title: Silymarin alleviates hepatic oxidative stress and protects against metabolic disorders in high-fat diet-fed mice.
abstract: Silymarin is a potent antioxidant medicine and has been widely used for the treatment of liver diseases over 30 years. Recent studies suggest that silymarin may benefit patients with glucose intolerance. However, the mechanism underlying the action of silymarin is not clarified. The aim of this work was to assess the impact of silymarin on glucose intolerance in high-fat diet (HFD)-fed mice, and explore the potential therapeutic mechanisms. C57BL/6 mice were fed with HFD for 12 weeks, randomized, and treated orally with vehicle saline or silymarin (30 mg/kg) daily for 30 days. We found that silymarin significantly improved HFD-induced body weight gain, glucose intolerance, and insulin resistance in mice. Silymarin treatment reduced HFD-increased oxidative stress indicators (reactive oxygen species, lipid peroxidation, protein oxidation) and restored HFD-down-regulated activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in the plasma and/or liver of the HFD-fed mice. Furthermore, silymarin decreased HFD-up-regulated hepatic NADPH oxidase expression and NF-κB activation in mice. Additionally, silymarin treatment mitigated HFD-increased plasma IL-1β, TNF-α levels, and HFD-enhanced hepatic NO, TLR4, and iNOS expression in mice. These novel data indicate that silymarin has potent anti-diabetic actions through alleviating oxidative stress and inflammatory response, partially by inhibiting hepatic NADPH oxidase expression and the NF-κB signaling.
authors.affiliation: a Department of Endocrinology , Nanjing Drum Tower Hospital, Nanjing University School of Medicine , Nanjing , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.affiliation: a Department of Endocrinology , Nanjing Drum Tower Hospital, Nanjing University School of Medicine , Nanjing , China.
authors.forename: Ran
authors.initials: R
authors.lastname: Meng
authors.affiliation: a Department of Endocrinology , Nanjing Drum Tower Hospital, Nanjing University School of Medicine , Nanjing , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: a Department of Endocrinology , Nanjing Drum Tower Hospital, Nanjing University School of Medicine , Nanjing , China.
authors.forename: Shanmei
authors.initials: S
authors.lastname: Shen
authors.affiliation: a Department of Endocrinology , Nanjing Drum Tower Hospital, Nanjing University School of Medicine , Nanjing , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bi
authors.affiliation: a Department of Endocrinology , Nanjing Drum Tower Hospital, Nanjing University School of Medicine , Nanjing , China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002374:Catalase / Q000187:drug effects / Q000235:genetics; D059305:Diet, High-Fat; D018149:Glucose Intolerance / Q000188:drug therapy*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000187:drug effects / Q000235:genetics; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D012838:Silymarin / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D007004:Hypoglycemic Agents; D016328:NF-kappa B; D012838:Silymarin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases
keywords: Antioxidant status; NF-κB pathway; hepatic injury; metabolic disorder; obesity