Zeng H B, Zhang L H, Yuan D P, Wang W, Su X M, Weng W X, Miao R, Xu J Y, Long J, Song Y H
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Mol Biol (Mosk). 2023 Jan-Feb;57(1):106-108. doi: 10.31857/S0026898423010196.
As a byproduct of mitochondrial respiration or metabolism, reactive oxygen species (ROS) can act as a signaling molecule to activate NLR family pyrin domain containing 3 (NLRP3) inflammasome, thereby triggering immune response. NLRP3 inflammasome acts as a sensor of various danger signals and is central to the control of pyroptosis occurrence. Macrophage pyroptosis is closely related to atherosclerosis, arthritis, pulmonary fibrosis and other inflammatory diseases. Methylophiopogonanone A (MO-A) is a main homoisoflavonoid in Chinese herb Ophiopogonis Radix, which has antioxidant effect. However, it is not clear whether MO-A can alleviate macrophage pyroptosis by inhibiting oxidative stress. Here we have shown that MO-A increases the activities of superoxide dismutase (SOD) and catalase (CAT), inhibits the production of ROS, reduces the activation of NLRP3 inflammasome and the release of lactate dehydrogenase (LDH), and inhibits pyroptosis in macrophages induced by lipopolysaccharides (LPS) and adenosine triphosphate (ATP). These effects can be reversed by the ROS promoter H2O2. Therefore, MO-A can inhibit macrophage pyroptosis through the ROS/NLRP3 pathway and may be considered as a candidate drug for the treatment of inflammatory diseases.
作为线粒体呼吸或代谢的副产物，活性氧（ROS）可作为信号分子激活含NLR家族吡啶结构域3（NLRP3）炎性小体，从而触发免疫反应。NLRP3炎性小体作为各种危险信号的传感器，在控制细胞焦亡发生中起核心作用。巨噬细胞焦亡与动脉粥样硬化、关节炎、肺纤维化等炎症性疾病密切相关。麦冬甲基黄烷酮A（MO-A）是中药麦冬中的主要同型异黄酮，具有抗氧化作用。然而，尚不清楚MO-A是否能通过抑制氧化应激来减轻巨噬细胞焦亡。在此我们发现，MO-A可增加超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性，抑制ROS的产生，减少NLRP3炎性小体的激活和乳酸脱氢酶（LDH）的释放，并抑制脂多糖（LPS）和三磷酸腺苷（ATP）诱导的巨噬细胞焦亡。这些作用可被ROS促进剂H2O2逆转。因此，MO-A可通过ROS/NLRP3途径抑制巨噬细胞焦亡，可能被视为治疗炎症性疾病的候选药物。
