Cai Ya-Jie, Lan Jian-Hang, Li Shuo, Feng Yue-Ning, Li Fang-Hong, Guo Meng-Yu, Liu Run-Ping
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
Department of Proctology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China.
J Integr Med. 2025 Jul;23(4):429-444. doi: 10.1016/j.joim.2025.06.004. Epub 2025 Jun 14.
Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery.
Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis.
SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as Irf7, Pparα, Clspn and Hspa5. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach.
Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis. Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429-444.
溃疡性结肠炎与肠干细胞（ISC）丢失及肠道黏液屏障受损密切相关。四逆散（SNS）是一种复方中药，在治疗肠道功能障碍方面有着悠久的历史，但SNS是否能通过调节ISC增殖和分泌细胞分化来缓解急性实验性结肠炎尚未见研究报道。本研究检测了SNS对急性结肠炎的影响，并着重探讨其涉及肠道屏障恢复的机制。
采用SNS的网络药理学分析和入血成分分析，以探究SNS影响急性葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎模型的潜在机制。利用RNA测序来阐明该机制。此外，在体内及结肠类器官中进行逆转录定量聚合酶链反应、免疫荧光染色以及阿尔辛蓝和过碘酸希夫染色，以研究SNS与细胞谱系分化相关的机制。此外，通过网络药理学分析预测SNS的潜在活性成分。
SNS显著抑制DSS诱导的小鼠急性结肠炎症。RNA测序分析显示，炎症和凋亡相关基因表达下调，脂质代谢和增殖相关基因如Irf7、Pparα、Clspn和Hspa5表达上调。此外，SNS在体内及体外结肠类器官中均显著促进ISC更新和肠道分泌细胞谱系定向分化，从而导致黏蛋白表达增加。此外，采用网络药理学方法预测了SNS中介导炎症、脂质代谢及增殖、凋亡、干细胞和分泌细胞的潜在活性成分。
本研究从ISC更新和分泌谱系细胞分化的角度阐明了SNS减轻急性结肠炎的潜在机制，提示了一种治疗结肠炎的新策略。请引用本文：Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429 - 444.
