Cepharanthine ameliorates dextran sulphate sodium-induced colitis through modulating gut microbiota

Area of Science:

• Pharmacology
• Microbiology
• Immunology

Background:

• Cepharanthine (CEP), an alkaloid from Stephania Cepharantha Hayata, possesses known anti-inflammatory properties.
• Ulcerative colitis (UC) is a chronic inflammatory bowel disease with complex etiological factors, including gut dysbiosis.

Purpose of the Study:

• To investigate the therapeutic potential of Cepharanthine (CEP) in a DSS-induced mouse model of ulcerative colitis (UC).
• To elucidate the mechanisms underlying CEP's effects on gut microbiota and host inflammatory responses.

Main Methods:

• Induction of UC using dextran sulfate sodium (DSS) in a mouse model.
• Evaluation of CEP's efficacy through 16S rRNA gene sequencing, antibiotic pretreatment, and fecal microbiota transplantation (FMT).
• Integration of transcriptomics and network pharmacology to explore molecular mechanisms.

Main Results:

• CEP treatment significantly ameliorated DSS-induced UC symptoms.
• CEP administration led to a notable reduction in the abundance of specific gut bacteria, including Romboutsia, Turicibacter, and Escherichia-Shigella.
• CEP modulated cytokine and cytokine receptor pathways, with pro-inflammatory hub genes (e.g., CXCL1, CXCL9, CCL7) positively correlated with Romboutsia abundance, identifying it as a potential pathobiont in UC.

Conclusions:

• Cepharanthine (CEP) demonstrates significant efficacy in relieving colon inflammation associated with UC.
• CEP exerts its therapeutic effects by modulating gut microbiota composition and reducing pro-inflammatory cytokine expression.
• CEP represents a promising candidate for developing novel therapeutic strategies for ulcerative colitis.