Table_1_Eucommia ulmoides bark extract reduces blood pressure and inflammation by regulating the gut microbiota and enriching the Parabacteroides strain in high-salt diet and N(omega)-nitro-L-arginine methyl ester induced mice.XLSX

Hypertension is a major threat to human health. Eucommia ulmoides Oliv. (EU) is a small tree and EU extract is widely used to improve hypertension in East Asia. However, its major constituents have poor absorption and stay in the gut for a long time. The role of the gut microbiota in the anti-hypertensive effects of EU is unclear. Here, we examined the anti-hypertensive effects of EU in high-salt diet and N(omega)-nitro-L-arginine methyl ester (L-NAME) induced mice. After receiving EU for 6 weeks, the blood pressure was significantly reduced and the kidney injury was improved. Additionally, EU restored the levels of inflammatory cytokines, such as serum interleukin (IL)-6 and IL-17A, and renal IL-17A. The diversity and composition of the gut microbiota were influenced by administration of EU; 40 significantly upregulated and 107 significantly downregulated amplicon sequence variants (ASVs) were identified after administration of EU. ASV403 (Parabacteroides) was selected as a potential anti-hypertensive ASV. Its closest strain XGB65 was isolated. Furthermore, animal studies confirmed that Parabacteroides strain XGB65 exerted anti-hypertensive effects, possibly by reducing levels of inflammatory cytokines, such as renal IL-17A. Our study is the first to report that EU reduces blood pressure by regulating the gut microbiota, and it enriches the Parabacteroides strain, which exerts anti-hypertensive effects. These findings provide directions for developing novel anti-hypertensive treatments by combining probiotics and prebiotics.

高血压（hypertension）是危及人类健康的重大健康威胁。杜仲（Eucommia ulmoides Oliv.，简称EU）是一种小型乔木，其提取物在东亚地区被广泛用于改善高血压症状。然而，其主要活性成分吸收率较低，且会在肠道内长时间滞留。目前，肠道菌群在杜仲提取物降压作用中的调控机制尚不明确。本研究以高盐饮食联合Nω-硝基-L-精氨酸甲酯（N(omega)-nitro-L-arginine methyl ester，L-NAME）诱导的高血压小鼠为模型，探究了杜仲提取物的降压作用。连续给药6周后，模型小鼠的血压显著降低，肾脏损伤状况得到改善。此外，杜仲提取物可恢复血清白细胞介素（interleukin，IL）-6、IL-17A以及肾脏组织中IL-17A的炎症因子水平至正常范围。给药杜仲提取物可显著改变小鼠肠道菌群的多样性与群落组成：经处理后，共鉴定出40个显著上调、107个显著下调的扩增子序列变体（amplicon sequence variants，ASVs）。其中ASV403（副拟杆菌属，Parabacteroides）被筛选为潜在的降压相关扩增子序列变体。研究人员成功分离得到其亲缘关系最近的菌株XGB65。进一步的动物实验证实，副拟杆菌属菌株XGB65可发挥降压作用，其潜在机制可能为降低肾脏组织中IL-17A等炎症因子的水平。本研究首次报道杜仲提取物可通过调控肠道菌群发挥降压作用，且其降压功效与富集副拟杆菌属菌株密切相关。本研究结果为开发益生菌与益生元联合使用的新型降压治疗方案提供了重要研究方向。