Kuwanon G attenuates atherosclerosis by upregulation of LXRα-ABCA1/ABCG1 and inhibition of NFκB activity in macrophages

Abstract

BackgroundAtherosclerosis is characterized by chronic inflammation in vascular wall. Previous studies suggest that Kuwanon G (KWG) exerts anti-inflammatory activities. However, the effect of KWG on atherosclerosis remains unexplored. AimsTo explore whether KWG affects macrophage foam cell formation in vitro and atherogenesis in vivo. MethodsRAW 264.7 macrophages were stimulated with ox-LDL for 24h to induce foam cell formation and treated with KWG. Foam cell formation was determined by ORO staining and enzymatic analysis. Pro-inflammatory cytokines mRNA levels were tested by Real-time PCR method. Further molecular mechanism was investigated using Western blot. In vivo, ApoE−/− mice were fed with high-fat diet and intraperitoneally injected with KWG. Atherosclerotic lesion was accessed by H&E and ORO staining. Plaque composition was evaluated by immunohistochemistry and Sirius Red staining. Serum lipid profile and inflammatory cytokines were evaluated by enzymatic method and ELISA. ResultsKWG significantly decreased intracellular lipid accumulation and inflammatory cytokines mRNA levels in macrophages through enhancing LXRα-ABCA1/ABCG1 pathway and inhibiting NFκB activation. Administrated with KWG remarkably reduced the atherosclerotic lesion areas and macrophage content in the plaque of high-fat diet fed ApoE−/− mice. KWG also reduced hyperlipidemia and serum inflammatory cytokines in vivo. ConclusionTaken together, these data highlight that KWG can attenuate atherosclerosis through inhibiting foam cell formation and inflammatory response.