International Journal of Clinical Case Reports 2024, Vol.14, No.5, 262-275 http://medscipublisher.com/index.php/ijccr 265 One of the significant findings from the study was the enrichment of the Parabacteroides strain, specifically ASV403, which was identified as a potential anti-hypertensive ASV. The closest strain, XGB65, was isolated and confirmed through animal studies to exert anti-hypertensive effects. This strain likely contributes to the reduction of inflammatory cytokines, such as renal IL-17A, thereby aiding in blood pressure reduction (Yan et al., 2022). 3.2 Nitric oxide (NO) pathway Eucommia ulmoides lignans (EuL) have been found to significantly increase plasma nitric oxide (NO) levels in spontaneously hypertensive rats (SHRs). In a study, SHRs treated with EuL at a dose of 300 mg/kg twice a day showed a marked increase in plasma NO levels. This increase in NO is crucial as it plays a significant role in vasodilation and blood pressure regulation (Luo et al., 2010). The vasorelaxant effects of Eucommia ulmoides are mediated through the NO pathway. Aqueous extracts from the leaf and bark of EU caused endothelium-dependent relaxation in vessels precontracted with phenylephrine. This relaxation was significantly inhibited by NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue, indicating the involvement of the NO synthase pathway. The study suggests that the NO-mediated relaxation is not mediated via the activation of endothelium muscarinic receptors but may involve the activation of K+ channels (Kwan et al., 2003). EU extract and its component geniposidic acid reduced blood pressure, and also that the endothelial nitric oxide synthase expression and NO bioavailability was improved and the decreased renal blood flow was reversed in Dahl salt-sensitive (DS) rats received 1% saline rats (Ishimitsu et al., 2021). 3.3 Renin-angiotensin system (RAS) Eucommia ulmoides lignans (EuL) also affect the renin-angiotensin system (RAS), which plays a critical role in blood pressure regulation. Long-term oral treatment with EuL at doses of 150 and 300 mg/kg twice a day resulted in decreased plasma renin activity (RA) and angiotensin II (Ang II) levels in SHRs. This reduction in RA and Ang II levels contributes to the antihypertensive effects of EuL by reducing the vasoconstrictive and sodium-retentive actions of Ang II (Luo et al., 2010). 3.4 Anti-inflammatory effects Eucommia ulmoides has demonstrated significant anti-inflammatory effects, which contribute to its antihypertensive properties. In the study involving high-salt diet and L-NAME induced hypertensive mice, EU treatment restored the levels of inflammatory cytokines, such as serum interleukin (IL)-6 and IL-17A, and renal IL-17A. The reduction in these inflammatory cytokines helps in mitigating inflammation-induced hypertension, thereby aiding in blood pressure reduction (Yan et al., 2022). 3.5 Antioxidant effects The antioxidant effects of Eucommia ulmoides are also noteworthy. Although specific studies on the upregulation of Nrf2 and downregulation of RAGE in the context of EU were not detailed in the provided data, it is well-established that antioxidants play a crucial role in combating oxidative stress, which is a significant factor in hypertension. The upregulation of Nrf2, a key regulator of antioxidant response, and the downregulation of RAGE, a receptor for advanced glycation end-products, would theoretically contribute to reducing oxidative stress and inflammation, thereby exerting antihypertensive effects. In summary, Eucommia ulmoides exerts its hypotensive effects through multiple mechanisms, including the regulation of gut microbiota, enhancement of NO-mediated vasorelaxation, modulation of the renin-angiotensin system, and anti-inflammatory and antioxidant effects. These multifaceted actions make EU a promising candidate for the development of novel antihypertensive treatments (Kwan et al., 2003; Luo et al., 2010; Yan et al., 2022). 4 In Vitro Studies 4.1 Effects on isolated blood vessels In vitro studies have demonstrated that extracts fromEucommia ulmoides Oliv. exhibit significant vasorelaxant effects on isolated blood vessels. The aqueous extracts from both the leaf and bark of Eucommia ulmoides have
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