Corilagin Alleviates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced C57BL/6 Mice by Ameliorating Oxidative Stress and Restoring Autophagic Flux

Frontiers in Pharmacology

Lina Ma¹  Jingjing Wu¹  Xia Chen²  Rong Zhang³  Chenfang Zhu⁴  Kexin Chu⁵  Nengjiang Zhao⁶  Mingjuan Liao⁷  Gang Wei⁸ 

[1] Department of Breast, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;Department of Endocrinology and Metabolism, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China;Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Department of General Surgery, The Ninth People’s Hospital, Medical School of Shanghai Jiaotong University, Shanghai, China;Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China;Department of Traditional Chinese Medicine Studio, The First Affiliated Hospital of Xiamen University, Xiamen, China;Department of Traditional Chinese Medicine, The Ninth People’s Hospital, Medical School of Shanghai Jiaotong University, Shanghai, China;Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China;

关键词: Corilagin;    nonalcoholic fatty liver disease;    autophagy;    oxidative stress;    mitochondrial dysfunction;   

DOI  :  10.3389/fphar.2019.01693

来源: DOAJ

【 摘 要 】

Corilagin (Cori) possesses multiple biological activities. To determine whether Cori can exert protective effects against nonalcoholic fatty liver disease (NAFLD) and its potential mechanisms. C57BL/6 mice were fed with high-fat diet (HFD) alone or in combination with Cori (20 mg/kg, i.p.) and AML12 cells were exposed to 200 μM PA/OA with or without Cori (10 μM or 20 μM). Phenotypes and key indicators relevant to NAFLD were examined both in vivo and in vitro. In this study, Cori significantly ameliorated hepatic steatosis, confirmed by improved serum lipid profiles, and hepatic TC, TG contents, and the gene expression related to lipid metabolism in livers of HFD mice. Moreover, Cori attenuated HFD-mediated autophagy (including mitophagy) blockage by restoring autophagic flux, evidenced by increased number of autophagic double vesicles containing mitochondria, elevated LC3II protein levels, decreased p62 protein levels, as well as enhanced colocalization of autophagy-related protein (LC3, Parkin) and mitochondria. In accordance with this, Cori also reduced the accumulation of ROS and MDA levels, and enhanced the activities of antioxidative enzymes including SOD, GSH-Px, and CAT. In addition, Cori treatment improved mitochondrial dysfunction, evidenced by increased mitochondrial membrane potential (ΔΨm). In parallel with this, Cori decreased mitochondrial DNA oxidative damage, while increased mitochondrial biogenesis related transcription factors expression, mitochondrial DNA content and oxygen consumption rate (OCR). In conclusion, these results demonstrate that Cori is a potential candidate for the treatment of NAFLD via diminishing oxidative stress, restoring autophagic flux, as well as improving mitochondrial functions.

【 授权许可】

Unknown