{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:53:12Z","timestamp":1791175992453,"version":"4.1.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Acute liver injury (ALI) is a severe and prevalent condition that can progress to irreversible liver damage and failure. This study aimed to investigate the prophylactic hepatoprotective potential of\n                    <jats:italic>Silybum marianum<\/jats:italic>\n                    peptides (SMP) in ALI and elucidate its underlying mechanisms. Using a carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )-induced ALI mouse model, we evaluated the dose-dependent effects of SMP. Additionally, we explored the modulatory effects of SMP on the NF-\u03baB pathway, gut microbiota composition, and metabolite profiles. The role of SMP in the TRAF3\/NIK\/NF-\u03baB signaling axis was further validated in a NIK-overexpressing Hepa1-6 cell model. Our results demonstrated that 14-day SMP administration did not significantly affect body weight, fasting blood glucose levels, or liver and spleen weights, and no significant difference in serum ALT activity was observed. Notably, SMP (200\u00a0mg\/kg) significantly alleviated CCl\n                    <jats:sub>4<\/jats:sub>\n                    -induced liver injury, as evidenced by enhanced hepatic antioxidant capacity, reduced expression of proinflammatory cytokines, and attenuated immune cell infiltration. Furthermore, SMP was associated with changes in gut microbiota composition and community structure in CCl\n                    <jats:sub>4<\/jats:sub>\n                    -induced ALI mice. Mechanistically, SMP suppressed the TRAF3\/NIK\/NF-\u03baB pathway. These findings highlight SMP as a promising candidate for the prevention of CCl\n                    <jats:sub>4<\/jats:sub>\n                    -induced ALI, acting through multimodal mechanisms involving anti-inflammatory, antioxidant, and gut microbiota-associated pathways.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1915943","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:34:09Z","timestamp":1791174849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Silybum marianum peptide-rich fraction alleviates acute liver injury by inhibiting TRAF3\/NIK\/NF-\u03baB and is associated with changes in gut microbiota composition"],"prefix":"10.3389","volume":"17","author":[{"family":"Ananda","sequence":"first","affiliation":[{"name":"International School of Mongolian Medicine, Mongolian National University of Medical Sciences","place":["Ulaanbaatar, Mongolia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Han","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, The Second Affiliated Hospital, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khurelbaatar","family":"Nyamdavaa","sequence":"additional","affiliation":[{"name":"International School of Mongolian Medicine, Mongolian National University of Medical Sciences","place":["Ulaanbaatar, Mongolia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Li","sequence":"additional","affiliation":[{"name":"Inner Mongolia Bioactive Peptide Engineering Laboratory, Clinical Medical Research Center, The Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsend-Ayush","family":"Damba","sequence":"additional","affiliation":[{"name":"International School of Mongolian Medicine, Mongolian National University of Medical Sciences","place":["Ulaanbaatar, Mongolia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiulan","family":"Su","sequence":"additional","affiliation":[{"name":"Inner Mongolia Bioactive Peptide Engineering Laboratory, Clinical Medical Research Center, The Affiliated Hospital of Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0144509","DOI":"10.1371\/journal.pone.0144509","article-title":"Free radical-scavenging, anti-inflammatory\/anti-fibrotic and hepatoprotective actions of taurine and silymarin against CCl4 induced rat liver damage","volume":"10","author":"Abdel-Moneim","year":"2015","journal-title":"PloS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5420","DOI":"10.3390\/ijms23105420","article-title":"Green synthesis of silymarin\u2013chitosan nanoparticles as a new nano formulation with enhanced anti-fibrotic effects against liver fibrosis","volume":"23","author":"Abdullah","year":"2022","journal-title":"Int. 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