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Activation of estrogen receptor α (ERα) is required for Alisol B23-acetate to prevent post-menopausal atherosclerosis and reduced lipid accumulation.

Abstract：

:The risk of atherosclerosis (AS) ascends among post-menopausal women, while current hormone replacement therapy exerts several adverse effects. Alisol B 23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, was reported to show multiple physiological activities, including regulating lipid metabolism. According to molecular docking analysis, it was predicted to bind with estrogen receptor α (ERα). In this study, we aimed to observe the effect of AB23A on preventing post-menopausal AS and explore whether the mechanism was mediated by ERα. In vitro, free fatty acid (FFA) was applied to induce the abnormal lipid metabolism of L02 cells. In vivo, the ApoE-/- mice were ovariectomized to mimic the cessation of estrogen. The high-fat diet was also given to induce post-menopausal AS. We demonstrated AB23A attenuated the accumulation of total cholesterol and triglyceride induced by free fatty acids in hepatocytes. In high-fat diet-ovariectomy-treated ApoE-/- mice, AB23A eliminated lipids in blood and liver. AB23A not only reduced the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) through sterol-regulatory element binding proteins (SREBPs) but also suppressed the secretion of PCSK9 through silent information regulator 1 (SIRT1). Notably, AB23A promoted the expression of ERα in vivo and in vitro. The both ERα inhibitor and ERα siRNA were also applied in confirming whether the hepatic protective effect of AB23A was mediated by ERα. We found that AB23A significantly promoted the expression of ERα. AB23A could inhibit the synthesis and secretion of PCSK9 through ERα, lower the accumulation of triglyceride and cholesterol, and prevent post-menopausal AS.

journal_name

Life Sci

journal_title

Life sciences

authors

Chen Q,Chao Y,Zhang W,Zhang Y,Bi Y,Fu Y,Cai D,Meng Q,Li Y,Bian H

doi

10.1016/j.lfs.2020.118030

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

118030

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(20)30780-3

journal_volume

258

pub_type

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Activation of estrogen receptor α (ERα) is required for Alisol B23-acetate to prevent post-menopausal atherosclerosis and reduced lipid accumulation.