Abstract：
The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100β)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100β+ EGCs while promoting the differentiation of GFAP+/S100β+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100β+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.
摘要：
双氢青蒿素（DHA）缓解结肠炎的治疗作用的确切机制仍未完全了解。炎症结肠组织中胶质纤维酸性蛋白(GFAP)+/S100钙结合蛋白B(S100β)+肠胶质细胞(EGC)的升高与慢性结肠炎中观察到的肠上皮屏障(IEB)和肠血管屏障(GVB)的破坏之间存在很强的相关性。DHA在恢复双肠屏障的功能同时减轻肠道炎症方面表现出功效。机械上,DHA抑制GFAP+EGCs向GFAP+/S100β+EGCs的转化,同时促进GFAP+/S100β+EGCs向GFAP+EGCs的分化。此外，DHA通过在G0/G1期诱导细胞周期停滞在GFAP/S100βEGC中诱导细胞凋亡。初始机制进一步验证了DHA通过改善结肠炎中的生态失调来调节EGC异质性。这些发现强调了DHA通过改善菌群失调改善结肠炎的多方面治疗潜力。调节EGC异质性，并保持肠道屏障的完整性，从而为炎症性肠病的新治疗策略提供了有希望的途径。
