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富含醉鱼草苷的醉鱼草提取物通过抑制肠道来源的LPS/TLR4途径对代谢性高血压大鼠产生有益作用。

Buddleoside-Rich L. Extract has a Beneficial Effect on Metabolic Hypertensive Rats by Inhibiting the Enteric-Origin LPS/TLR4 Pathway.

作者信息

Wang Ya-Jun, Su Jie, Yu Jing-Jing, Yan Mei-Qiu, Shi Meng-Lin, Huang Qi-Di, Li Bo, Wu Wen-Yan, Xia Rong-Shuang, Li Si-Fan, Chen Su-Hong, Lv Gui-Yuan

机构信息

School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, China.

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, China.

出版信息

Front Pharmacol. 2021 Oct 8;12:755140. doi: 10.3389/fphar.2021.755140. eCollection 2021.

DOI:10.3389/fphar.2021.755140
PMID:34690786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8532163/
Abstract

As the number of patients with metabolic hypertension (MH) is increasing, there is an essential require for global measures to prevent and treat MH. Flavonoids such as buddleoside (BUD) from L. are the main pharmacological components of cardiovascular activities. Previous studies have suggested that the buddleoside-rich L. extract (BUDE) can reduce blood pressure in spontaneously hypertensive rats (SHR). However, its effect on MH and how it works remains to be researched. In this study, it was observed that BUDE could lower blood pressure, improve dyslipidemia, and decrease the level of plasma LPS in MH rats. Moreover, BUDE improved intestinal flora and increased the expression of occludin and claudin-1 in the colon, and improved the pathological injury of the colon. Western bolt and qRT-PCR experiments showed that BUDE could down-regulate TLR4 and MyD88 protein and mRNA expression and inhibit phosphorylation of IKKβ, IκBα and NF-κB p65 in vessels of MH rats. These results showed that BUDE could regulate intestinal flora, improve intestinal barrier function, reduce the production and penetration of LPS, thereby inhibiting the vascular TLR4/MyD88 pathway, improving vascular endothelial function, and ultimately lowering blood pressure in MH rats. This study provides a new mechanism of BUDE against MH by inhibiting the enteric-origin LPS/TLR4 pathway.

摘要

随着代谢性高血压(MH)患者数量的增加,全球范围内对预防和治疗MH的措施有着迫切需求。来自醉鱼草属植物的黄酮类化合物如醉鱼草苷(BUD)是心血管活性的主要药理成分。先前的研究表明,富含醉鱼草苷的醉鱼草属植物提取物(BUDE)可降低自发性高血压大鼠(SHR)的血压。然而,其对MH的作用及其作用机制仍有待研究。在本研究中,观察到BUDE可降低MH大鼠的血压,改善血脂异常,并降低血浆LPS水平。此外,BUDE改善了肠道菌群,增加了结肠中闭合蛋白和 Claudin-1的表达,并改善了结肠的病理损伤。蛋白质免疫印迹和qRT-PCR实验表明,BUDE可下调MH大鼠血管中TLR4和MyD88蛋白及mRNA表达,并抑制IKKβ、IκBα和NF-κB p65的磷酸化。这些结果表明,BUDE可调节肠道菌群,改善肠道屏障功能,减少LPS的产生和渗透,从而抑制血管TLR4/MyD88途径,改善血管内皮功能,最终降低MH大鼠的血压。本研究通过抑制肠道源性LPS/TLR4途径,为BUDE抗MH提供了一种新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e5/8532163/e66180ff71ff/fphar-12-755140-g009.jpg
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