肠上皮细胞过度凋亡导致肠道屏障功能障碍，这不仅是炎症性肠病（IBD）的病理特征之一，也是治疗靶点。据报道，天然植物提取物银杏素 (GK) 具有抗细胞凋亡活性，但其在 IBD 中的作用尚不清楚。本研究旨在探讨GK是否具有抗结肠炎作用及相关机制。建立了由右旋糖酐硫酸钠 (DSS) 诱导的实验性结肠炎模型，发现 GK 可以缓解 DSS 诱导的小鼠结肠炎，表现为体重减轻、结肠缩短、疾病活动指数 (DAI)、宏观和组织评分的改善，和促炎介质。此外，在 DSS 小鼠和 TNF-α 诱导的结肠类器官中，GK 通过改善通透性、抑制凋亡细胞数量和关键凋亡调节因子（cleaved caspase 3、Bax）的表达，保护肠屏障并抑制肠上皮细胞凋亡。和Bcl-2)。通过生物信息学、拯救实验和分子对接等手段探讨GK保护作用的潜在机制，发现GK可能直接靶向并激活EGFR，从而干扰PI3K/AKT信号传导，抑制体内外肠上皮细胞的凋亡。总之，GK至少部分通过激活EGFR和干扰PI3K/AKT激活来抑制实验性结肠炎小鼠的肠上皮细胞凋亡，解释了改善结肠炎的潜在机制，这可能为IBD的治疗提供新的选择。© 2024 作者。 FASEB 期刊由 Wiley periodicals LLC 代表美国实验生物学学会联合会出版。

Excessive apoptosis of intestinal epithelial cells leads to intestinal barrier dysfunction, which is not only one of the pathological features of inflammatory bowel disease (IBD) but also a therapeutic target. A natural plant extract, Ginkgetin (GK), has been reported to have anti-apoptotic activity, but its role in IBD is unknown. This study aimed to explore whether GK has anti-colitis effects and related mechanisms. An experimental colitis model induced by dextran sulfate sodium (DSS) was established, and GK was found to relieve colitis in DSS-induced mice as evidenced by improvements in weight loss, colon shortening, Disease Activity Index (DAI), macroscopic and tissue scores, and proinflammatory mediators. In addition, in DSS mice and TNF-α-induced colonic organoids, GK protected the intestinal barrier and inhibited intestinal epithelial cell apoptosis, by improving permeability and inhibiting the number of apoptotic cells and the expression of key apoptotic regulators (cleaved caspase 3, Bax and Bcl-2). The underlying mechanism of GK's protective effect was explored by bioinformatics, rescue experiments and molecular docking, and it was found that GK might directly target and activate EGFR, thereby interfering with PI3K/AKT signaling to inhibit apoptosis of intestinal epithelial cells in vivo and in vitro. In conclusion, GK inhibited intestinal epithelial apoptosis in mice with experimental colitis, at least in part, by activating EGFR and interfering with PI3K/AKT activation, explaining the underlying mechanism for ameliorating colitis, which may provide new options for the treatment of IBD.© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.