期刊文献+

S-Allylmercaptocysteine improves alcoholic liver disease partly through a direct modulation of insulin receptor signaling 被引量:6

原文传递
导出
摘要 Alcoholic liver disease(ALD) causes insulin resistance, lipid metabolism dysfunction, and inflammation. We investigated the protective effects and direct regulating target of S-allylmercaptocysteine(SAMC) from aged garlic on liver cell injury. A chronic ethanol-fed ALD in vivo model(the NIAAA model) was used to test the protective functions of SAMC. It was observed that SAMC(300 mg/kg, by gavage method) effectively ameliorated ALD-induced body weight reduction, steatosis,insulin resistance, and inflammation without affecting the health status of the control mice, as demonstrated by histological, biochemical, and molecular biology assays. By using biophysical assays and molecular docking, we demonstrated that SAMC directly targeted insulin receptor(INSR) protein on the cell membrane and then restored downstream IRS-1/AKT/GSK3 b signaling. Liver-specific knock-down in mice and siRNA-mediated knock-down in AML-12 cells of Insr significantly impaired SAMC(250 mmol/L in cells)-mediated protection. Restoration of the IRS-1/AKT signaling partly recovered hepatic injury and further contributed to SAMC’s beneficial effects. Continuous administration of AKT agonist and recombinant IGF-1 in combination with SAMC showed hepato-protection in the mice model.Long-term(90-day) administration of SAMC had no obvious adverse effect on healthy mice. We conclude that SAMC is an effective and safe hepato-protective complimentary agent against ALD partly through the direct binding of INSR and partial regulation of the IRS-1/AKT/GSK3 b pathway.
出处 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2021年第3期668-679,共12页 药学学报(英文版)
基金 supported by National Natural Science Foundation of China (81970515) Guangdong Natural Science Funds for Distinguished Young Scholar (2019B151502013, China)。
  • 相关文献

参考文献2

二级参考文献27

  • 1G. Musso,M. Cassader,F. Rosina,R. Gambino.Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials[J]. Diabetologia . 2012 (4)
  • 2Etsuko Hashimoto,Satoru Yatsuji,Maki Tobari,Makiko Taniai,Nobuyuki Torii,Katsutoshi Tokushige,Keiko Shiratori.Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis[J]. Journal of Gastroenterology . 2009 (19)
  • 3Christi A. Matteoni *,Zobair M. Younossi *,Terry Gramlich ?,Navdeep Boparai §,Yao Chang Liu ∥,Arthur J. McCullough ?.Nonalcoholic fatty liver disease: A spectrum of clinical and pathological severity[J]. Gastroenterology . 1999 (6)
  • 4Camilo Boza MD,Arnoldo Riquelme MD,Luis Iba?ez MD,Ignacio Duarte MD,Enrique Norero MD,Paola Viviani MD,Alejandro Soza MD,Jose Ignacio Fernandez MD,Alejandro Raddatz MD,Sergio Guzman MD,Marco Arrese MD.Predictors of Nonalcoholic Steatohepatitis (NASH) in Obese Patients Undergoing Gastric Bypass[J]. Obesity Surgery . 2005 (8)
  • 5Anna Ludovica Fracanzani,Larry Burdick,Sara Raselli,Paola Pedotti,Liliana Grigore,Gennaro Santorelli,Luca Valenti,Alessandra Maraschi,Alberico Catapano,Silvia Fargion.Carotid Artery Intima-media Thickness in Nonalcoholic Fatty Liver Disease[J]. The American Journal of Medicine . 2008 (1)
  • 6Ziya Omer,Sevki Cetinkalp,Murat Akyildiz,Funda Yilmaz,Yucel Batur,Candeger Yilmaz,Ulus Akarca.Efficacy of insulin-sensitizing agents in nonalcoholic fatty liver disease[J]. European Journal of Gastroenterology & Hepatology . 2010 (1)
  • 7John Willy Haukeland,Zbigniew Konopski,Heidi Beate Eggesb?,Hilde L?land von Volkmann,Gabriele Raschpichler,Kristian Bj?ro,Terese Haaland,Else Marit L?berg,K?re Birkeland.Metformin in patients with non-alcoholic fatty liver disease: A randomized, controlled trial[J]. Scandinavian Journal of Gastroenterology . 2009 (7)
  • 8M. J. Armstrong,D. D. Houlihan,I. A. Rowe,W. H. O. Clausen,B. Elbr?nd,S. C. L. Gough,J. W. Tomlinson,P. N. Newsome.Safety and efficacy of liraglutide in patients with type 2 diabetes and elevated liver enzymes: individual patient data meta‐analysis of the LEAD program[J]. Aliment Pharmacol Ther . 2012 (2)
  • 9Zhi-Jiang Zhang,Zhi-Jie Zheng,Rong Shi,Qing Su,Qingwu Jiang,Kevin E. Kip.Metformin for Liver Cancer Prevention in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis[J]. The Journal of Clinical Endocrinology & Metabolism . 2012 (7)
  • 10Suzanne E. Mahady,Angela C. Webster,Sarah Walker,Arun Sanyal,Jacob George.The role of thiazolidinediones in non-alcoholic steatohepatitis – A systematic review and meta analysis[J]. Journal of Hepatology . 2011 (6)

共引文献20

同被引文献42

引证文献6

二级引证文献5

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部