Investigation of traditional Australian Aboriginal and Indian Ayurvedic medicinal plants for their role in management of type 2 diabetes

Diabetes mellitus is not a single disease but is a group of metabolic diseases affecting a large number of people globally. It is mainly characterized by hyperglycemia due to in-sufficient production of insulin. Plants have been the main source of medicines since ancient times and are the richest source of natural compounds. Plants continue to pro-vide new chemical entities for the development of drugs against various diseases like cancer, diabetes, inflammation, hypertension and neurodegeneration. In this project, the bioactivity of extracts of seven Australian Aboriginal and nineteen Indian Ayurvedic plants were studied. The main aim of the project was to evaluate these plant extracts for their potential to help in the management of type 2 diabetes and related complications. Antimicrobial screening of the plant extracts revealed that the Australian Aboriginal extracts were active against only Gram-positive bacteria whereas Indian Ayurvedic ex-tracts showed a broad spectrum of activity against Gram-positive and Gram-negative bacteria. The antioxidant activity of Acacia ligulata was found to be strongest with an IC50 of 6.98 μg/ml against DPPH. Acacia kempeana showed strongest activity against ABTS with IC50 of 8.86 μg/ml. Among the Indian plant extracts, Bacopa moneirrei and Andrographis paniculata showed good free radical scavenging activity with IC50 of 14.95 μg/ml each in the DPPH assay and 23.56 μg/ml and 41.65 μg/ml, respectively, in the ABTS assay. Cytotoxicity studies revealed that Acacia kempeana and Acacia tetragonophylla were found to have good activity against HeLa cancer cells, suggesting their potential use as anti-cancer agents. The main focus of the study was to investigate the ability of the plant extracts to inhibit enzymes responsible for carbohydrate digestion (thus controlling hyperglycemia), specifically alpha-amylase and alpha-glucosidase. Extracts of Santalum spicatum (IC50 5.43 μg/ml), Chlorophytum borivilianum (IC50 4.17 μg/ml), Plumbago zeylenica (IC50 4.36 μg/ml), Solanum nigrum (IC50 4.87 μg/ml) and Pterocarpus marsupium (IC50 6.98 μg/ml) were particularly active against alpha-amylase enzyme, while Beyeria leshnaultii (IC50 0.48 μg/ml), Chlorophytum borivilianum (IC50 0.58 μg/ml) and Mucuna pruriens (IC50 0.80 μg/ml) showed potent activity against -glucosidase enzyme. The IC50 value was compared with positive control acarbose. The same plant extracts were also screened against angiotensin converting enzyme (ACE-I) and the results were compared with the positive control, captopril, however none of the extracts were found be compa-rable with captopril against this enzyme. Twelve plant extracts were selected and further evaluated for their antidiabetic activity against murine adipocytes to investigate glucose uptake and adipogenesis in cultured cells i.e. 3T3-L1 adipocytes. At 100 μg/ml, Acacia kempeana and Curculigo orchioides enhanced basal glucose uptake into differentiated 3T3-L1 cells by 19 % and enhanced insulin-stimulated uptake by 45 % and 48 %, respectively. The plants were compared to the positive control, rosiglitazone. Among the plant extracts examined, Acacia tetragonophylla reduced lipid accumulation by 82 % whereas Beyeria leshnaultii, Eu-phorbia drummondii and Curculigo orchioides were found to significantly reduce lipid accumulation by 73 %, 65 % and 31 %, respectively, in 3T3-L1 adipocytes, thus found to be helpful in reducing adipogenesis. The Australian Aboriginal plants have been tra-ditionally used for general illnesses but have no documented use for diabetes, thus this is the first study to report their potential use in the management of type 2 diabetes. The plants showing potent activity may be developed into novel and safe treatments for type 2 diabetes and related complications.