文献类型：期刊文献

英文题名：Molecular hybridization method for obtaining paeonol-based fibrate derivatives with potent lipid-lowering and hepatoprotective activity

作者：Quan, Lina[1];Guo, Ying[1];Wang, Siyao[1];Sun, Mengfei[1];Pang, Yan[1];Cui, Chunli[1];Wang, Jinrui[2];Wei, Jinlian[3];Wei, Peifeng[1,4];Xie, Yundong[1]

机构：[1]Shaanxi Univ Chinese Med, Coll Pharm, Xianyang New Ec Zone, Xian 79046, Peoples R China;[2]Northwest Univ, Coll Life Sci, Dept Life Sci & Med, Xian 710069, Peoples R China;[3]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[4]Shaanxi Univ Tradit Chinese Med, Affiliated Hosp 2, Xianyang, Peoples R China

年份：2024

卷号：33

期号：5

起止页码：796

外文期刊名：MEDICINAL CHEMISTRY RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001214777900001)】；

基金：This study was supported by Shaanxi University of Traditional Chinese Medicine Student Innovation and Entrepreneurship Training Program Project (No. 202210716107). Sci-Tech Innovation Talent System Construction Program of Shaanxi University of Chinese Medicine (No. 2023-CXTD-05). Shaanxi Special Support Plan Talent Project. Shaanxi Provincial Administration of Traditional Chinese Medicine "Double Chain Integration" Young and middle-aged Scientific Research and Innovation Team Project (No. 2022-SLRH-YQ-008). Shaanxi Province key research and development plan project (No. 2024SF-YBXM-496).

语种：英文

外文关键词：Paeonol-based fibrate derivatives; Hypolipidemia; Hepatoprotection; PPAR-alpha; HMG-CoA

摘要：Molecular hybridization method was applied to design and synthesize a series of target compounds paeonol-based fibrate derivatives. The target compound was screened using a Triton WR-1339 induced hyperlipidemia mouse model, and compound T9 was found to have good lipid-lowering activity. The dose-dependent study of its lipid-lowering activity was also conducted. To further evaluate the lipid-lowering activity of compound T9, a hyperlipidemic mouse model induced by high fat emulsion can be used. The findings of the research illustrate that T9 is capable of significantly decreasing blood lipid levels, including TG, TC, LDL-C, and increasing HDL-C. The results of liver tissue oil red O staining and HE staining demonstrated that T9 improved the hepatic lipid accumulation, thus decreasing AST and ALT levels and protecting against hyperlipidemic liver injury. Studies into the lipid-lowering effect of T9 have indicated that it can upregulate PPAR-alpha protein expression in liver tissue, while simultaneously decreasing the expression of HMG-CoA protein. T9 was further demonstrated to possess antioxidant properties, as evidenced by an increase in SOD and a decrease in MDA, as well as anti-inflammatory effects, demonstrated by a decrease in TNF-alpha, IL-1 beta, and IL-6, thus confirming its potential as a hypolipidemia and hepatoprotective agent.