with C. roseus to both STZ-induced Type 1 and fructose diet-induced Type 2 rats for 60 days, rectified the alterations in the activities of key enzymes of glycolytic, gluconeogenesis and polyol pathway, and intestinal disaccharides. Further, accumulation of lipids in hepatic and cardiac tissues, and enhanced oxidative stress in liver, pancreas, kidney, and heart tissues were brought to near-normal values in both the groups after treatment with C. roseus. The multiple beneficiary properties like antidiabetic, hpolipidemic, insulin sensitizing activities of C. Roseus along with antioxidant potential offers an exciting opportunity to develop a novel and safe therapeutic approach for both Type 1 and Type 2 diabetes.