中药新药与临床药理2026，Vol.37Issue(5)：797-806,10.DOI:10.19378/j.issn.1003-9783.2026.05.003
丹酚酸C改善db/db小鼠脂质代谢紊乱的作用机制
Mechanism of Salvianolic Acid C in Improving Lipid Metabolism Disorder in db/db Mice
摘要
Abstract
Objective To investigate the effect and molecular mechanism of salvianolic acid C in improving lipid metabolism disorder in db/db mice by activating the PPARα signaling pathway.Methods C57BLKS/J(db/db)mice were randomly divided into 5 groups(n=10 per group):model group(db/db group),simvastatin group(positive control,10 mg·kg-1),and low-dose(5 mg·kg-1),medium-dose(10 mg·kg-1),and high-dose(20 mg·kg-1)salvianolic acid C groups.Additionally,10 littermate db/m mice were selected as the normal control group(db/m group).Mice in each administration group were given the corresponding drugs by gavage once daily for 8 consecutive weeks.Serum levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),as well as hepatic TC and TG contents,were measured.Hepatic lipid accumulation was observed using Oil Red O staining.Network pharmacology was employed to screen potential targets of salvianolic acid C for intervening in lipid metabolism disorder,followed by GO function annotation and KEGG pathway enrichment analysis.Western Blot was used to detect the protein expression levels of PPARα,CPT1-α,and PGC-1α in mouse liver.qPCR was used to detect the mRNA expression levels of PPARα,ACOX1,CPT1-α,PGC-1α,SREBP-1,ACC,FABP-1,ADIPOR,and ACO in mouse liver.A protein-protein interaction(PPI)network of potential targets of salvianolic acid C for lipid metabolism disorder was constructed to screen upstream core targets of the PPARα pathway,and molecular docking was performed to validate the binding of salvianolic acid C with these targets.Results(1)Animai experiment:Compared with the normal control group,the model group exhibited significantly increased serum levels of TC,TG,and LDL-C(P＜0.01),and significantly decreased HDL-C levels(P＜0.01).Marked hepatic lipid accumulation was observed,with a significant increase in the positive area of lipid droplets(P＜0.01)and significantly elevated hepatic TC and TG levels(P＜0.01).Hepatic protein levels of PARα,CPT1-α,and PGC-1α were significantly decreased(P＜0.05).The mRNA expression levels of PPARα,ACOX1,CPT1-α,PGC-1α,FABP-1,ADIPOR,and ACO,which are involved in fatty acid β-oxidation,transport,and mitochondrial transport processes,were significantly decreased(P＜0.01),while the mRNA expression levels of lipid synthesis-related SREBP-1 and ACC were significantly increased(P＜0.01).Compared with the model group,the medium-and high-dose salvianolic acid C groups showed significantly reduced serum TC,TG,and LDL-C levels(P＜0.05,P＜0.01),a significantly reduced positive area of hepatic lipid droplets(P＜0.05,P＜0.01),and significantly decreased hepatic TC and TG levels(P＜0.01).The mRNA expression levels of PPARα,CPT1-α,PGC-1α,FABP-1,and ACO were significantly upregulated(P＜0.01),while ACC mRNA expression was significantly downregulated(P＜0.01).In the high-dose salvianolic acid C group,hepatic protein expression levels of PPARα,CPT1-α,and PGC-1α were significantly increased(P＜0.01),ACOX1,ADIPOR mRNA expression was significantly upregulated(P＜0.01),and SREBP-1 mRNA expression was significantly downregulated(P＜0.01).(2)Network pharamacology:A total of 75 potential targets of salvianolic acid C for intervening in lipid metabolism disorder were identified,which were primarily involved in lipid metabolism-related biological processes such as fatty acid metabolism and steroid metabolism.The PPAR signaling pathway emerged as one of the key pathways through which salvianolic acid C may regulate lipid metabolism.Thirty core targets were screened,and salvianolic acid C was shown to stably bind to the key upstream regulatory protein targets of the PPARα pathway,FASN,NR3C1,and RXRA,with binding energies of-10.2,-8.4,and-8.9 kcal·mol-1,respectively.Conclusion Salvianolic acid C ameliorates lipid metabolism disorder in db/db mice by activating the PPARα signaling pathway,upregulating the expression of its key downstream factors such as CPT1-αand PGC-1α,thereby promoting fatty acid β-oxidation and energy metabolism,and inhibiting hepatic lipid accumulation.关键词
丹酚酸C/高脂血症/脂质代谢紊乱/脂质蓄积/PPARα通路/db/db小鼠/网络药理学/分子对接Key words
salvianolic acid C/hyperlipidemia/lipid metabolism disorder/lipid accumulation/PPARα pathway/db/db mice/network pharmacology/molecular docking分类
医药卫生引用本文复制引用
吕明真,张效威,石贤聪,高改,段亚飞,高艳杰,唐智利,张振强,徐江雁,谢治深..丹酚酸C改善db/db小鼠脂质代谢紊乱的作用机制[J].中药新药与临床药理,2026,37(5):797-806,10.基金项目
国家自然科学基金项目(82474495,82174267) （82474495,82174267）
河南省高校科技创新人才支持项目(24HASTIT072) （24HASTIT072）
河南省中医药科研专项课题(2023ZYZD15) （2023ZYZD15）
河南省高等学校大学生创新训练计划项目(202410471014). （202410471014）
