Abstract
Excess accumulation of lipids and oxidative stress in the liver contribute to nonalcoholic fatty liver disease (NAFLD). We hypothesized that Pinus densiflora Sieb. et Zucc. (PSZ) can protect against NAFLD by regulating lipid accumulation and oxidative stress in the liver. To investigate the effect of PSZ upon NAFLD, we used an established cellular model: HepG2 cells treated with oleic acid. Then, the extent of hepatic steatosis and oxidative stress was assessed and levels of inflammatory markers measured. Oleic acid-treated HepG2 cells, compared with controls, had greater lipid accumulation. PSZ decreased lipid accumulation by 63% in oleic acid-treated HepG2 cells. Additionally, PSZ decreased the target gene expression of lipogenesis such as sterol regulatory element binding protein-1c, fatty acid synthase, stearoyl-CoA desaturase-1, diacylglycerol O-acyltransferase-1, and acetyl-CoA carboxylase-1 by 1.75, 6.0, 2.32, 1.93 and 1.81 fold, respectively. In addition, Oleic acid-treated HepG2 cells elicited extensive accumulation of tumor necrosis factor-α (TNFα) by 4.53 fold, whereas PSZ-treated cells decreased the expression of TNFα mRNA by 1.76 fold. PSZ significantly inhibited oxidative stress induced by reactive oxygen species. These results suggest that PSZ has effects on steatosis in vitro and further studies are needed in vivo to verify the current observations.
Highlights
The liver is the main organ for coordinating regulation of energy metabolism and lipid trafficking.Excess intake of lipids in the diet can lead to fatty liver, which can progress to nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)
HepG2 cells were treated with Pinus densiflora Sieb. et Zucc. (PSZ) (100 μg/mL) and oleic acid (OA) (2 mM) for 24 h
PSZ suppressed the proliferation of HepG2 cells in a dose-dependent manner (Figure 1A)
Summary
The liver is the main organ for coordinating regulation of energy metabolism and lipid trafficking. The “second hit” is the progression of steatosis to NASH This progression is associated with oxidative stress and the release of cytokines that can induce inflammation, fibrosis, or necrosis [7]. Agents that can prevent or attenuate free fatty acid-induced lipogenesis and oxidative stress-induced damage represent promising therapeutic choices for NAFLD. Quercetin effectively reversed NAFLD symptoms by decreased triacylglycerol accumulation, insulin resistance, inflammatory cytokine secretion and increased cellular antioxidants in OA induced hepatic steatosis in HepG2 cells [24]. Due to the synergistic effect of known components such as ρ-coumaric acid, choline and quercetin, PSZ would be useful material for the anti-NAFLD. We investigated the beneficial effects of PSZ (a candidate for the treatment of NAFLD) on the inhibition of fat accumulation and oxidative stress in the liver
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