A novel pentacyclic triterpenoid, Ilexgenin A, shows reduction of atherosclerosis in apolipoprotein E deficient mice

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Ilexgenin A (IA), a novel pentacyclic triterpenoid, is a compound extracted from leaves of Ilex hainanensis Merr. In this study, we explored the efficacy of IA on atherosclerosis and its underlying mechanism. We determined that treatment with IA attenuated atherosclerosis in high-fat diet-induced apolipoprotein E deficient mice via a series of effects involving regulation of lipid parameters, decrease of atherosclerosis-related indexes, inhibition of inflammatory cytokines secretion and pathological changes of main organs. Furthermore, the underlying mechanism of IA was investigated on oxidized low-density lipoprotein (Ox-LDL)-induced THP-1 cells. We showed that pre-treatment with IA decreased active inflammation cytokines involving interleukin-6 (IL-6), IL-1 and tumor necrosis factor-α (TNF-α) expression in a concentration-dependent manner. In addition, we confirmed that IA inhibited the phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), IKKα phosphorylation and NF-κB activity induced by Ox-LDL. Overall, these findings define IA as a novel drug candidate for anti-atherosclerotic therapy.HighlightsIA has potential lipid-lowering effects in high-fat diet induced apo E deficient mice.IA inhibits inflammation cytokine expressions in high-fat diet induced apo E deficient mice.IA inhibits phosphorylation of PI3K/Akt/IKKα in Ox-LDL-induced THP-1 cells.IA inhibits inflammation cytokine expressions in Ox-LDL-induced THP-1 cells.

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