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Oxymatrine attenuates oxidized low‑density lipoprotein‑induced HUVEC injury by inhibiting NLRP3 inflammasome‑mediated pyroptosis via the activation of the SIRT1/Nrf2 signaling pathway

作者:Xin Jin, Wan Fu, Jiaxiu Zhou, Niannian Shuai, Yan Yang, Bo Wang · 发表于:International Journal of Molecular Medicine · 年份:2021 · DOI:10.3892/ijmm.2021.5020 · 被引用次数:87 · 研究领域:Inflammasome and immune disorders、Calcium signaling and nucleotide metabolism、COVID-19 Clinical Research Studies

Oxymatrine, a quinolizidine alkaloid isolated from the traditional Chinese herb Sophora flavescens Aiton, has been demonstrated to exert anti‑inflammatory and atherosclerotic effects, but the molecular mechanism has yet to be elucidated. Accumulating evidence indicates an important role of NLR family pyrin domain containing 3 (NLRP3) inflammasome‑mediated pyroptosis in the pathogenesis of atherosclerosis. The present study was undertaken to investigate whether oxymatrine attenuates oxidized low‑density lipoprotein (ox‑LDL)‑induced human umbilical vein endothelial cell (HUVEC) injury, an in vitro cell model of atherosclerosis, by inhibiting NLRP3 inflammasome‑mediated pyroptosis, and elucidate the role of the sirtuin (SIRT)1/nuclear factor‑erythroid 2‑related factor 2 (Nrf2) signaling pathway in this process. Cell viability and cytotoxicity were detected by CCK‑8 assay and a lactate dehydrogenase (LDH) assay kit. Cell apoptosis was detected by flow cytometry. Reactive oxygen species (ROS) generation was detected using a ROS assay kit. The malondialdehyde (MDA) content, mitochondrial membrane potential (MMP) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‑Px) activities were determined using commercial kits. The inflammatory cytokines levels were measured by ELISA and protein expression was monitored by western blot analysis. The results revealed that oxymatrine alleviated ox‑LDL‑induced cytotoxicity and apoptosis. Concurrently, oxymatrine ...