Akebia Saponin D inhibits the formation of atherosclerosis in ApoE mice by attenuating oxidative stress-induced apoptosis in endothelial cells

Abstract Background and aims Akebia Saponin D (ASD) is a major bioactive triterpenoid saponin compound isolated from the Chinese herb Dipsacus asper wall (DSW). DSW has been long used as an anti-Alzheimer disease and anti-osteoporosis agent in clinics. However, anti-atherosclerotic effects of ASD have not been fully investigated. The objective of this study is to further investigate the anti-atherosclerotic activities and mechanisms of ASD in vivo and in vitro. Methods In in vitro experiments, ASD (50, 100, and 200 μM) was used to explore the effects of preventing H2O2-induced endothelial cell apoptosis and the possible mechanism involved. In in vivo experiments, ApoE−/− mice were fed a high fat diet (HFD) and treated with atorvastatin (10 mg/kg/d), ASD (50, 150, 450 mg/kg/d), or the combination therapy (atorvastatin 10 mg/kg/d and ASD 150 mg/kg/d) for 14 weeks. Results We found that ASD reduced the generation of reactive oxygen species, inhibited mitochondrial membrane potential (MMP) impairment, diminished the expression of Bax and Caspase-3, increased Bcl-2 expression, and inhibited apoptosis in endothelial cells. ASD significantly increased the expression of anti-oxidant enzymes (GSH, SOD, and CAT) in both liver and vascular tissue, reduced blood lipid levels (TG, TC, and LDL-C), and decreased lipid deposition in the liver and atherosclerotic lesion size in ApoE−/− mice. Conclusions Our study revealed that ASD inhibited atherosclerosis development in ApoE−/− mice by inhibiting oxidative stress-induced endothelial cell apoptosis signaling pathway, and suggested that ASD might be a potential therapeutic drug in the prevention of atherosclerosis.