Qin Qin, Dong Qingjun, Pan Yan, Wang Chen, Lu Jingen
Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People's Republic of China.
Department of Anal & Intestinal Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People's Republic of China.
Sci Rep. 2025 Jul 2;15(1):22509. doi: 10.1038/s41598-025-06021-w.
Ulcerative colitis (UC) is a chronic, idiopathic inflammatory disease affecting the gastrointestinal tract. Hongyuyin (HYY), a traditional Chinese botanical formulation, has been effectively treating UC for over three decades; however, its underlying biological mechanism of action in UC-associated intestinal fibrosis (IF) remains unclear. This study investigated the mechanisms of action of HYY on IF through in vivo experiments using a dextran sulfate sodium (DSS)-induced mouse colitis model. Clinical symptoms, colonic pathological damage, inflammation, and fibrosis were monitored across all groups. Both transcriptomic analysis and network pharmacology (NP) techniques were utilized to elucidate the mechanistic insights. HYY treatment substantially reduced inflammation, fibroblast activation, and collagen deposition in UC mice. KEGG analyses suggested that HYY treatment modulated multiple signaling pathways, notably the TNF, IL-17, and PI3K-Akt signaling pathways. Combined analysis identified the PI3K-Akt signaling pathway as a major contributor, with high enrichment factors and numerous enrichment genes involved (IL-6, CSF3, SPP1, AKT1, PIK3CA, and so on) in UC-associated IF. Western blotting confirmed significant reductions in both p-AKT/AKT and p-mTOR/mTOR ratios after HYY treatment. Collectively, HYY alleviates UC-associated IF by reducing the phosphorylation of PI3K-Akt pathway factors, thereby inhibiting fibroblast activation and collagen deposition. This research provides novel insights into HYY's mechanism of action in UC-associated IF management.
溃疡性结肠炎（UC）是一种影响胃肠道的慢性特发性炎症性疾病。红玉饮（HYY）是一种传统的中药配方，三十多年来一直有效治疗UC；然而，其在UC相关肠道纤维化（IF）中的潜在生物学作用机制仍不清楚。本研究通过使用葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎模型进行体内实验，研究了HYY对IF的作用机制。监测所有组的临床症状、结肠病理损伤、炎症和纤维化情况。利用转录组分析和网络药理学（NP）技术来阐明作用机制。HYY治疗显著减轻了UC小鼠的炎症、成纤维细胞活化和胶原沉积。KEGG分析表明，HYY治疗调节了多个信号通路，尤其是TNF、IL-17和PI3K-Akt信号通路。联合分析确定PI3K-Akt信号通路是主要贡献者，在UC相关IF中具有高富集因子和众多参与的富集基因（IL-6、CSF3、SPP1、AKT1、PIK3CA等）。蛋白质印迹法证实HYY治疗后p-AKT/AKT和p-mTOR/mTOR比值均显著降低。总体而言，HYY通过降低PI3K-Akt通路因子的磷酸化来减轻UC相关IF，从而抑制成纤维细胞活化和胶原沉积。本研究为HYY在UC相关IF管理中的作用机制提供了新的见解。
