Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production

Ya-Jie Cai; Jian-Hang Lan; Shuo Li; Yue-Ning Feng; Fang-Hong Li; Meng-Yu Guo; Run-Ping Liu

doi:10.1016/j.joim.2025.06.004

Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production

J Integr Med. 2025 Jun 14:S2095-4964(25)00084-6. doi: 10.1016/j.joim.2025.06.004. Online ahead of print.

Authors

Ya-Jie Cai¹, Jian-Hang Lan¹, Shuo Li¹, Yue-Ning Feng², Fang-Hong Li¹, Meng-Yu Guo³, Run-Ping Liu⁴

Affiliations

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
² Department of Proctology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China.
³ School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
⁴ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: liurunping@bucm.edu.cn.

PMID: 40579337
DOI: 10.1016/j.joim.2025.06.004

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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; Epub ahead of print.

Keywords: Colitis; Intestinal stem cells; Secretory cell lineage; Sinisan.