Microbiota-Mediated Conversion of Asiaticoside to Asiatic Acid Restores Intestinal Homeostasis in Mice with Chronic Intestinal Inflammation.

Authors

Yuwei Wu, Meiqi Zhao, Peng Zhang, Chi-Tang Ho

Published in

Journal of agricultural and food chemistry. Volume 74. Issue 31. Pages 24277-24291. Aug 12, 2026.

Abstract

Asiaticoside, a triterpenoid saponin abundant in Centella asiatica, exhibits notable anti-inflammatory activity but suffers from poor oral bioavailability. Here, we reveal a gut microbiota-dependent mechanism underlying its therapeutic efficacy against chronic intestinal inflammation. Using a DSS-induced mouse model and antibiotic-mediated microbiota depletion, we demonstrate that asiaticoside requires microbial metabolism to alleviate epithelial injury, oxidative stress, and inflammatory cytokine production. HPLC analysis showed that asiaticoside is hydrolyzed by gut microbes into asiatic acid, which accumulates in colonic tissues and suppresses IL-17 signaling, NF-κB, and JAK2/STAT3 activation while restoring Nrf2-mediated antioxidant responses. The released glycosides are further fermented into butyrate and other short-chain fatty acids, supporting colonocyte metabolism and intestinal barrier function. Antibiotic treatment abolishes asiaticoside conversion, SCFA production, and therapeutic efficacy. These findings establish microbial biotransformation as a critical determinant of asiaticoside activity and a key mechanism governing natural glycoside pharmacology.

PMID:
42584118
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.

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