Zhang Jingwen, Li Hongyan, Wang Wei, Li Hong
Department of Endocrinology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, P.R. China.
Exp Ther Med. 2022 Apr;23(4):301. doi: 10.3892/etm.2022.11230. Epub 2022 Feb 22.
The present study aimed to investigate the anti-inflammatory effects of quercetin and the associated mechanisms involved. ELISA, reverse transcription-quantitative PCR and western blot analysis were performed to determine the anti-inflammatory effects of quercetin in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The molecular mechanisms of quercetin were investigated using network pharmacology, molecular docking technology and experiments. The results revealed that quercetin reduced the LPS-induced production of TNF-α, IL-6 and IL-1β in RAW264.7 macrophages. Protein-protein interaction network topology analysis indicated that Akt was the target of quercetin. Kyoto Encyclopedia of Genes and Genomes analysis indicated that quercetin may regulate the PI3K/Akt signaling pathway to exert its anti-inflammatory effects. Furthermore, the molecular docking results indicated that quercetin had a good affinity for the active sites of Akt. Western blot analysis confirmed that quercetin inhibited the phosphorylation of Akt, with an efficacy stronger than that of an Akt inhibitor. Taken together, Akt served as a target as part of the mechanism of the anti-inflammatory effect of quercetin. This result lays a foundation for the clinical application of quercetin in the treatment of inflammatory diseases.
本研究旨在探讨槲皮素的抗炎作用及其相关机制。采用酶联免疫吸附测定（ELISA）、逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质印迹分析来确定槲皮素对脂多糖（LPS）刺激的RAW264.7细胞的抗炎作用。利用网络药理学、分子对接技术和实验研究了槲皮素的分子机制。结果显示，槲皮素可降低LPS诱导的RAW264.7巨噬细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的产生。蛋白质-蛋白质相互作用网络拓扑分析表明，Akt是槲皮素的作用靶点。京都基因与基因组百科全书（KEGG）分析表明，槲皮素可能通过调节磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）信号通路发挥其抗炎作用。此外，分子对接结果表明，槲皮素与Akt的活性位点具有良好的亲和力。蛋白质印迹分析证实，槲皮素可抑制Akt的磷酸化，其效果强于Akt抑制剂。综上所述，Akt作为槲皮素抗炎作用机制的一部分发挥靶点作用。该结果为槲皮素在炎症性疾病治疗中的临床应用奠定了基础。
