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

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.

Quanduzhong capsules for the treatment of grade 1 hypertension patients with low-to-moderate risk: A multicenter, randomized, double-blind, placebo-controlled clinical trial

“…Several animal models and patients with hypertension are reported to have gut dysbiosis, characterized by reduced diversity and an abnormal structure ( Sun et al, 2019 ). In a recent study by Yan D et al ( Yan et al, 2022 ), a high-salt diet and N (omega)-nitro-L-arginine methyl ester-induced hypertensive mice were treated with bark extract, which improved blood pressure, ameliorated kidney injury, decreased serum IL-6 and IL-17α as well as renal IL-17α, and restored gut microbiota diversity and composition. The potential gut bacteria involved in the antihypertensive action of DZ was suggested to be Parabacteroides strain XGB65, which exerted antihypertensive effects by lowering the levels of inflammatory cytokines such as renal IL-17α ( Yan et al, 2022 ).…”

Clinical study of Tongdu Shujin decoction in the treatment of ankylosing spondylitis with cold-dampness obstruction type: Study protocol for a randomized controlled trial

“…[ 20 ] Eucommia extract can reduce serum IL-6 and IL-17 levels and relieve inflammation. [ 21 ] The anti-inflammatory effect of rehmannia glutinosa is also particularly obvious, and its active ingredient catalpol can significantly decreased the expression of NF- κ B/NLRP3 inflammatory axis and inflammatory factors, inhibit tissue inflammation and relieve pain. [ 22 ] Meanwhile, its active ingredient aucubin also has anti-inflammatory and antioxidant pharmacological effects.…”

Quality Marker Discovery and Quality Evaluation of Eucommia ulmoides Pollen Using UPLC-QTOF-MS Combined with a DPPH-HPLC Antioxidant Activity Screening Method

“…The bark, leaves, stems, fruit, and flowers of EU possess an extensive range of pharmacological effects, such as anti-inflammatory [ 10 , 11 , 12 ], neuroprotective [ 13 , 14 ], and anti-hyperlipidemic [ 15 , 16 ]; treating secondary hypertension [ 17 , 18 , 19 ]; immunomodulatory effects [ 20 ]; and anti-hyperglycemic activities [ 21 ].…”