Wang Yuanyuan, Liu Siqi, Lu Keyi, Xu Erping, Wang Zhibin
Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan Province, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Front Pharmacol. 2025 May 19;16:1586705. doi: 10.3389/fphar.2025.1586705. eCollection 2025.
Abnormal elevations in the mortality of intestinal epithelial cells (IECs) are indicative of intestinal inflammation. Necroptosis of IECs represents a pro-inflammatory form of cell death, and modulation of IECs necroptosis may mitigate subsequent intestinal inflammation and preserve the integrity of the intestinal barrier. Currently, safe and effective preventive measures are lacking. In the Traditional Chinese Medicine theory, necroptosis of IECs leads to the destruction of the intestinal barrier in a manner associated with "heat and toxicity", exacerbating intestinal inflammation. Heat shock protein 90 (HSP90) has been identified as a regulator of key proteins involved in necroptosis signal pathway including RIPK1/3 and MLKL. Gambogic acid (GA), the primary active compound found in Hook. f., a traditional Chinese medicine used for detoxification and hemostasis, has not been studied for its potential therapeutic effects in ulcerative colitis previously. This study investigated the protective effects of GA on dextran sodium sulfate (DSS)-induced colitis in mice, as well as the underlying molecular mechanisms. GA was observed to significantly ameliorate DSS-induced enteritis and enhance intestinal barrier function. Concurrently, it reduced the phosphorylated expression levels of RIPK1/3 and MLKL. The underlying mechanism may be related to the suppression of HSP90 expression.
肠道上皮细胞（IECs）死亡率的异常升高表明肠道存在炎症。IECs的坏死性凋亡代表一种促炎性细胞死亡形式，调节IECs的坏死性凋亡可能减轻随后的肠道炎症并维持肠道屏障的完整性。目前，缺乏安全有效的预防措施。在中医理论中，IECs的坏死性凋亡以与“热毒”相关的方式导致肠道屏障破坏，加剧肠道炎症。热休克蛋白90（HSP90）已被确定为参与坏死性凋亡信号通路的关键蛋白（包括RIPK1/3和MLKL）的调节因子。藤黄酸（GA）是传统中药钩吻中发现的主要活性化合物，用于解毒和止血，此前尚未对其在溃疡性结肠炎中的潜在治疗作用进行研究。本研究调查了GA对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的保护作用及其潜在的分子机制。观察到GA可显著改善DSS诱导的肠炎并增强肠道屏障功能。同时，它降低了RIPK1/3和MLKL的磷酸化表达水平。潜在机制可能与抑制HSP90表达有关。
