title: The protective action of scutellarin against immunological liver injury induced by concanavalin A and its effect on pro-inflammatory cytokines in mice.
abstract: Scutellarin is a natural compound from a Chinese herb. The purpose of this paper was to study the protective effect of scutellarin on concanavalin A (Con A)-induced immunological liver injury and its effect on liver nuclear factor kappaB (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and inducible nitric oxide synthase (iNOS) expression in mice. Mouse liver injury was produced by injection of Con A 25 mg kg-1 via the tail vein. Scutellarin 50 or 100 mg kg-1 was peritoneally administered to mice 9 or 1 h before injection of Con A. The levels of serum alanine aminotransferase (ALT) and asparatate aminotransferase (AST), NO2-/NO3- and TNF-alpha were determined with biochemical kits, and ELISA using Quantikine Mouse TNF-alpha kit according the manufacturer's instructions. Liver lesions were examined by light microscope. The expression of TNF-alpha, IFN-gamma, iNOS and Fas mRNA in the livers was detected by RT-PCR; and the expression of c-Fos, c-Jun, iNOS and IkappaB proteins was measured by Western Blotting. As a result, pretreatment with scutellarin 100 mg kg-1 significantly decreased the serum ALT, AST, NO2-/NO3- and TNF-alpha levels, and also reduced liver lesions induced by Con A. Scutellarin 100 mg kg-1 down-regulated expression of TNF-alpha and iNOS mRNA, and c-Fos, c-Jun and iNOS protein, while scutellarin enhanced the degradation of IkappaB in the livers of mice injected with Con A. The results suggest that scutellarin has a protective action against Con A-induced liver injury in mice, and its active mechanism may be related to the inhibition of the NF-kappaB-TNF-alpha-iNOS transduction pathway.
authors.affiliation: Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100050, China.
authors.forename: Zheng Huai
authors.initials: ZH
authors.lastname: Tan
authors.forename: Ling Hong
authors.initials: LH
authors.lastname: Yu
authors.forename: Huai Lin
authors.initials: HL
authors.lastname: Wei
authors.forename: Geng Tao
authors.initials: GT
authors.lastname: Liu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D003208:Concanavalin A; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D005965:Glucuronates / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D005965:Glucuronates; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D009566:Nitrates; D009573:Nitrites; D020011:Protective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D003208:Concanavalin A; D000072000:NF-KappaB Inhibitor alpha; C484876:scutellarin; D047310:Apigenin; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase