Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the mechanism of AEPL on saturated long-chain fatty acid-induced lipotoxicity in HepG2 cells. Moreover, the phytochemical composition of AEPL was identified in the present study. HepG2 cells treated with palmitic acid (PA) were used for exploring the effect of AEPL on lipid accumulation, apoptosis, ER stress, and antioxidant response. The chemical composition of AEPL was analyzed by HPLC-ESI-MS/MS. AEPL treatment reduced PA-induced ROS production and lipid accumulation. Further molecular results revealed that AEPL restored cytochrome c in mitochondria and decreased caspase 3 activity to cease apoptosis. In addition, AEPL in PA-stressed HepG2 cells significantly reduced the ER stress and suppressed SREBP-1 activation for decreasing lipogenesis. For defending PA-induced oxidative stress, AEPL promoted Nrf2 expression and its target genes, SOD1 and GPX3, expressions. The present study suggested that AEPL protected from PA-induced lipotoxicity through reducing ER stress, increasing antioxidant ability, and inhibiting apoptosis. The efficacy of AEPL on lipotoxicity was probably concerned with kaempferol and isorhamnetin derived compounds.

Background: Protective effects ofGynura bicoloraqueous extract (GAE) at three concentrations upon nerve growth factor (NGF) differentiated-PC12 cells against H₂O₂induced injury were examined.Methods: NGF differentiated-PC12 cells were treated with GAE at 0.25%, 0.5% or 1%. 100 μM H₂O₂was used to treat cells with GAE pre-treatments. After incubating at 37 °C for 12 hr, experimental analyses were processed.Results: H₂O₂exposure decreased cell viability, increased plasma membrane damage, suppressed Bcl-2 mRNA expression and enhanced Bax mRNA expression. GAE pre-treatments reversed these changes. H₂O₂exposure reduced mitochondrial membrane potential, lowered Na⁺-K⁺-ATPase activity, and increased DNA fragmentation and Ca²⁺release. GAE pre-treatments attenuated these alterations. H₂O₂stimulated the production of reactive oxygen species (ROS), interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha, lowered glutathione content, and reduced glutathione peroxidase (GPX) and catalase activities. GAE pretreatments maintained GPX and catalase activities; and concentration-dependently diminished the generation of ROS and inflammatory cytokines. H₂O₂enhanced mRNA expression of nuclear factor kappa (NF-κ) B and p38. GAE pre-treatments decreased mRNA expression of NF-κB and p38. Conclusion: These findings suggested that GAE might be a potent neuronal protective agent.