Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong Pharmaceutical University, Guangzhou, China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Food Funct. 2022 Jul 4;13(13):6987-6999. doi: 10.1039/d2fo00038e.
Chlorogenic acid (CGA) is a natural compound with many important pharmacological effects including anti-hypertension. This study aimed to investigate the anti-hypertensive effect of CGA on high-fructose-induced salt-sensitive hypertension and the underlying mechanism. Hypertension was induced in male C57BL/6 mice by 20% fructose in drinking water plus 4% sodium chloride in the diet (HFS) for 8 weeks. CGA (50, 100 or 200 mg kg d) was orally administered to HFS-treated mice. The blood pressure of mice was recorded the tail cuff method. The structure of gut microbiota and profiles of bile acids (BAs) in the serum were determined. Here, we found that HFS-elevated systolic blood pressure was greatly attenuated by CGA. The microbiota analysis showed that CGA restructured the HFS-treated gut microbiota, and markedly enriched . Oral administration of a isolate, , also exhibited an anti-hypertensive effect in HFS-fed mice. Furthermore, we found that CGA and CGA-enriched enhanced the expression of colonic Farnesoid X Receptor (FXR), modulated BA metabolism and enriched some BAs including deoxycholic acid (DCA) in the serum of HFS-fed mice. Treatment with DCA improved phenylephrine-induced vasoconstriction in arterioles of mice and attenuated hypertension in HFS-fed mice, suggesting that DCA serves as a link between gut microbiota and blood pressure. Our results clearly demonstrate that CGA attenuates HFS-induced hypertension in mice by modulating gut microbiota and BA metabolism. These findings provide insights into the potential mechanism of CGA for the treatment of hypertension.
绿原酸（CGA）是一种天然化合物，具有许多重要的药理作用，包括抗高血压。本研究旨在探讨 CGA 对高果糖诱导的盐敏感高血压的降压作用及其机制。雄性 C57BL/6 小鼠通过饮用 20%果糖加 4%氯化钠饮食（HFS）8 周诱导高血压。CGA（50、100 或 200mgkgd）灌胃 HFS 处理的小鼠。通过尾套法记录小鼠血压。测定血清中肠道微生物群结构和胆汁酸（BAs）谱。结果发现，CGA 显著降低 HFS 引起的收缩压升高。微生物群分析表明，CGA 重构了 HFS 处理的肠道微生物群，并显著富集了。口服分离的，也表现出抗高血压作用在 HFS 喂养的小鼠。此外，我们发现 CGA 和 CGA 富集的增加了结肠法尼醇 X 受体（FXR）的表达，调节了 BA 代谢，并在 HFS 喂养的小鼠的血清中富集了一些 BA，包括脱氧胆酸（DCA）。DCA 处理改善了苯肾上腺素诱导的小鼠小动脉收缩，并减轻了 HFS 喂养小鼠的高血压，表明 DCA 是肠道微生物群和血压之间的联系。我们的研究结果清楚地表明，CGA 通过调节肠道微生物群和 BA 代谢来减轻 HFS 诱导的小鼠高血压。这些发现为 CGA 治疗高血压的潜在机制提供了新的见解。
