Alisol A Alleviates Arterial Plaque by Activating AMPK/SIRT1 Signaling Pathway in apoE-Deficient Mice.

ABSTRACT

A lismatis Rhizoma (zexie), an herb used in traditional Chinese medicine, exhibits hypolipemic, anti-inflammation and anti-atherosclerotic activities. Alisol A is one of the main active ingredients in Alismatis Rhizoma extract. In this study, we investigate the role of alisol A in anti-atherosclerosis (AS). Our study demonstrated that alisol A can effectively inhibit the formation of arterial plaques and blocked the progression of AS in ApoE-/- mice fed with high-fat diet and significantly reduced the expression of inflammatory cytokins in aorta, including ICAM-1, IL-6, and MMP-9. In addition, we found that alisol A increased the expression of PPARα and PPARδ proteins in HepG2 cells and in liver tissue from ApoE-/- mice. Alisol A activated the AMPK/SIRT1 signaling pathway and NF-κB inhibitor IκBα in HepG2 cells. Our results suggested that alisol A is a multi-targeted agent that exerts anti-atherosclerotic action by regulating lipid metabolism and inhibiting inflammatory cytokine production. Therefore, alisol could be a promising lead compound to develop drugs for the treatment of AS.