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Glycyrrhizin inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis model
Author(s) -
Fu Yunhe,
Zhou Ershun,
Wei Zhengkai,
Liang Dejie,
Wang Wei,
Wang Tiancheng,
Guo Mengyao,
Zhang Naisheng,
Yang Zhengtao
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12801
Subject(s) - glycyrrhizin , chemistry , tumor necrosis factor alpha , lipopolysaccharide , trif , pharmacology , microbiology and biotechnology , in vivo , biology , receptor , toll like receptor , immunology , biochemistry , innate immune system
Glycyrrhizin, a triterpene glycoside isolated from licorice root, is known to have anti‐inflammatory activities. However, the effect of glycyrrhizin on mastitis has not been reported. The purpose of this study was to investigate the anti‐inflammatory effect and mechanism of action of glycyrrhizin on lipopolysaccharide ( LPS )‐induced mastitis in mouse. An LPS ‐induced mouse mastitis model was used to confirm the anti‐inflammatory activity of glycyrrhizin in vivo . Primary mouse mammary epithelial cells were used to investigate the molecular mechanism and targets of glycyrrhizin. In vivo , glycyrrhizin significantly attenuated the mammary gland histopathological changes, myeloperoxidase activity and infiltration of neutrophilic granulocytes and downregulated the expression of tumor necrosis factor‐α, interleukin ( IL )‐1β and IL ‐6 caused by LPS . In vitro , glycyrrhizin dose‐dependently inhibited the LPS ‐induced expression of tumor necrosis factor‐α, IL ‐6, and RANTES . Western blot analysis showed that glycyrrhizin suppressed LPS ‐induced nuclear factor‐κB and interferon regulatory factor 3 activation. However, glycyrrhizin did not inhibit nuclear factor‐κB and interferon regulatory factor 3 activation induced by MyD88‐dependent (MyD88, IKKβ) or TRIF‐dependent (TRIF, TBK1) downstream signaling components. Moreover, glycyrrhizin did not act though affecting the function of CD 14 or expression of Toll‐like receptor 4. Finally, we showed that glycyrrhizin decreased the levels of cholesterol of lipid rafts and inhibited the translocation of Toll‐like receptor 4 to lipid rafts. Moreover, glycyrrhizin activated ATP ‐binding cassette transporter A1, which could induce cholesterol efflux from lipid rafts. In conclusion, we find that the anti‐inflammatory effects of glycyrrhizin may be attributable to its ability to activate ATP ‐binding cassette transporter A1. Glycyrrhizin might be a useful therapeutic reagent for the treatment of mastitis and other inflammatory diseases.