Gentiana szechenyii Kanitz Compounds Regulate Lipopolysaccharide‐Induced Inflammation and Mitochondrial Autophagy Via the Toll‐Like Receptor 4‐Nuclear Factor Kappa B Pathway

Inflammation plays a key role in the progression and prognosis of most diseases. Mitochondrial autophagy has been demonstrated to correlate with inflammatory processes. The anti-inflammatory Tibetan medicinal herb Gentiana szechenyii Kanitz (GS) exhibits mechanisms of action in inflammation and mitochondrial autophagy that remain incompletely elucidated. This study aims to elucidate the effects of GS on inflammatory cytokines, oxidative stress, and the TLR4/NF-κB signaling pathway, whilst revealing its potential targeted action in ameliorating inflammatory responses through regulation of the mitochondrial autophagy pathway. The effects of GS on the TLR4/NF-κB pathway were evaluated via enzyme-linked immunosorbent assay (ELISA), flow cytometry, western blotting (WB), and proteomics, whilst investigating the role of mitochondrial autophagy in inflammatory mechanisms. GS significantly reduced cell apoptosis, decreased the release of proinflammatory cytokines and ROS, inhibited the TLR4/NF-κB signaling pathway, and suppressed mitochondrial autophagy, indicating that GS compounds can prevent LPS-induced pathological mitochondrial autophagy. GS exhibits significant anti-inflammatory and antioxidant effects in vitro, with its mechanism of action involving regulation of the TLR4/NF-κB pathway and mitochondrial autophagy markers, thereby alleviating inflammation in RAW264.7 cells. This study provides valuable insights into the potential therapeutic mechanisms of GS in inflammatory diseases.