Summary

Type 2 diabetes mellitus (T2DM) is considered as one of the emerging global health problems because of its increasing prevalence, adverse clinical outcomes, marked reduction in the quality of life of patients and high healthcare costs. Sri Lanka has also witnessed an alarmingly high prevalence of T2DM during the past ten years. With several draw backs of modern pharmaceutical agents, high health care costs in the management of T2DM and related complications have led to research on novel antidiabetic agents, targeting diverse pathological conditions of T2DM. Healing with medicinal plants is as old as mankind itself. It is being appreciated that traditional systems of medicine offer some effective medicinal plant preparations from their treatise to be useful in the treatment of T2DM. Coccinia grandis (Linn.) Voigt (Cucurbitaceae) is an edible perennial climber commonly found in Sri Lanka and in tropical Asia. The antidiabetic potency of the leaf extract C. grandis is well documented in literature. Thus, extensive research on antidiabetic potential of aqueous leaf extract of C. grnadis has been carried out by our research group previously. The proposed study is aimed to develop a standardized, value added herbal antidiabetic agent with proven clinical efficacy and to identify antidiabetic compound(s)/ drug lead compounds for the management of T2DM. First a herbal drug of C. grandis will be developed using the freeze dried form of the plant material and will be standardized according to the standard protocols. In addition, proximate nutritional composition will be determined. Then, a randomized double-blind placebo control clinical trial of the herbal product of C. grandis will be carried out in newly diagnosed patients with T2DM. The effect of the herbal drug on hyperglycaemia, dyslipidaemia, oxidative stress and inflammation will be assessed by selected biomarkers. Then the identification of the active extracts will be carried out using selected in vitro antidiabetic assays; α-amylase inhibition assay, α-glucosidase inhibition assay and DPP-4 inhibition assay.

The most active extract/s will be selected, further separated by bioassay guided fractionation and active antidiabetic compounds will be isolated. Then the structures of isolated antidiabetic compound/s will be elucidated by the application of spectroscopic techniques.The development of antidiabetic agent/neutraceutical will have the potential to manage T2DM at the onset/primary stage, slow down the progression of diabetic complications and delay the need of complex treatment options to maximum possible extent. In addition, positive results of the study will complement the efforts in reaching the global health needs of general public and enhance the quality of life of patients. The project will also help to develop skills and knowledge of a young scientist and award of a post graduate research degree.

Objectives

1. Main objective:

   To determine the clinical efficacy and safety of the herbal drug of Coccinia grandis and to isolate antidiabetic compounds from the leaf extract of Coccinia grandis of Sri Lankan origin

2. Specific objectives:

   1. To standardize a herbal drug containing freeze dried powder of C. grandis using standard analytical methods
   2. To determine the nutritional profile of the herbal drug mentioned in objective 1
   3. To determine the effect of herbal drug of C. grandis on hyperglycaemia, oxidative stress and inflammation in patients with type 2 diabetes mellitus
   4. To isolate antidiabetc compounds from the active fraction(s) of C. grandis by bioassay guided fractionation

Major Equipment Facilitated by Grant