Abstract
Magnolol (MG) is a kind of lignin isolated from Magnolia officinalis, 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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is defined by the presence of hepatic steatosis, or the accumulation of excessive fat deposition in liver cells, which is often related to insulin resistance, chronic over-nutrition, and metabolic syndrome [1]
Cells were treated with inhibitors of AKT (LY294005) and AMPK, and the results demonstrated that these inhibitors blocked peroxisome proliferator-activated receptor α (PPARα) protein expression (Figures 4H–N)
Non-alcoholic fatty liver disease often gives rise to hepatic steatosis, which is mostly associated with abnormal lipid metabolism and lipid accumulation [6]
Summary
Non-alcoholic fatty liver disease (NAFLD) is defined by the presence of hepatic steatosis, or the accumulation of excessive fat deposition in liver cells, which is often related to insulin resistance, chronic over-nutrition, and metabolic syndrome [1]. NAFLD is associated with increased incidence of metabolic diseases, such as insulin resistance, type II diabetes, and hypertriglyceridemia. A few years ago, the American Association for the Study of Liver Disease guidelines suggested that only biopsy-proven NASH should be applied for medical treatment, but there are currently no other approved treatments for NAFLD except for losing weight through diet and exercise [4]. In 2017, there are no approved drug treatments for NAFLD and NASH [5]. Finding an agent that can protect against hepatic steatosis may be a feasible strategy to treat NAFLD [6]
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