{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:45:07Z","timestamp":1788983107020,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer (CRC) is intricately linked to gut microbiota dysbiosis and tryptophan (Trp) metabolic dysregulation. This study aimed to clarify the role and mechanisms of 20(S\/R)-ginsenoside Rh1 in suppressing colorectal cancer through the regulation of gut microbiota and Trp metabolism. Azoxymethane\/dextran sulfate sodium (AOM\/DSS)was employed to induce a CRC mouse model, followed by treatment with 20(S\/R)-ginsenoside Rh1 at 100 mg\u00b7kg\u22121\u00b7day\u22121 for 6 weeks. 20(S\/R)-ginsenoside Rh1 significantly reduced the disease activity index (DAI) score, restored colon length, and decreased tumor count. 20(S\/R)-Ginsenoside Rh1 ameliorated gut dysbiosis by increasing gut microbial diversity and elevating the prevalence of beneficial bacteria, including Lactobacillus, and stimulated the production of indole derivatives, including indole-3-propionic acid (IPA), indole-3-acetic acid (IAA), and indole-3-lactic acid (ILA) by enriching Trp -metabolizing bacteria such as Lactobacillus reuteri. These changes further activated the AhR\/CYP1A1\/IL-22 and PXR\/TLR4 pathways, upregulated the expression of intestinal tight junction proteins, suppressed the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-\u03b1), interleukin-6 (IL-6), and IFN-\u03b3, and elevated the levels of the anti-inflammatory cytokine IL-10. Furthermore, 20(S\/R)-ginsenoside Rh1 reduces the serum kynurenine (Kyn)\/Trp ratio, downregulates the expression of forkhead box P3 (FoxP3), a marker of regulatory T (Treg) cells, and increases the number of CD8+ T cells by inhibiting the expression of indoleamine 2,3-dioxygenase 1 (IDO1) in colonic tissue. In conclusion, 20(S\/R)-ginsenoside Rh1 showed potential anti-CRC activity, with our study observing links between its action and gut microbiota structure regulation, Trp metabolism modulation, AhR\/PXR-mediated intestinal barrier activation, and IDO1-related immune suppression reversal.<\/jats:p>","DOI":"10.3390\/ijms27125477","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:11:22Z","timestamp":1781709082000},"page":"5477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["20(S\/R)-Ginsenoside Rh1 Alleviates AOM\/DSS-Induced Colorectal Cancer: Gut-Microbiota Modulation and Tryptophan-Metabolism-Mediated AhR\/PXR Activation and IDO1"],"prefix":"10.3390","volume":"27","author":[{"given":"Linqian","family":"Lu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyu","family":"Min","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yansong","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6140-3423","authenticated-orcid":false,"given":"Zijian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Kang","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-617X","authenticated-orcid":false,"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4305-6306","authenticated-orcid":false,"given":"Shengyu","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun 130033, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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