Meng Xinyu, Chen Yan, Zhao Bingxian, Liu Qingpu, Zhao Liqin, Zheng Xiaoke, Feng Weisheng
College of Pharmacy, Henan University of Chinese Medicine, China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, China.
College of Pharmacy, Henan University of Chinese Medicine, China; The Engineering and Technology Research Center of Quality Control and Evaluation for Chinese Medicine Development of Henan Province, China.
Eur J Pharmacol. 2025 Jul 15;999:177701. doi: 10.1016/j.ejphar.2025.177701. Epub 2025 May 5.
Regulation of bile acid metabolism offers an effective approach of reducing hypercholesterolemia. Salvianolic acid B, a phenolic acid compound found in salvia miltiorrhiza Bge, has therapeutic effects on cardiovascular diseases. Nevertheless, insufficient is known concerning the impact on hypercholesterolemia. This study has investigated the cholesterol-lowering effect of salvianolic acid B and delved into its potential mechanism. Hypercholesterolemia mice model was induced by a high-cholesterol diet. We evaluated lipid parameters in serum and liver and examined pathology changes and gene expression alterations in liver. In addition, we examined the effect of salvianolic acid B on gut microbiota in colonic contents utilized 16S rRNA. Salvianolic acid B significantly decreased the levels of lipids in serum, improved lipid accumulation in liver, and significantly increased the feces bile acid content. RNA-seq analysis results showed that salvianolic acid B exerts a significant influence on primary bile acid biosynthesis. In addition, Salvianolic acid B enhanced the expression of cholesterol 7α-hydroxylase (CYP7A1) and sterol 27-hydroxylase(CYP27A1). Furthermore, salvianolic acid B inhibited the abundance of BSH-producing bacteria, and decreased the expression levels of farnesoid X receptor (FXR), fibroblast growth factor 15 (FGF-15), apical sodium-dependent bile acid transporter (ASBT) and ileum bile acid binding protein (I-BABP). Taken together, this study demonstrated that salvianolic acid B improved hypercholesterolemia by inhibiting the abundance of BSH-producing bacteria and ileum FXR/FGF-15 signaling to enhance the synthesis and excretion of bile acids.
调节胆汁酸代谢为降低高胆固醇血症提供了一种有效方法。丹酚酸B是一种存在于丹参中的酚酸化合物，对心血管疾病具有治疗作用。然而，关于其对高胆固醇血症的影响，人们了解得还不够充分。本研究调查了丹酚酸B的降胆固醇作用，并深入探讨了其潜在机制。通过高胆固醇饮食诱导建立高胆固醇血症小鼠模型。我们评估了血清和肝脏中的脂质参数，检查了肝脏的病理变化和基因表达改变。此外，我们利用16S rRNA检测了丹酚酸B对结肠内容物中肠道微生物群的影响。丹酚酸B显著降低了血清中的脂质水平，改善了肝脏中的脂质积累，并显著增加了粪便胆汁酸含量。RNA测序分析结果表明，丹酚酸B对初级胆汁酸生物合成有显著影响。此外，丹酚酸B增强了胆固醇7α-羟化酶（CYP7A1）和甾醇27-羟化酶（CYP27A1）的表达。此外，丹酚酸B抑制了产BSH细菌的丰度，并降低了法尼酯X受体（FXR）、成纤维细胞生长因子15（FGF-15）、顶端钠依赖性胆汁酸转运蛋白（ASBT）和回肠胆汁酸结合蛋白（I-BABP）的表达水平。综上所述，本研究表明，丹酚酸B通过抑制产BSH细菌的丰度和回肠FXR/FGF-15信号通路来增强胆汁酸的合成和排泄，从而改善高胆固醇血症。
