Abstract
Magnolol (MG) is the main active compound of Magnolia officinalis and exerts a wide range of biological activities. In this study, we investigated the effects of MG using tyloxapol (Tylo)-induced (200 mg/kg, i.p.) hyperlipidemia in rats and palmitic acid (PA)-stimulated (0.3 mM) HepG2 cells. Our results showed that Tylo injection significantly increased plasma levels of triglyceride and cholesterol as well as superoxide anion in the livers, whereas MG pretreatment reversed these changes. MG reduced hepatic lipogenesis by attenuating sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) proteins and Srebp-1, Fas, Acc, and Cd36 mRNA expression as well as upregulated the lipolysis-associated genes Hsl, Mgl, and Atgl. Furthermore, MG reduced plasma interleukin-1β (IL-1β) and protein expression of NLR family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and caspase 1 as well as upregulated nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and induction of heme oxygenase-1 (HO-1) in hepatocytes of Tylo-treated rats. Enhanced autophagic flux by elevation of autophagy related protein 5-12 (ATG5-12), ATG7, Beclin1, and microtubule-associated protein light chain 3 B II (LC3BII)/LC3BI ratio, and reduction of sequestosome-1 (SQSTM1/p62) and phosphorylation of mTOR was observed by MG administration. However, autophagy inhibition with 3-methyladenine (3-MA) in HepG2 cells drastically abrogated the MG-mediated suppression of inflammation and lipid metabolism. In conclusion, MG inhibited hepatic steatosis-induced NLRP3 inflammasome activation through the restoration of autophagy to promote HO-1 signaling capable of ameliorating oxidative stress and inflammatory responses.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, with the prevalence ranging from 25% to 45% [1] and characterized by excessive lipid accumulationAntioxidants 2020, 9, 924; doi:10.3390/antiox9100924 www.mdpi.com/journal/antioxidantsAntioxidants 2020, 9, 924 in the hepatocytes
NAFLD is characterized by the accumulation of lipid droplets in hepatocytes and hyperlipidemia, NAFLD is characterized by the accumulation of lipid droplets in hepatocytes and which results in systemic inflammatory responses and metabolic abnormalities
We showed that MG administration increased the expression of heme oxygenase-1 (HO-1) and SOD2 by promoting the translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus
Summary
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, with the prevalence ranging from 25% to 45% [1] and characterized by excessive lipid accumulationAntioxidants 2020, 9, 924; doi:10.3390/antiox9100924 www.mdpi.com/journal/antioxidantsAntioxidants 2020, 9, 924 in the hepatocytes. Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, with the prevalence ranging from 25% to 45% [1] and characterized by excessive lipid accumulation. The pathogenesis includes a broad spectrum of hepatic changes such as steatosis, steatohepatitis, and cirrhosis [2]. Inflammatory disorders, and oxidative stress are the main risk factors in the pathological changes of NAFLD [3,4]. The development of new therapeutic strategies capable of improving the pathogenesis of NAFLD warrants urgent exploration. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates antioxidant machinery and expresses a variety of antioxidant genes, including heme oxygenase-1 (HO-1) and superoxide dismutase
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
