Qi-Qi Xue, Chu-Hao Liu, Dong-Yan Zhang, Ming-Xuan Li, Yan Li
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Treatment with α-MG reduced BP, improved endothelial relaxation, and reversed aortic wall thickening and collagen deposition in Ang II-induced hypertensive mice. It also downregulated Ang II receptor 1 (AT1R) and angiotensin converting enzyme (ACE) expression, while upregulating ACE2, Mas receptor (MasR), and angiotensin (1-7) in the aorta. Moreover, α-MG demonstrated a significant enhancement in uric acid clearance and reduction in serum uric acid levels. Conversely, benzbromarone did not result in a decrease in BP, indicating that the hypotensive effect of α-MG may not be necessarily dependent on its urate-lowering properties. α-MG can attenuate Ang II-induced hypertension and reverse vascular remodeling, potentially by balancing the ACE/Ang II/AT1R axis and the ACE2/Ang-(1-7)/MasR axis. 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引用次数: 0
摘要
高尿酸血症是高血压的常见并发症,可能与高血压有因果关系。据报道,α-芒果苷(α-MG)具有降低尿酸的作用。本研究旨在探讨 α-MG 对血管紧张素 II(Ang II)注射高血压小鼠血压和尿酸水平的双重影响。雄性 C57BL/6 小鼠被随机分为五组:对照组、血管紧张素 II 输注组(500 ng/kg/min,持续 2 周)、血管紧张素 II 输注并分别灌胃给予 α-MG 4.0 和 8.0 mg/kg 及苯溴马隆(25 mg/kg)组。对血压、尿酸水平、血管结构和功能以及主动脉中肾素-Ang II 系统的表达进行了评估。在 Ang II 诱导的高血压小鼠体内,α-MG 可降低血压、改善内皮松弛、逆转主动脉壁增厚和胶原沉积。它还能下调 Ang II 受体 1(AT1R)和血管紧张素转换酶(ACE)的表达,同时上调主动脉中的 ACE2、Mas 受体(MasR)和血管紧张素(1-7)。此外,α-MG 还能显著提高尿酸清除率,降低血清尿酸水平。相反,苯溴马隆并没有导致血压下降,这表明α-MG 的降压作用不一定依赖于其降低尿酸的特性。α-MG 可以减轻 Ang II 诱导的高血压并逆转血管重塑,可能是通过平衡 ACE/Ang II/AT1R 轴和 ACE2/Ang-(1-7)/MasR 轴。我们的研究结果为α-MG作为一种新型抗高血压药物,尤其是用于高尿酸血症患者提供了启示。
α-Mangostin Attenuates Blood Pressure and Reverses Vascular Remodeling by Balancing ACE/AT1R and ACE2/Ang-(1-7)/MasR Axes in Ang II-Infused Hypertensive Mice.
Hyperuricemia is a common comorbidity of hypertension and probably has a causal relationship with hypertension. Alpha-mangostin (α-MG) has been reported to have uric acid lowering effect. This study aimed to investigate the dual effects of α-MG on blood pressure (BP) and uric acid levels in angiotensin II (Ang II)-infused hypertensive mice. Male C57BL/6 mice were randomized into five groups: control, Ang II infusion (500 ng/kg/min for 2 weeks), Ang II infusion with gavage administration of α-MG 4.0 and 8.0 mg/kg and benzbromarone (25 mg/kg) respectively. BP, uric acid levels, vascular structure and function, and renin-Ang II system expressions in the aorta were assessed. Treatment with α-MG reduced BP, improved endothelial relaxation, and reversed aortic wall thickening and collagen deposition in Ang II-induced hypertensive mice. It also downregulated Ang II receptor 1 (AT1R) and angiotensin converting enzyme (ACE) expression, while upregulating ACE2, Mas receptor (MasR), and angiotensin (1-7) in the aorta. Moreover, α-MG demonstrated a significant enhancement in uric acid clearance and reduction in serum uric acid levels. Conversely, benzbromarone did not result in a decrease in BP, indicating that the hypotensive effect of α-MG may not be necessarily dependent on its urate-lowering properties. α-MG can attenuate Ang II-induced hypertension and reverse vascular remodeling, potentially by balancing the ACE/Ang II/AT1R axis and the ACE2/Ang-(1-7)/MasR axis. Our findings provide insights into α-MG as a novel anti-hypertensive drug especially in patients with hyperuricemia.
期刊介绍:
Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field.
Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters.
By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.