{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:01:59Z","timestamp":1791720119613,"version":"4.3.4"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:p>The central purpose of this study was to investigate therapeutic effects of the botanical derivative, kinsenoside (KD), in experimental autoimmune hepatitis (AIH). Treatment with KD substantially reduced hepatic histopathological damage, induced by lymphocyte infiltration and proinflammatory cytokines, in concanavalin A\u2010induced T\u2010cell\u2010mediated hepatitis, and in dendritic cells (DCs) loaded with hepatocellular carcinoma cells (DC\/Hepa1\u20106) induced murine AIH. Interactions between immune cells after KD treatment in AIH were detected by anti\u2010CD8 antibody blocking, CD8<jats:sup>+<\/jats:sup>T cell sorting, and vaccinated mice with KD\u2010pretreated DCs in a DC\/Hepa1\u20106 model. These results showed that KD inhibited the elevated expressions of CD86 and major histocompatibility complex II, densities of chemokine receptor C\u2010C chemokine receptor type 7, and extensive migration to lymph nodes, and increased the programmed death ligand 1 level of DCs, followed by suppressing CD8<jats:sup>+<\/jats:sup>T cells, characterized as low differentiation and cytotoxicity, and eliciting cytokines balance. Furthermore, biochemical analysis, two\u2010dimensional fingerprint screen and three\u2010dimensional molecular docking results showed that KD bound to the vascular endothelial growth factor receptor 2 (VEGFR2) kinase domain, which inhibited the metabolism\u2010related phosphatidylinositol 3 kinase\/protein kinase B (PI3K\u2010AKT) pathway in DCs and DC\u2010modulated CD8<jats:sup>+<\/jats:sup>T cells to lower the mitochondrial membrane potential and glucose\/lipid utilization ratio in both cells. KD reversed activation of the PI3K\u2010AKT pathway by 740 Y\u2010P (PI3K agonist), thereby impeding the translocation and dimerization of signal transducer and activators of transcription (STAT) 3 and synergistically blocking the inflammation\u2010related Janus kinase (JAK) 2\/STAT3 pathway in DCs and DC\u2010modulated T cells.<jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: KD treatment elicits immunosuppression against autoimmune liver injury by targeting VEGFR2, followed by diminishing the cross\u2010talk of metabolism\u2010related PI3K\u2010AKT and inflammation\u2010related JAK2\u2010STAT3 pathways, and thereby disrupts DC\u2010induced cross\u2010priming of CD8<jats:sup>+<\/jats:sup>T cell responses. (H<jats:sc>epatology<\/jats:sc>2016;64:2135\u20102150).<\/jats:p>","DOI":"10.1002\/hep.28825","type":"journal-article","created":{"date-parts":[[2016,9,17]],"date-time":"2016-09-17T15:19:00Z","timestamp":1474125540000},"page":"2135-2150","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":53,"title":["Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells\/CD8+T cells communication in mice"],"prefix":"10.1097","volume":"64","author":[{"given":"Ming","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Tongji Medical College,Huazhong University of Science and 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