Cytoprotective effects of combination of gypenosides and Costus pictus D.Don extract in BRIN-BD11 β-cells

Ethnopharmacological RelevanceGypenosides and Costus pictus D.Don are used as an anti-diabetic herbal remedy in China and India respectively. However, the synergistic effect of these two extracts on {beta}-cell protection is not yet elucidated. IntroductionIn Type 2 diabetes mellitus (T2DM), pro-inflammatory cytokines and lipotoxicity are known causes of pancreatic {beta}-cell dysfunction and impaired insulin secretion and eventually {beta}-cell death. Thus, any cytoprotective drug supplements can protect the {beta}-cell and may help in T2DM treatment. Gypenosides, extracted from the Chinese medicinal herb Gynostemma pentaphyllum and the leaf extract from an Indian medicinal herb Costus pictus D. Don are used in traditional medicine due to their insulin secretory properties. In our previous studies, both extracts have shown significant cytoprotective effects in insulin-secreting BRIN-BD11 cells. In the present study, we aim to investigate the synergistic effects of a combination of these extracts on BRIN-BD11 {beta}-cell protection. MethodsCombination of extracts was prepared by adding Gypenosides with Costus pictus at 2:1 to a concentration of 18.75mg/ml. Cell viability was determined by MTT assay following treatment with combination and/or palmitate and cytokine cocktail for 24-48h. Following 24h treatment, proliferation was measured by Ki67 staining and cytoprotective gene expression was quantified by qPCR. ResultsCombination treatment of 25{micro}g/ml enhanced cell viability both at 24h (n=8; P<0.05) and 48h (n=8; P<0.0001) treatment. Over 24h, combination treatment (25&12.5 {micro}g/ml) showed a significant protective effect against 125{micro}M and 250{micro}M palmitate induced (P<0.0001) and cytokine cocktail-(TNF 1000U, IL-1{beta} 50U & IFN{gamma} 1000U) (P<0.0001 & P<0.01 respectively) induced toxicity. Combination treatment over 24h increased expression of antioxidant genes Nrf2 (P<0.001), Cat (P<0.001) and Sod1 (P<0.05) along with pro-proliferative Erk1 (P<0.01) while pro-inflammatory Nfkb1 expression was reduced(P<0.001). ConclusionThe results suggest that a combination of gypenosides and costus pictus may protect {beta}-cells against inflammatory cytokines and lipotoxicity caused by saturated free fatty acids associated with obesity and diabetes.