title: Inhibitory effect of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A.
abstract: Immune response plays an important role in the development of hepatic fibrosis. In the present study, we investigated the effects of quercetin on hepatitis and hepatic fibrosis induced by immunological mechanism. In the acute hepatitis model, quercetin (2.5 mg/kg) was injected iv into mice 30 min after concanavalin A (Con A) challenge. Mice were sacrificed 4 or 24 h after Con A injection, and aminotransferase tests and histopathological sections were performed. Treatment with quercetin significantly decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Consistent with this observation, treatment with quercetin markedly attenuated the pathologic changes in the liver. A hepatic fibrosis model was also generated in mice by Con A challenge once a week for 6 consecutive weeks. Mice in the experimental group were treated with daily iv injections of quercetin (0.5 mg/kg). Histopathological analyses revealed that treatment with quercetin markedly decreased collagen deposition, pseudolobuli development, and hepatic stellate cells activation. We also examined the effects of quercetin on the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) pathways by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). NF-κB and TGF-β production was decreased after treatment with quercetin, indicating that the antifibrotic effect of quercetin is associated with its ability to modulate NF-κB and TGF-β production. These results suggest that quercetin may be an effective therapeutic strategy in the treatment of patients with liver damage and fibrosis.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: M H
authors.initials: MH
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: X C
authors.initials: XC
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: L J
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Y S
authors.initials: YS
authors.lastname: Wang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001219:Aspartate Aminotransferases / Q000097:blood; D003094:Collagen / Q000032:analysis; D003208:Concanavalin A; D004195:Disease Models, Animal; D005260:Female; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D006505:Hepatitis / Q000188:drug therapy*; D008081:Liposomes; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008807:Mice, Inbred BALB C; D008934:Mitogens; D016328:NF-kappa B / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008081:Liposomes; D008934:Mitogens; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D003094:Collagen; D011794:Quercetin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
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