Fumigaclavine C improves concanavalin A-induced liver injury in mice mainly via inhibiting TNF-alpha production and lymphocyte adhesion to extracellular matrices.
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.
Zhao
Ying
Y
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
Liu
Junyan
J
Wang
Jun
J
Wang
Lei
L
Yin
Hao
H
Tan
Renxiang
R
Xu
Qiang
Q
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*
D000470:Alkaloids; D004876:Ergot Alkaloids; D026121:Indole Alkaloids; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; C492995:fumigaclavine C; D003208:Concanavalin A