Inhibitor Effect Of Liposomal Quercetin On Hepatic Fibrosis Induced By Concanavalin A

Background: Hepatic fibrosis is a common sequel to a variety of liver diseases of varying causes, to date, there are few therapeutic strategies for treating liver fibrosis and liver cirrhosis. Autoimmune response play an important role in the progress of hepatic fibrosis. Quercetin (3,3,4,5,7-pentahydroxy flavone) is a flavonoid phytoestrogen abundantly presented in vegetables, and fruits and the effect of quercetin on inflammatory response has been invested in some in vivo and in vitro studies. However, the clinical application of quercetin was limited by its poor solubility, short half-life time in the plasma, and high dose administration. In this paper, quercetin was encapsulated with PEG-PE liposome to improve its poorly insolubility and the inhibitions of liposomal quercetin on acute hepatitis and hepatic fibrosis induced by concanavalin A were investigated. The goal was to explore whether liposomal quercetin can be a potent clinical therapeutic strategy in the treatment of acute hepatitis and hepatic fibrosis. And the expression levels of NF-κB and TGF-β1 were analysed using immunohistochemistry and real-time RT-PCR.Methods. Hepatic fibrosis was induced by 6 weekly intravenous injections of Con A, and PEG-PE liposomal quercetin were treated intraperitoneally. Mice were sacrificed 1 week after the sixth Con A injection, H&E and Masson Trichrome stainning were performed and the expression levels of NF-κB and TGF-β1 were analysed using immunohistochemistry and real-time RT-PCR.Results. H&E stainning showed that lymphocyte in filtration, fibroblasts hyperplasia and collagen deposition were inhibited by PEG-PE liposomal quercetin treatment. Masson Trichrome stainning showed that less collagen deposition after PEG-PE liposomal quercetin treatment. Light green staining analysis revealed that collagen deposition decreased from 7.36% in mice treated by NS to 1.75% in mice treated with 0.5 mg/kg PEG-PE liposomal quercetin (P＜0.001). And lower expression level of NF-κB and TGF-β1 were detected in mice treated by PEG-PE liposomal quercetin.Conclusion. PEG-PE liposomal quercetin can improved hepatic fibrosis induced by Concanavalin A. Although the underlying mechanism was not completely clear, the present study revealed that the inhibitory effect of PEG-PE liposomal quercetin on hepatic fibrosis is associated with its ability to modulate NF-κB and TGF-β1 production.