Puerarin alleviates acrolein-induced atherosclerosis by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit the activation of inflammasome

IF 3.2 4区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biotechnology and applied biochemistry Pub Date : 2024-05-23 DOI:10.1002/bab.2603

XiaoNing Li, YeTing Li, HuiHui Jiao, AiTing Wang, Man Zheng, ChunYan Xiang, FengLei Zhang

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引用次数: 0

Abstract

Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression.

In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK-8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr-fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome-related proteins, and the inhibition of MYH9 significantly impaired Pue-induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3-mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr-induced AS by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation.

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葛根素通过激活 MYH9 介导的 SIRT1/Nrf2 级联抑制炎症小体的活化，从而缓解丙烯醛诱导的动脉粥样硬化。

葛根素（Pue）具有显著的抗氧化和抗炎特性。本研究旨在阐明和探讨葛根素在动脉粥样硬化（AS）进展中的潜在机制。在体内，通过饮用水吸入丙烯醛（Acr）来构建 AS 模型。在体外，使用 CCK-8 检测法和乳酸脱氢酶（LDH）检测试剂盒检测细胞活力。流式细胞术检测细胞凋亡。丙二醛（MDA）含量用商品试剂盒测定，炎症因子水平用酶联免疫吸附法测定，蛋白质用 Western 印迹法测定。Pue能有效降低Acr喂养小鼠的血脂水平。Pue能抑制氧化应激、动脉粥样硬化斑块的形成和主动脉组织学变化过程。Pue 预处理可降低 HUVECs 中的 MDA，维持抗氧化酶的活性。Pue 上调了 HUVECs 中的 SIRT1/Nrf2 级联。Pue 增加了 MYH9 并抑制了 NLRP3 炎症体相关蛋白，抑制 MYH9 能显著降低 Pue 诱导的 Nrf2 激活。此外，除了 Acr 诱导的 HUVEC NLRP3 介导的热凋亡外，Pue 还减轻了 HUVEC 的细胞毒性和细胞凋亡。MYH9 抑制剂能有效抑制 Acr 诱导的热凋亡，防止 HUVEC 损伤。此外，Pue 还能促进 HUVECs 中 SIRT1/Nrf2 级联的活化。Pue可能通过激活MYH9介导的SIRT1/Nrf2级联来抑制炎性体的激活，从而缓解Acr诱导的强直性脊柱炎。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology and applied biochemistry 工程技术-生化与分子生物学

CiteScore

6.00

自引率

7.10%

发文量

117

审稿时长

3 months

期刊介绍： Published since 1979, Biotechnology and Applied Biochemistry is dedicated to the rapid publication of high quality, significant research at the interface between life sciences and their technological exploitation. The Editors will consider papers for publication based on their novelty and impact as well as their contribution to the advancement of medical biotechnology and industrial biotechnology, covering cutting-edge research in synthetic biology, systems biology, metabolic engineering, bioengineering, biomaterials, biosensing, and nano-biotechnology.