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

  • Front Pharmacol. 2020 Nov 2:11:580073. doi: 10.3389/fphar.2020.580073.
Ke Wang  1 Beibei Zhang  1 Dingzhong Song  1 Jianqiang Xi  1 Wusi Hao  1 Jie Yuan  1 Chenyu Gao  1 Zhongbao Cui  1 Zhihong Cheng  1
Affiliations
  • 1. China State Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, Shanghai, China.
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.

Keywords
AMPK/SIRT1 pathway; Alisol A; PPARα/δ; anti-atherogenesis; anti-inflammation.
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