On August 31, 2022, Ma, Xiaoyao; Bai, Yongping; Liu, Kaixin; Han, Yiman; Zhang, Jinling; Liu, Yuteng; Hou, Xiaotao; Hao, Erwei; Hou, Yuanyuan; Bai, Gang published an article.HPLC of Formula: 473-81-4 The title of the article was Ursolic acid inhibits the cholesterol biosynthesis and alleviates high fat diet-induced hypercholesterolemia via irreversible inhibition of HMGCS1 in vivo. And the article contained the following:
In hypercholesteremia, the concentrations of total cholesterol (TC) and low-d. lipoprotein cholesterol (LDL-C) are enhanced in serum, which is strongly associated with an increased risk of developing atherosclerosis. Ursolic acid (UA), a pentacyclic terpenoid carboxylic acid, was found to alleviate hypercholesterolemia and hypercholesterolemia-induced cardiovascular disease. However, the specific targets and mol. mechanisms related to the effects of UA in reducing cholesterol have not been elucidated. In this study, we aimed to illustrate the target of UA in the treatment of hypercholesterolemia and to reveal its underlying mol. mechanism. Nontargeted metabolomics was conducted to analyze the metabolites and related pathways that UA affected in vivo. The main lipid metabolism targets of UA were analyzed by target fishing and fluorescence colocalization in mouse liver. Mol. docking, in-gel fluorescence scan and thermal shift were assessed to further investigate the binding site of the UA metabolite with HMGCS1. C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk to induce hypercholesteremia. Liver tissues were used to verify the cholesterol-lowering mol. mechanism of UA by targeted metabolomics, serum was used to detect biochem. indexes, and the entire aorta was used to analyze the formation of atherosclerotic lesions. Our results showed that hydroxy-3-methylglutaryl CoA synthetase 1 (HMGCS1) was the primary lipid metabolism target protein of UA. The UA metabolite epoxy-modified UA irreversibly bonds with the thiol of Cys-129 in HMGCS1, which inhibits the catalytic activity of HMGCS1 and reduces the generation of precursors in cholesterol biosynthesis in vivo. The contents of TC and LDL-C in serum and the formation of the atherosclerotic area in the entire aorta were markedly reduced with UA treatment in Diet-induced hypercholesteremia mice. UA inhibits the catalytic activity of HMGCS1, reduces the generation of downstream metabolites in the process of cholesterol biosynthesis and alleviates Diet-induced hypercholesteremia via irreversible binding with HMGCS1 in vivo. It is the first time to clarify the irreversible inhibition mechanism of UA against HMGCS1. This paper provides an increased understanding of UA, particularly regarding the mol. mechanism of the cholesterol-lowering effect, and demonstrates the potential of UA as a novel therapeutic for the treatment of hypercholesteremia. The experimental process involved the reaction of 2,3-Dihydroxypropanoic acid(cas: 473-81-4).HPLC of Formula: 473-81-4
The Article related to ursolic acid anticholesteremic hmgcs1 cholesterol biosynthesis hypercholesterolemia, cholesterol biosynthesis, covalent binding, hmgcs1, hypercholesteremia, metabolite, ursolic acid and other aspects.HPLC of Formula: 473-81-4
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