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

Abstract

Alismatis 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 PPARa and PPARd proteins in HepG2 cells and in liver tissue from ApoE −/− mice. Alisol A activated the AMPK/SIRT1 signaling pathway and NF-kB inhibitor IkBa 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.

Alisol A attenuates malignant phenotypes of colorectal cancer cells by inactivating PI3K/Akt signaling

“…For example, Alisol A represses metabolic disorders and high-fat diet-related obesity via AMPK/ACC/SREBP-1c signaling ( 26 ). Alisol A relieves arterial plaque in an apoE-knockout mouse model by enhancing AMPK-SIRT1 signaling ( 14 ). Alisol A inhibits invasion, migration and proliferation of breast cancer cells ( 27 ).…”

“…Alismatis rhizoma contains several active chemical constituents, including essential oils, diterpenes, sesquiterpenes, polysaccharides and triterpenoids ( 13 ). Alisol A serves as a tetracyclic protostane-type triterpenoid and a major component of Alismatis rhizoma ( 14 ). A study has identified the antitumor effect of Alisol A on breast cancer cells ( 15 ), but the function of Alisol A in colorectal cancer development remains unknown.…”

Pharmacological Properties and Molecular Targets of Alisol Triterpenoids from Alismatis Rhizoma

“…A distinct mechanism has been invoked to explain the anti-atherosclerotic activity of Ali-A. In this case, the compound activated the AMPK/SIRT1 signaling pathway, thereby inhibiting the formation of arterial plaques to block the progression of atherosclerosis [ 68 ]. A molecular docking study suggested that Ali-A could bind selectively to the catalytic region of AMPK, and, as such, the compound could activate the AMPK/acetyl-CoA carboxylase/SREBP-1c pathway, leading to reduced hepatic steatosis and improved liver function in a model of obese mice [ 69 , 70 ].…”

Multi-Omics Integration Analysis Identifies Lipid Disorder of a Non-Alcoholic Fatty Liver Disease (NAFLD) Mouse Model Improved by Zexie–Baizhu Decoction

“…Many extracts and some bioactive monomers of zexie and baizhu have been discovered to ameliorate metabolic diseases, especially lipid metabolism disorders. For instance, alisol A/alisol B/alisol-2,3-C from Zexie and atractylenolides (I, II, and III) from Baizhu can improve lipid metabolism via activating PI3K/Akt, AMPK, and JAK-STAT pathways ( Chen et al, 2020 ; Wang et al, 2020 ; Yu et al, 2020 ; Sun et al, 2021a ; Deng et al, 2021 ; Luan et al, 2021 ). Several kinds of alcohol extracts of zexie were also reported to benefit the lipid metabolism and relieve inflammation ( Park et al, 2014 ; Jang et al, 2015 ; Zhang et al, 2017 ; Liu et al, 2019 ), and several TCM formulas containing Zexie and Baizhu are effective for NAFLD in previous studies ( Fang et al, 2017 ; Feng et al, 2019a ; Cheng et al, 2019 ; Tang et al, 2020 ).…”