Aegle marmelos effectively attenuates DSS-induced colitis by restoring intestinal mucosal barrier and alleviating inflammation through modulation of gut microbiota in mice.

BACKGROUND

In Ayurveda, Aegle marmelos fruit is described for its utility in alleviating gastrointestinal disorders due to its astringent, digestive, and stomachic properties.

PURPOSE: Here the aim was to explore the mechanism involved in the protective effect of A. marmelos against ulcerative colitis (UC) in murine model. The study also compared the anti-colitis efficacy of two distinct fruit morphotypes of A. marmelos available in India (oblate-spheroid, Lucknow; pyriform, Bengaluru). Further, it explored the role of the more effective one in modulating the gut microbiota in mice.

STUDY

DESIGN

Aqueous, ethanolic and hydroalcoholic extracts of A. marmelos fruit were analyzed for efficacy against dextran sulfate sodium (DSS)-induced UC in mice at 200 mg/kg BW oral dose.

METHODS

The most efficacious extract was subjected to dose-dependent (100-500 mg/kg BW) analysis. Its best dose was analyzed in terms of restoration of cytokine levels, tight junction proteins, intestinal permeability, myeloperoxidase activity, transcript abundance of key genes and modulation of gut microbiota through NGS-based 16S rRNA analysis.

RESULTS

The aqueous extract of Lucknow fruit at 300 mg/kg BW (AM) ameliorated colitis symptoms in DSS-induced mice. It elevated relative abundance of Lactobacillus and Blautia but decreased that of Escherichia-Shigella, Clostridium sensu stricto 1 and Romboutsia in the gut microbiota. AM downregulated Tlr4 transcripts, upregulated Muc2 and Slc6a4 transcripts, ZO-1 protein and goblet cells in colon showing barrier protective properties against colon damage and inflammatory response. Moreover, it was found to be safe up to 3000 mg/kg BW.

CONCLUSION

This study has elucidated the potential of A. marmelos treatment in UC by modulation of gut microbiome and provided strong scientific evidence to validate its use in traditional medicine.