Sishen pill alleviates DSS induced colitis through AGE/RAGE/NLRP3 pathway based on transcriptomics analysis

Area of Science:

• Pharmacology
• Immunology
• Gastroenterology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory colon disorder with significant patient impact.
• Sishen Pill (SSP), a traditional Chinese medicine, has a long history of use for gastrointestinal issues, but its mechanisms in UC are unclear.

Purpose of the Study:

• To investigate the therapeutic efficacy of Sishen Pill (SSP) in a mouse model of ulcerative colitis (UC).
• To elucidate the underlying pharmacological pathways involved in SSP's action against UC.

Main Methods:

• Phytochemical analysis of SSP using UPLC-MS/MS.
• Induction of UC in mice using dextran sulfate sodium (DSS).
• Assessment of clinical, inflammatory, and barrier integrity markers; RNA sequencing and network pharmacology to identify pathways, including AGE-RAGE-NLRP3 axis verification.

Main Results:

• SSP treatment significantly alleviated UC symptoms, including weight loss, colon shortening, and disease activity.
• SSP reduced pro-inflammatory cytokines (IL-6, IL-1β) and increased anti-inflammatory IL-13, restoring intestinal barrier proteins (occludin, claudin-1).
• The AGE-RAGE-NLRP3 axis was identified as the core regulatory pathway, confirmed in vivo and in vitro.

Conclusions:

• Sishen Pill (SSP) demonstrates significant protective effects against ulcerative colitis (UC).
• SSP ameliorates UC by inhibiting the AGEs-RAGE-NLRP3 signaling pathway, highlighting its therapeutic potential.