State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, China.
Internal Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
Nutrients. 2022 May 9;14(9):1983. doi: 10.3390/nu14091983.
Hyperuricemia is one of the independent risk factors for atherosclerotic cardiovascular disease. Herein, we investigate the association between uric acid and cholesterol metabolism and the effect of dioscin on the prevention of hyperuricemia-induced atherosclerosis. In the potassium oxonate-treated ApoE mice, atherosclerosis was accelerated along with elevated serum cholesterol levels in the hyperuricemic state, which can be ameliorated by dioscin. Together with the in vitro assays, we found that the effect of dioscin was at least partially through the regulation of the farnesoid X receptor (FXR) -small heterodimer partner (SHP) -7α-hydroxylase (CYP7A1) signaling pathway in the liver. Tigogenin (a metabolite of dioscin) suppressed FXR activation and increased CYP7A1, resulting in an increased conversion rate of cholesterols into bile acids. Further clinical study revealed that treatment with a dioscin-enriched preparation decreased serum cholesterol levels in individuals with hyperuricemia. In summary, this study demonstrated a slowdown effect of dioscin on the progression of hyperuricemia-induced atherosclerosis.
高尿酸血症是动脉粥样硬化性心血管疾病的独立危险因素之一。本研究旨在探讨尿酸与胆固醇代谢之间的关系，并研究薯蓣皂苷对防治高尿酸血症诱导的动脉粥样硬化的作用。在氧嗪酸钾处理的载脂蛋白 E 基因敲除（ApoE-/-）小鼠模型中，高尿酸血症状态下血清胆固醇水平升高，加速了动脉粥样硬化的发生，薯蓣皂苷可减轻这种情况。结合体外实验，我们发现薯蓣皂苷的作用至少部分是通过调节肝脏中的法尼醇 X 受体（FXR）-小异二聚体伴侣（SHP）-7α-羟化酶（CYP7A1）信号通路实现的。薯蓣皂苷元（薯蓣皂苷的代谢产物）抑制 FXR 的激活并增加 CYP7A1，从而增加胆固醇转化为胆汁酸的转化率。进一步的临床研究表明，薯蓣皂苷富集制剂的治疗可降低高尿酸血症患者的血清胆固醇水平。综上所述，本研究表明薯蓣皂苷可减缓高尿酸血症诱导的动脉粥样硬化的进展。
