Berbamine induced AMPK activation regulates mTOR/SREBP-1c axis and Nrf2/ARE pathway to allay lipid accumulation and oxidative stress in steatotic HepG2 cells.

European Journal of Pharmacology
Ankita SharmaPoonam Kakkar

Abstract

Non-alcoholic fatty liver disease is emanating as a global cataclysm. This study was designed to investigate the antioxidative, anti-inflammatory and fat metabolism-regulating potential of berbamine (BBM), a natural bis-benzylisoquinoline alkaloid. BBM attenuated intracellular lipid accumulation in oleic-acid exposed HepG2 cells (0.5 mM) by inhibiting fatty acid uptake, lipogenesis, and promoting fatty acid β-oxidation by activating AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)-α. Berbamine (5 μM) induced AMPK activation (P < 0.001) via LKB1 (Ser-428) and elevated AMP:ATP ratio (P < 0.001). AMPK activation negatively regulated mTOR and also constrained the nuclear translocation of SREBP-1c and inhibited the lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) (P < 0.001). BBM stimulated nuclear translocation of redox-sensitive nuclear factor erythroid-2-related factor-2 (Nrf2) and increased hepatic expression of Nrf2 responsive enzymes, HO-1 and Nqo-1. BBM treatment reduced the oxidative burst and pro-inflammatory responses by significantly enhancing hepatic antioxidant defenses [SOD (P < 0.001), catalase (P < 0.001) and cellular glutathione (P < 0.01)] and dimi...Continue Reading

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Citations

Dec 31, 2020·International Journal of Molecular Sciences·Fiona M Russell, David Grahame Hardie
Feb 1, 2021·Chinese Journal of Natural Medicines·Ying-Rong LengHao Zhang
Jun 24, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Ziye ZhuYanqi Dang
Aug 6, 2021·Drug and Chemical Toxicology·Sherry SachdevaS J S Flora

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