Intestinal Inflammation Induced by Kai-Xin-San through NF-κB-IL-6 Pathway

doi:10.19803/j.1672-8629.20260134

Abstract

Abstract: Objective To investigate the molecular mechanism through which Kai-Xin-San induces intestinal inflammation in mice in order to ensure its long-term clinical safety. Methods C57BL/6J mice were randomly assigned to the control group and the groups treated with doses of 0.5, 1.0, 2.0 and 4.0 g·kg^-1 before the small intestinal transit rate was determined via an intestinal propulsion test. After 3 or 8 days of administration (The control group and the groups treated with doses of 0.5, 1.0, and 1.5 g·kg^-1), hematological parameters were measured using an automated hematology analyzer. Histopathological injury was examined by hematoxylin and eosin (HE) staining. The expression and distribution of MUC2 were evaluated by immunofluorescence staining. Protein expression levels of NF-κB p65, p-IκB, NLRP3, NLRC4, ASC, and pro-Caspase-1 in intestinal tissues were analyzed by Western blotting. Cytokine levels of IL-1β, TNF-α, IL-6, and IL-22 in the small intestine after 8 days of administration were determined by Luminex multiplex assay while IL-6 levels were measured by ELISA. Results After 3 days of oral Kai-Xin-San administration, the small intestinal transit rate was significantly reduced in a dose-dependent manner. After 8 days of administration, pathological injuries were observed in the jejunum and ileum, including villus atrophy, mucosal architectural disruption, and luminal dilatation. MUC2 fluorescence kept decreasing with the increase in Kai-Xin-San doses. At 1.5 g·kg^-1, Kai-Xin-San markedly upregulated protein expressions of pro-Caspase-1, NF-κB p65, and p-IκB in the small intestine, but no obvious changes were detected in the colon. After 3 days of treatment, these markers did not change significantly in either the small intestine or colon. Luminex and ELISA results both showed a significant increase in IL-6 levels in the 1.5 g·kg^-1dose group. Conclusion Three-day intragastric administration of Kai-Xin-San at 0.5 g·kg^-1 can induce bloating and intestinal dysmotility in mice. Kai-Xin-San may activate the NF-κB pathway, promote IL-6 transcription, and trigger downstream inflammatory responses. The small intestine, particularly the jejunum and ileum, is the principal target organ, suggesting site-specific intestinal toxicity.

Key words: Kai-Xin-San, Intestinal Inflammation, NF-κB, IL-6, Small Intestinal Motility, Mucus Barrier, Mice

CLC Number:

LIU Siyu, YANG Yifei, ZHANG Haijing, ZHANG Guozhuang, GONG Ping, YANG Yun, LIU Ting, XIA Bing. Intestinal Inflammation Induced by Kai-Xin-San through NF-κB-IL-6 Pathway[J]. Chinese Journal of Pharmacovigilance, 2026, 23(5): 519-526.

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URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20260134

https://zgywjj.magtechjournal.com/EN/Y2026/V23/I5/519

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