Naringenin Alleviates the Autophagy-Associated AMPK-Akt/mTOR Pathway to Regulate Inflammation and Barrier Function, Decreasing DSS-Induced Intestinal Fibrosis

作者：Keying Wang, Chun-Xiang Huang, Xiaojia Hu, Junyang Liu, Xiao‐Hui Qin, Chen-Xi Tong, Zhiqiang Liu, Wen He, Tiemin Jiang, Jia‐Le Song · 发表于：ACS Omega · 年份：2025 · DOI：10.1021/acsomega.5c03232 · 被引用次数：7 · 研究领域：Autophagy in Disease and Therapy、Phagocytosis and Immune Regulation

The development of strictures due to intestinal fibrosis remains a significant clinical challenge in patients with ulcerative colitis (UC). The purpose of this experiment was to investigate the protective effects of naringenin (NAR, 40 mg/kg), a natural flavonoid predominantly present in grapes and oranges, against dextran sodium sulfate (DSS, 2.5%)-induced intestinal fibrosis in UC mice. Oral administration of NAR effectively mitigated clinical symptoms and histological damage in UC mice by reducing the colonic F4/80 and MPO levels. Additionally, NAR lowered the serum concentrations of proinflammatory cytokines and inhibited NLRP3 inflammasome activation in the colon. NAR regulates the Nrf2/Keap1 pathway to combat oxidative damage caused by DSS and enhance autophagy through the AMPK-Akt/mTOR pathway, ultimately decreasing intestinal fibrosis in UC mice by inhibiting α-SMA and Collagen-I. Taken together, our findings demonstrate that NAR can prevent the occurrence and progression of intestinal fibrosis. This effect is achieved by adjusting the AMPK-Akt/mTOR pathway and the promotion of autophagy at the molecular level.