{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:37:19Z","timestamp":1790361439139,"version":"4.1.0"},"reference-count":41,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32201393"],"award-info":[{"award-number":["32201393"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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-\u03baB, 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.<\/jats:p>","DOI":"10.1021\/acs.jafc.5c17587","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:19:29Z","timestamp":1785849569000},"page":"24277-24291","source":"Crossref","is-referenced-by-count":1,"title":["Microbiota-Mediated Conversion of Asiaticoside to\nAsiatic Acid Restores Intestinal Homeostasis in Mice with Chronic\nIntestinal Inflammation"],"prefix":"10.1021","volume":"74","author":[{"given":"Yuwei","family":"Wu","sequence":"first","affiliation":[{"name":"Tianjin University of Technology , , ,","place":["Tianjin, China, 300384"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Tianjin First Central Hospital , , ,","place":["Tianjin, China, 300192"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1618-9728","authenticated-orcid":true,"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin University of Technology , , ,","place":["Tianjin, China, 300384"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Tang","family":"Ho","sequence":"additional","affiliation":[{"name":"Rutgers University , , , ,","place":["New Brunswick, New Jersey, United States, 08901"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"2026081208095938300_cit1","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1053\/j.gastro.2025.08.040","article-title":"Fecal detection of calprotectin subunits links inflammatory\nbowel disease activity with chronicity of intestinal inflammation","volume":"170","author":"Jukic","year":"2026","journal-title":"Gastroenterology"},{"key":"2026081208095938300_cit2","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1053\/j.gastro.2025.09.030","article-title":"Epidemiology, natural history, and treatment of eosinophilic\ngastrointestinal diseases","volume":"170","author":"Visaggi","year":"2026","journal-title":"Gastroenterology"},{"issue":"10","key":"2026081208095938300_cit3","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1016\/j.cgh.2024.08.040","article-title":"No impact of concomitant medications\non efficacy and safety of biologics and small molecules for ulcerative\ncolitis","volume":"23","author":"Ahuja","year":"2025","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"4","key":"2026081208095938300_cit4","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/S2468-1253(19)30048-2","article-title":"Microscopic colitis: Pathophysiology and clinical management","volume":"4","author":"Miehlke","year":"2019","journal-title":"Lancet Gastroenterol. 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Zhejiang Univ., Sci., B"},{"issue":"6775","key":"2026081208095938300_cit7","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1126\/science.aec7924","article-title":"A bacterial toxin disarms\ngut defenses against inflammation","volume":"390","author":"Modilevsky","year":"2025","journal-title":"Science"},{"issue":"6775","key":"2026081208095938300_cit8","doi-asserted-by":"publisher","DOI":"10.1126\/science.adz4712","article-title":"An Aeromonas variant that produces aerolysin promotes\nsusceptibility to ulcerative colitis","volume":"390","author":"Jiang","year":"2025","journal-title":"Science"},{"issue":"1","key":"2026081208095938300_cit9","doi-asserted-by":"publisher","first-page":"2596405","DOI":"10.1080\/19490976.2025.2596405","article-title":"Bidirectional microbial\nregulation by tyrosine metabolism enhances palmatine-mediated colitis\nprotection","volume":"17","author":"Sun","year":"2025","journal-title":"Gut Microbes"},{"issue":"1","key":"2026081208095938300_cit10","doi-asserted-by":"publisher","first-page":"2581445","DOI":"10.1080\/19490976.2025.2581445","article-title":"Cross-species engraftment\nbiases and metabolic divergence in gnotobiotic mice humanized with\nulcerative colitis microbiota","volume":"17","author":"Guggeis","year":"2025","journal-title":"Gut Microbes"},{"key":"2026081208095938300_cit11","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202509383","article-title":"Faecalibaculum rodentium\nalleviates ionizing radiation-induced damage\nin mice by improving intestinal integrity and hematopoiesis via its\nmetabolite butyrate","volume":"13","author":"Zhu","year":"2026","journal-title":"Adv. Sci."},{"issue":"1","key":"2026081208095938300_cit12","doi-asserted-by":"publisher","first-page":"2545414","DOI":"10.1080\/19490976.2025.2545414","article-title":"Acute effects\nof butyrate on intestinal permeability in patients with irritable\nbowel syndrome assessed by a novel colonoscopy research model","volume":"17","author":"Scharf","year":"2025","journal-title":"Gut Microbes"},{"key":"2026081208095938300_cit13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.11.045","article-title":"Tripterygium wilfordii\nmulti-glycoside alleviates ankylosing spondylitis via gut microbiota\nmodulation and metabolite reprogramming","author":"Bi","year":"2025","journal-title":"J.\nAdv. 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Polym."},{"key":"2026081208095938300_cit19","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.jare.2024.12.032","article-title":"Adiponectin deficiency prevents chronic colitis-associated colonic\nfibrosis via inhibiting CXCL13 production","volume":"76","author":"Xiao","year":"2025","journal-title":"J.\nAdv. Res."},{"issue":"47","key":"2026081208095938300_cit20","doi-asserted-by":"publisher","first-page":"30236","DOI":"10.1021\/acs.jafc.5c07829","article-title":"Tamarind seed-derived xyloglucan\nattenuates insulin resistance in mice through gut microbiota","volume":"73","author":"Yang","year":"2025","journal-title":"J. Agric. 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Commun."},{"issue":"7","key":"2026081208095938300_cit38","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.3390\/nu13072448","article-title":"Immunomodulatory\nand anti-inflammatory effects of asiatic acid in a DNCB-induced atopic\ndermatitis animal model","volume":"13","author":"Moon","year":"2021","journal-title":"Nutrients"},{"issue":"1","key":"2026081208095938300_cit39","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s40168-021-01115-9","article-title":"Gut microbiota from\ngreen tea polyphenol-dosed mice\nimproves intestinal epithelial homeostasis and ameliorates experimental\ncolitis","volume":"9","author":"Wu","year":"2021","journal-title":"Microbiome"},{"issue":"5","key":"2026081208095938300_cit40","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.cmet.2011.02.018","article-title":"The microbiome and\nbutyrate regulate\nenergy metabolism and autophagy in the mammalian colon","volume":"13","author":"Donohoe","year":"2011","journal-title":"Cell Metab."},{"issue":"1","key":"2026081208095938300_cit41","doi-asserted-by":"publisher","first-page":"2307542","DOI":"10.1080\/19490976.2024.2307542","article-title":"Gut microbiota modulate CD8 + T cell immunity in gastric\ncancer through Butyrate\/GPR109A\/HOPX","volume":"16","author":"Yu","year":"2024","journal-title":"Gut Microbes"}],"container-title":["Journal of Agricultural and Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.5c17587","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/31\/24277\/66334064\/acs.jafc.5c17587.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/31\/24277\/66334064\/acs.jafc.5c17587.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:22:02Z","timestamp":1786537322000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/31\/24277\/5236979\/Microbiota-Mediated-Conversion-of-Asiaticoside-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":41,"journal-issue":{"issue":"31","published-online":{"date-parts":[[2026,7,30]]},"published-print":{"date-parts":[[2026,8,12]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.5c17587","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}