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.
Highlights
Cardiovascular disease is a big threat of human health worldwide
In order to explore the mechanisms of action of alisol A on AS, we evaluated the expression of PPARa, PPARd, and AMPK/SIRT1 pathway in the liver of ApoE−/− mice by immunoblotting
As alisol A is the main component of Alismatis Rhizoma (AR) extract, we assessed its effect on plasma lipid, aorta diameter and plaque formation in apoE-deficient mice fed with high-fat diet
Summary
Atherosclerosis (AS) is the pathological basis of coronary heart disease, myocardial infarction and ischemic stroke. It is characterized by the deposition of atheromatous plaques on the walls of blood vessels, leading to arterial stenosis (Lusis, 2000). Statins reduce liver cholesterol synthesis by inhibiting HMG-CoA reductase and decrease low-density lipoprotein cholesterol (LDL-C) levels in plasma (Ray et al, 2014). AS is a complex disease caused by the combination of a variety of factors, including excessive activation of macrophages, increased endothelial permeability, and chronic inflammation. The lipidlowering effect of statins has been clinically proven, it was found that statins reduce the incidence of atherosclerotic cardiovascular disease mainly by lowering LDL, and the reduction is only in one-third of patients (Tall, 2017). Satins cause some adverse effects such as myopathy, elevated
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