香草酸通过增强NO信号通路减轻单芥碱诱导的肺动脉高压

IF 1.4 4区医学 Q4 CHEMISTRY, MEDICINAL

Natural Product Communications Pub Date : 2022-09-01 DOI:10.1177/1934578X221128411

Shan X Wang, Xuyang Sun, Zhuguo Wang, S. Zhou, Shanshan Su, Xingmei Nan, D. Lu, Zhanqiang Li

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引用次数: 2

摘要

肺动脉高压(PAH)是一种严重的进行性疾病，其特征是平均肺动脉压升高，右心室肥厚，最终进展为右心衰和死亡。本研究旨在探讨天然产物香草酸(VA)对MCT诱导的大鼠多环芳烃的影响。并对VA的精氨酸酶抑制活性和酶动力学反应进行了研究。结果表明，VA可改善MCT所致大鼠肺动脉压、肺动脉血管重构和右心室重构，降低肺组织纤维化程度。此外，VA下调Hif-2α、Hif-1β和Arg2的基因和蛋白表达水平，增加P-eNOS/eNOS水平，从而增加PAH大鼠一氧化氮(NO)水平。此外，VA是一种混合竞争性精氨酸酶抑制剂，IC50为26.1 μM。综上所述，精氨酸酶抑制剂VA通过增强NO信号通路对mct诱导的PAH和肺血管重构具有保护作用。

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Vanillic Acid Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension by Enhancing NO Signaling Pathways

Pulmonary arterial hypertension (PAH) is a severe progressive disease characterized by elevated mean pulmonary arterial pressure, right ventricular hypertrophy, and eventual progression to right heart failure and death. This study aimed to examine the effect of the natural product vanillic acid (VA) on monocrotaline (MCT)-induced PAH in rats. The arginase inhibitory activity and enzyme kinetic reaction of VA were also investigated. The results showed that VA could improve pulmonary arterial pressure, pulmonary artery vascular remodeling, and right ventricular remodeling induced by MCT in rats and reduce the degree of pulmonary tissue fibrosis. Moreover, VA downregulated the gene and protein expression levels of Hif-2α, Hif-1β, and Arg2 and increased the P-eNOS/eNOS levels, thus increasing nitric oxide (NO) levels in PAH rats. Furthermore, VA was determined to be a mixed competitive arginase inhibitor with an IC50 of 26.1 μM. In conclusion, the arginase inhibitor VA exerted protective effects on MCT-induced PAH and pulmonary vascular remodeling by enhancing NO signaling pathways.

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来源期刊

Natural Product Communications 工程技术-食品科技

CiteScore

3.10

自引率

11.10%

发文量

254

审稿时长

2.7 months

期刊介绍： Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products. Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products. Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products.