title: Fumigaclavine C improves concanavalin A-induced liver injury in mice mainly via inhibiting TNF-alpha production and lymphocyte adhesion to extracellular matrices.
abstract: Fumigaclavine C, an alkaloidal metabolite, was produced by Aspergillus fumigatus (strain No. CY018). This study examined the effect of this compound on concanavalin A (Con A)-induced liver injury in mice, a T cell-dependent model of liver damage. Con A administration resulted in severe liver injury, T lymphocyte activation and a strong increment in spleen cell adhesion, as well as in tumour necrosis factor-alpha (TNF-alpha) production. Against this liver injury, the intraperitoneal administration of fumigaclavine C dose-dependently inhibited the elevation in transaminase activity, TNF-alpha production in serum and the histological changes, including inflammatory infiltration, hepatocyte necrosis and degeneration and Kupffer cell hyperplasia. In addition, this compound in-vitro also inhibited the proliferation of spleen cells induced by Con A, and reduced their IL-2 and TNF-alpha production. Moreover, the intraperitoneal administration of fumigaclavine C inhibited the potential of spleen cells isolated from the liver-injured mice to adhere to fibronectin, laminin and type IV collagen. These results suggest that the improvement of this T cell-mediated liver injury by fumigaclavine C may be related to the inhibition of lymphocyte activation, proliferation and adhesion to extracellular matrices as well as the reduction in TNF-alpha production.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Junyan
authors.initials: J
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
authors.forename: Renxiang
authors.initials: R
authors.lastname: Tan
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001232:Aspergillus fumigatus; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003208:Concanavalin A; D004305:Dose-Response Relationship, Drug; D004876:Ergot Alkaloids; D005109:Extracellular Matrix / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D026121:Indole Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000470:Alkaloids; D004876:Ergot Alkaloids; D026121:Indole Alkaloids; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; C492995:fumigaclavine C; D003208:Concanavalin A