Metabolic Bioactivity of Athrixia phylicoides

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University of Zululand
BACKGROUND: Insulin resistance is a major risk factor for the development of type 2 diabetes (T2D). It is characterized by insufficient response to secreted insulin in target tissues. In vitro studies demonstrated the ability of an aqueous extract of Athrixia phylicoides to increase glucose uptake and utilization in myocytes, adipocytes and in Chang cells. It is therefore likely that this extract could also modulate glucose metabolism in insulin-resistant cells. This study investigated the effect of an aqueous A. phylicoides extract on glucose metabolism in differentiated, insulin-resistant C2C12 myocytes, C3A liver cells, 3T3-L1 adipocytes and in diabetic db/db mice. METHODS: Insulin resistance was induced in vitro using palmitic acid (750μM) for 16 hours followed by treatment with two concentrations (10 and 100 μg/ml) of the extract, in the presence and absence of insulin, for 3 hours. Glucose uptake was assessed by 2-deoxy-[3H]-D-glucose uptake. Western blot analysis of proteins involved in insulin dependent (AKT) and insulin independent (AMPK) glucose uptake were investigated. The inhibitory effect of A. phylicoides on PTP1B enzyme activity was also assessed. Six-week old obese C57BLKS db/db mice were treated with A. phylicoides extract (20 and 200 mg/kg body weight) in the diet for 30 days. Body weights, fasting blood glucose levels, food and water intake were monitored weekly followed by an oral glucose tolerance test and serum lipids assessment. The degree of steatosis was assessed in liver sections. RESULTS: Results suggested that A. phylicoides increased glucose uptake as well as AMPK phosphorylation in insulin-resistant C2C12 myocytes but had no effect on insulin resistance in C3A liver cells and 3T3-L1 adipocytes. In db/db mice, the A. phylicoides extract had no effect on body weight, fasting blood glucose or oral glucose tolerance. However, serum triglyceride content was markedly reduced with the lowest dose while the high dose markedly reduced the steatosis score in the liver sections. CONCLUSION: A. phylicoides extract was able to improve insulin stimulated glucose uptake in insulin-resistant C2C12 myocytes through AMPK dependent pathways. The extract is a potential inhibitor of PTP1B enzyme. While A. phylicoides had no effect on hyperglycemia and insulin resistance under the current experimental conditions, the effect on lipid metabolism should be further investigated.
A dissertation submitted to the Faculty of Science and Agriculture in fulfilment of the requirements for the Degree of Masters in Biochemistry in the Department of Biochemistry and Microbiology at the University Of Zululand, 2017
matabolism --athrixia phylicoides