Wang Yu, Chen Chaofan, Li Yushan, Li Ran, Wang Jinghan, Wu Chao, Chen Haonan, Shi Yingchao, Wang Shengfang, Gao Chuanyu
School of Physical Education, Henan University, Kaifeng, China, Kaifeng, China.
Henan Key Lab for Prevention and Control of Coronary Heart Disease, Zhengzhou, China.
PLoS One. 2025 Jun 6;20(6):e0325189. doi: 10.1371/journal.pone.0325189. eCollection 2025.
Kaempferol exhibits various biological activities, including antioxidant and anti-inflammatory effects. Its role in modulating lipid metabolism and inhibiting inflammatory responses to suppress the progression of atherosclerosis has been confirmed. However, its impact on macrophage pyroptosis and the underlying mechanisms remain unclear. This study aims to investigate the effects of kaempferol (Kae) on lipopolysaccharide (LPS)-induced macrophage pyroptosis and its potential mechanisms. In the experiments, we used the CCK8 assay to evaluate cell viability, ROS detection kits to measure intracellular reactive oxygen species (ROS) levels, Western Blot to detect the expression of proteins such as NOD-like receptor family pyrin domain-containing 3 (NLRP3), nuclear factor erythroid 2-related factor 2 (NRF2), gasdermin D (GSDMD), and heme oxygenase-1 (HO-1), and immunofluorescence to observe NRF2 nuclear translocation. The results showed that kaempferol alleviated LPS-induced cell viability decline and lactate dehydrogenase (LDH) release, inhibited excessive ROS generation, and suppressed NLRP3 inflammasome activation by increasing glutathione (GSH) and HO-1 levels, thereby reducing the expression of inflammatory factors. Additionally, kaempferol promoted NRF2 nuclear translocation, and the application of the NRF2 inhibitor ML385 reversed its antioxidant and anti-inflammatory effects. In vivo experiments further confirmed that kaempferol inhibited oxidative stress and reduced macrophage pyroptosis by activating the NRF2 pathway.
山奈酚具有多种生物学活性，包括抗氧化和抗炎作用。其在调节脂质代谢以及抑制炎症反应以抑制动脉粥样硬化进展方面的作用已得到证实。然而，其对巨噬细胞焦亡的影响及其潜在机制仍不清楚。本研究旨在探讨山奈酚（Kae）对脂多糖（LPS）诱导的巨噬细胞焦亡的影响及其潜在机制。在实验中，我们使用CCK8法评估细胞活力，使用ROS检测试剂盒测量细胞内活性氧（ROS）水平，使用蛋白质免疫印迹法检测含NOD样受体家族吡咯结构域蛋白3（NLRP3）、核因子红细胞2相关因子2（NRF2）、gasdermin D（GSDMD）和血红素加氧酶-1（HO-1）等蛋白质的表达，并使用免疫荧光法观察NRF2核转位。结果表明，山奈酚减轻了LPS诱导的细胞活力下降和乳酸脱氢酶（LDH）释放，抑制了过量ROS的产生，并通过提高谷胱甘肽（GSH）和HO-1水平抑制了NLRP3炎性小体的激活，从而降低了炎症因子的表达。此外，山奈酚促进了NRF2核转位，而应用NRF2抑制剂ML385可逆转其抗氧化和抗炎作用。体内实验进一步证实，山奈酚通过激活NRF2途径抑制氧化应激并减少巨噬细胞焦亡。
