Alcohol-induced liver disease progresses due to increased reactive oxygen species (ROS) and cellular lipid peroxidation. Quercetin is a flavonoid with strong antioxidant and hepatoprotective effects. We investigated whether 3'--methyl quercetin (3'MQ) and quercetin-3--glucuronide (Q3GA), two metabolites of quercetin, have protective effects against ethanol-induced hepatotoxicity. Cell viability was increased by quercetin, 3'MQ, and Q3GA in HepG2 hepatocarcinoma cells exposed to ethanol. Our results show that this effect was mediated by diminished ROS generation, decreased lipid peroxidation and up-regulation of antioxidant capacity, including glutathione, superoxide dismutase and catalase. Moreover, down-regulated heme oxygenase-1 (HO-1) expression by ethanol was restored by quercetin, 3'MQ, and Q3GA through the activation of nuclear factor E2-related factor 2 and activator protein-1, but not nuclear factor-kappa B. Overall results suggest that 3'MQ, Q3GA, and quercetin attenuate oxidative stress in hepatocytes exposed to ethanol by up-regulating HO-1 expression and can be used as therapeutic agents for ameliorating alcohol-induced liver disease.

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Graphene is a noncytotoxic monolayer platform with unique physical, chemical, and biological properties. It has been demonstrated that graphene substrate may provide a promising biocompatible scaffold for stem cell therapy. Because chemical vapor deposited graphene has a two dimensional polycrystalline structure, it is important to control the individual domain size to obtain desirable properties for nano-material. However, the biological effects mediated by differences in domain size of graphene have not yet been reported. On the basis of the control of graphene domain achieved by one-step growth (1step-G, small domain) and two-step growth (2step-G, large domain) process, we found that the neuronal differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) highly depended on the graphene domain size. The defects at the domain boundaries in 1step-G graphene was higher (38.5) and had a relatively low (13% lower) contact angle of water droplet than 2step-G graphene, leading to enhanced cellsubstrate adhesion and upregulated neuronal differentiation of hMSCs. We confirmed that the strong interactions between cells and defects at the domain boundaries in 1step-G graphene can be obtained due to their relatively high surface energy, which is stronger than interactions between cells and graphene surfaces. Our results may provide valuable information on the development of graphene-based scaffold by understanding which properties of graphene domain influence cell adhesion efficacy and stem cell differentiation.