Magnolol Alleviates Inflammatory Responses and Lipid Accumulation by AMP-Activated Protein Kinase-Dependent Peroxisome Proliferator-Activated Receptor α Activation

• Published in: Frontiers in immunology Vol. 9; p. 147
• Main Authors: Tian, Ye, Feng, Haihua, Han, Lu, Wu, Lin, Lv, Hongming, Shen, Bingyu, Li, Zheng, Zhang, Qiaoling, Liu, Guowen
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 05.02.2018
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biphenyl Compounds - pharmacology; Biphenyl Compounds - therapeutic use; Fatty Liver - chemically induced; Fatty Liver - drug therapy; Fatty Liver - metabolism; Hep G2 Cells; Humans; hyperlipidemia; Hyperlipidemias - chemically induced; Hyperlipidemias - drug therapy; Hyperlipidemias - metabolism; Immunology; inflammatory responses; Lignans - pharmacology; Lignans - therapeutic use; Lipid Metabolism - drug effects; magnolol; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; Oleic Acid; peroxisome proliferator-activated receptor α; PPAR alpha - metabolism; steatosis; AMPK; hyperlipidemia; inflammatory responses; magnolol; steatosis; peroxisome proliferator-activated receptor α
• DOI: 10.3389/fimmu.2018.00147
• ISSN: 1664-3224

Magnolol (MG) is a kind of lignin isolated from , which serves several different biological functions, such as antifungal, anticancer, antioxidant, and hepatoprotective functions. This study aimed to evaluate the protective effect of MG against oleic acid (OA)-induced hepatic steatosis and inflammatory damage in HepG2 cells and in a tyloxapol (Ty)-induced hyperlipidemia mouse model. Our findings indicated that MG can effectively inhibit OA-stimulated tumor necrosis factor α (TNF-α) secretion, reactive oxygen species generation, and triglyceride (TG) accumulation. Further study manifested that MG significantly suppressed OA-activated mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways and that these inflammatory responses can be negated by pretreatment with inhibitors of extracellular regulated protein kinase and c-Jun N-terminal kinase (U0126 and SP600125, respectively). In addition, MG dramatically upregulated peroxisome proliferator-activated receptor α (PPARα) translocation and reduced sterol regulatory element-binding protein 1c (SREBP-1c) protein synthesis and excretion, both of which are dependent upon the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), acetyl-CoA carboxylase, and AKT kinase (AKT). However, MG suspended the activation of PPARα expression and was thus blocked by pretreatment with LY294002 and compound c (specific inhibitors of AKT and AMPK). Furthermore, MG clearly alleviated serum TG and total cholesterol release; upregulated AKT, AMPK, and PPARα expression; suppressed SREBP-1c generation; and alleviated hepatic steatosis and dyslipidemia in Ty-induced hyperlipidemia mice. Taken together, these results suggest that MG exerts protective effects against steatosis, hyperlipidemia, and the underlying mechanism, which may be closely associated with AKT/AMPK/PPARα activation and MAPK/NF-κB/SREBP-1c inhibition.