Ye Bozhi, Cai Xueli, Liang Xiaohe, Chen Yunxuan, Dai Shanshan, Huang Zhuqi, Huang Weijian, Zhang Lei, Wang Zixuan, Xing Jincheng, Lai Xianhui, Huang Zhouqing, Jia Zhuyin
Department of Cardiology, Panvascular Disease Management Center (PDMC), Wenzhou Central Hospital, The Dingli Clinical College of Wenzhou Medical University, WenZhou, ZheJiang, China.
The Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of WenZhou Medical University, WenZhou, ZheJiang, China.
Cardiovasc Drugs Ther. 2024 Dec 24. doi: 10.1007/s10557-024-07659-w.
Inflammatory responses induced by NLRP3 inflammasome contribute to the progression of atherosclerosis. This study seeks to investigate the effect of emodin on the NLRP3 inflammasome in atherogenesis and to probe the underlying mechanism.
ApoE-knockout (ApoE) mice were treated with a high-fat diet (HFD) for 12 weeks and intragastrically with emodin for 6 weeks. Human mononuclear cell line THP-1 was pretreated with emodin or signaling pathway inhibitors and induced into macrophages using phorbol 12-myristate 13-acetate (PMA) for 48 h. The NLRP3-mediated inflammatory response was studied both in vivo and in vitro. The level of the inflammation was detected by western blot, real-time PCR analysis, and ELISA.
Emodin attenuated atherosclerotic lesions in HFD-treated ApoE mice. Emodin dramatically decreased the expression of NLRP3, GSDMD, IL-1β, and IL-18 in HFD-treated ApoE mice and PMA-induced macrophages. Moreover, emodin significantly hindered the activation of nuclear factor kappa-B (NF-κB) by inhibiting the formation of the TLR4/MyD88 complex in PMA-induced macrophages.
Our data demonstrate that emodin can inhibit the development of atherosclerotic plaques by alleviating NLRP3/GSDMD-induced inflammation through repressing the TLR4/MyD88/NF-κB signaling pathway in macrophages. This finding suggests that emodin can be a potential candidate for the treatment of atherosclerosis.
NLRP3炎性小体诱导的炎症反应有助于动脉粥样硬化的进展。本研究旨在探讨大黄素对动脉粥样硬化形成过程中NLRP3炎性小体的影响，并探究其潜在机制。
给载脂蛋白E基因敲除（ApoE）小鼠喂食高脂饮食（HFD）12周，并灌胃给予大黄素6周。人单核细胞系THP-1用大黄素或信号通路抑制剂预处理，并用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导成巨噬细胞48小时。在体内和体外研究NLRP3介导的炎症反应。通过蛋白质免疫印迹法、实时荧光定量PCR分析和酶联免疫吸附测定法检测炎症水平。
大黄素减轻了高脂饮食处理的ApoE小鼠的动脉粥样硬化病变。大黄素显著降低了高脂饮食处理的ApoE小鼠和PMA诱导的巨噬细胞中NLRP3、GSDMD、IL-1β和IL-18的表达。此外，大黄素通过抑制PMA诱导的巨噬细胞中TLR4/MyD88复合物的形成，显著阻碍了核因子κB（NF-κB）的激活。
我们的数据表明，大黄素可通过抑制巨噬细胞中TLR4/MyD88/NF-κB信号通路，减轻NLRP3/GSDMD诱导的炎症，从而抑制动脉粥样硬化斑块的形成。这一发现表明，大黄素可能是治疗动脉粥样硬化的潜在候选药物。
