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

Dong Yan; Wenhao Si; Xiaoyue Zhou; Mengjie Yang; Yuanhang Chen; Yahan Chang; Yidan Lu; Jieyu Liu; Kaiyue Wang; Moyu Yan; Feng Liu; Min Li; Xianliang Wang; Minna Wu; Zhongwei Tian; Haiyan Sun; Xiangfeng Song

doi:10.3389/fmicb.2022.967649

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

Front Microbiol. 2022 Aug 18:13:967649. doi: 10.3389/fmicb.2022.967649. eCollection 2022.

Authors

Dong Yan¹, Wenhao Si^{1

2}, Xiaoyue Zhou¹, Mengjie Yang¹, Yuanhang Chen¹, Yahan Chang¹, Yidan Lu¹, Jieyu Liu¹, Kaiyue Wang¹, Moyu Yan¹, Feng Liu¹, Min Li¹, Xianliang Wang³, Minna Wu¹, Zhongwei Tian², Haiyan Sun³, Xiangfeng Song⁴

Affiliations

¹ Xinxiang Key Laboratory of Pathogenic Biology, Department of Pathogenic Biology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
² Department of Dermatology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
³ Department of Cardiology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
⁴ Department of Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

Abstract

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.

Keywords: Eucommia ulmoides; IL-17A; Parabacteroides; gut microbiota; hypertension.