title: Silymarin Ameliorates Metabolic Dysfunction Associated with Diet-Induced Obesity via Activation of Farnesyl X Receptor.
abstract: Background and purpose:Silymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis, and other types of toxic liver damage. Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemiain vitroandin vivo, the mechanism underlying silymarin action remains unclear.Experimental approach:C57BL/6 mice were fed high-fat diet (HFD) for 3 months to induce obesity, insulin resistance, hyperlipidaemia, and fatty liver. These mice were then continuously treated with HFD alone or mixed with silymarin at 40 mg/100 g for additional 6 weeks. Biochemical analysis was used to test the serum lipid and bile acid profiles. Farnesyl X receptor (FXR) and nuclear factor kappa B (NF-κB) transactivities were analyzed in liver using a gene reporter assay based on quantitative RT-PCR.Key results:Silymarin treatment ameliorated insulin resistance, dyslipidaemia and inflammation, and reconstituted the bile acid pool in liver of diet-induced obesity. Associated with this, silybin and silymarin enhanced FXR transactivity. Consistently, in HepG2 cells, silybin inhibited NF-κB signaling, which was enhanced by FXR activation.Conclusion and implications:Our results suggest that silybin is an effective component of silymarin for treating metabolic syndrome by stimulating FXR signaling.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: School of Chemical and Environmental Engineering, Shanghai Institute of Technology Shanghai, China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese MedicineShanghai, China; Brown Foundation Institute of Molecular Medicine and Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical SchoolHouston, TX, USA.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Ma
authors.affiliation: Brown Foundation Institute of Molecular Medicine and Program in Neuroscience, Graduate School of Biological Sciences, University of Texas McGovern Medical School Houston, TX, USA.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Research Centre for Traditional Chinese Medicine of Complexity Systems, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
keywords: farnesyl X receptor; metabolic syndrome; non-alcoholic fatty liver disease; silybin; silymarin