Summary

Diabetes mellitus and dyslipidemia are among the fastest growing global health issues in the 21st century. People living with diabetes are at a higher risk of developing a number of serious and life-threatening complications, leading to an increased need for medical care, a reduced quality of life, and undue stress on families. Diabetes and its complications, if not well managed, can lead to frequent hospital admissions and premature death. Globally, diabetes is among the top 10 causes of death. According to the IDF data, in 2019, it is estimated that 463 million people have diabetes and this number is projected to reach 578 million by 2030, and 700 million by 2045. Two-thirds of people with diabetes live in urban areas and three of four are of working age. Over four million people aged 20–79 years were estimated to die from diabetes-related causes in 2019. However, it was found that diabetes can be well managed and its complications can be prevented with early diagnosis and access to appropriate care. Furthermore, type 2 diabetes mellitus can often be prevented and there is compelling evidence to suggest it can be reversed in some cases. The purpose of the proposed research study is to develop an alternative way of supporting the management of type 2 diabetes and its complication while developing preventive protocol to reduce prevalence of diabetes and dyslipidaemia. The proposed research is consisted of three work packages and overall result would be the preventive and curative protocol for the management of diabetes mellitus and dyslipidaemia.

Previous studies done by our research team have identified the possible alternative drug lead from the hot water extract of the polyherbal composition made of leaves of Murraya koenigii (L.) Spreng., cloves of Allium sativum L., seeds of Piper nigrum L.and fruits of Garcinia quaesita, Pierre, which exerted significant antihyperglycaemic and antihyperlipideamic activities in diabetic rats through improved β-cell functions in the pancreas. Further it showed a significant increase in HDL-C and decrease in LDL-C levels as well. Work package one will be focused on the developing a standardized product which then use in human trials on individuals with prediabetes and diabetic patients in order to identify the efficacy, toxicity and feasibility of aforementioned drug formulae. This study would result capsule development as an alternative, inexpensive, curative plan with no toxic effects for the management of type 2 diabetes and its complications, that could reduce the burden of management of these diseases.

In addition, current studies revealed that combined drug therapy where combination of another drug with the main active drug can be used to treat diabetics as well as hyperlipidaemic patients by achieving target glucose and LDL-C levels. However, difficulties in finding a correct combination of drugs and increased cost are major drawbacks of this strategy and warrant the identification of new compounds that have synergistically active effects on these diseases. Hence our work package two will be focused on identification of the correct combination of active pharmaceuticals present in the aforementioned polyherbal composition, as well as their antidiabetic mechanisms. Identification of the correct combination of bioactive compounds, along with their mechanistic understanding, will produce combined therapeutic drug leads which have the potential to be a therapeutic drug, would produce patentable results, new research collaboration with international pharmaceutical industries as well as bring the attention of foreign investors.

Work package three will be focused on investigation of the preventive ability or the protective effects of the polyherbal mixture against diabetes mellitus in obese Wistar rat model. Identification of the protective ability of the aforementioned polyherbal composition could result another user friendly, inexpensive nutraceutical product which could help whole society as a preventive method. Overall, many Sci index publications, patents, human resource development by training three post graduate students with sound knowledge and experience in several disciplines as Natural product chemistry, Pharmacognosy and Biochemistry, infrastructure development at the research laboratories in two national universities, industry university interactions as well as socio economic developments would be among the several expected outcomes from the proposed research program.

Objectives

• Standardize a polyherbal composition containing freeze dried powder of leaves of Murraya koenigii, cloves of Allium sativum, seeds of Piper nigrum and fruits of Garcinia quaesita using standard analytical methods
• Determine stability, shelf life and pharmacokinetic properties of the polyherbal composition
• Determine the proximate nutrient composition of the polyherbal mixture
• Determine the antihyperglycaemic effect of the polyherbal composition in patients with type 2 diabetes mellitus
• Determine adverse/toxic effects of the polyherbal composition in above study subjects
• Investigate the effect of the polyherbal composition on oxidative stress markers and inflammatory markers, hyperlipidaemia in patients with type 2 diabetes mellitus
• Identify antidiabetic secondary metabolites of the polyherbal composition using bioassay guided principle
• Develop structure activity relationships using synthetic modifications to the identified compounds
• Investigate advanced cellular antidiabetic mechanisms of the isolated compounds in high fat streptozotocin induced type 2 diabetic rats
• Investigate the protective effects of the polyherbal mixture against diabetes mellitus in obese Wistar rat model
• Seek possibilities for the commercialization of the polyherbal composition

Major Equipment Facilitated by Grant

• High Performance Liquid Chromatograph with UV detector, FID, autosampler, and mass detector
• Freeze Dryer
• Rotatory evaporators (2)
• Microplate reader
• Microscope with image facility

Designation

Principal Investigator (PI)

Deputy Principal Investigator (DPI)

Co- investigator

Co- investigator

Co- investigator

Co- investigator

Institute

University of Peradeniya

University of Ruhuna

Teaching Hospital, Kandy

Industrial Technology Institution

University of Peradeniya

Sirimavo Bandaranayake: specialized children hospital