Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells.
ABSTRACT Resveratrol (3,4',5-trihydroxy stilbene), a phytoalexin found in the skin and seeds of grapes, has been reported to possess anti-inflammatory, anticarcinogenic, and antioxidant activities. In this work, we assessed the ability of resveratrol to upregulate heme oxygenase-1 (HO-1) gene expression via activation of NF-E2-related factor 2 (Nrf2) in cultured PC12 cells. Nrf2 is a transcription factor involved in the cellular protection against oxidative stress through antioxidant response element (ARE)-directed induction of several phase 2 detoxifying and antioxidant enzymes, such as HO-1. Here, we report that resveratrol induces HO-1 expression via the ARE-mediated transcriptional activation of Nrf2. Moreover, PC12 cells treated with resveratrol exhibited transient activation of Akt/protein kinase B and extracellular signal-regulated protein kinase 1/2 (ERK1/2). LY294002 and U0126, pharmacological inhibitors of phosphatidylinositol 3-kinase and MEK1/2 which are upstream of Akt and ERK1/2, respectively, attenuated resveratrol-induced HO-1 expression and exhibited antioxidant effects. Taken together, the above findings suggest that resveratrol augments cellular antioxidant defense capacity through induction of HO-1 via Nrf2-ARE signaling, thereby protecting PC12 cells from oxidative stress.
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ABSTRACT: Dieckol was previously reported to exhibit antioxidant and anticancer activities in vitro studies. In this study, we characterised the mechanism underlying the dieckol-mediated expression of antioxidant and detoxifying enzymes. Dieckol suppressed the production of intracellular reactive oxygen species in the presence or absence of H2O2 and increased glutathione level in HepG2 cells. Dieckol enhanced the activities of antioxidant enzymes, and the expression of detoxifying enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO1), and glutathione S-transferase (GST) in HepG2 cells. Enhanced expression of antioxidant and detoxifying enzymes by dieckol was presumed to be the activation of the nuclear factor erythroid-derived 2-like 2 (Nrf2) demonstrated by its nuclear translocation and transcriptional activity via activation of mitogen-activated protein kinases in HepG2 cells. Furthermore, we demonstrated dieckol induced the expression of HO-1 in mouse liver. These results demonstrate that the dieckol-mediated cytoprotection in HepG2 cells is mediated through a ROS-independent up-regulation of antioxidant and detoxifying enzymes via Nrf2 activation as well as its intrinsic antioxidant activity, suggesting that dieckol may be used as a natural cytoprotective agent. Copyright © 2014 Elsevier Ltd. All rights reserved.Food Chemistry 05/2015; 174:538-46. · 3.26 Impact Factor
- Journal of clinical & experimental pathology. 05/2012; Suppl 4.
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ABSTRACT: Resveratrol is an effective anti-aging molecule with diverse biologic activity. It functions as a dual antioxidant that can neutralize free radicals and increase intrinsic antioxidant capacity. Additionally resveratrol increases mitochondrial biogenesis and has anti-inflammatory, anti-diabetic, and anti-cancer activity. In this paper we will focus on the use of topically applied resveratrol using a proprietary blend containing 1% resveratrol, 0.5% baicalin, and 1% vitamin E. This stabilized high concentration formulation demonstrates percutaneous absorption and alterations in gene expression such as hemoxygenase-1 (HO-1), vascular endothelial growth factor (VEGFA), and collagen 3 (COL3A1). Clinical assessment showed a statistically significant improvement in fine lines and wrinkles, skin firmness, skin elasticity, skin laxity, hyperpigmentation, radiance, and skin roughness over baseline in 12 weeks. Ultrasound measurements in the periorbital area showed an average improvement of 18.9% in dermal thickness suggesting significant dermal remodeling. These studies confirm that topical resveratrol, baicalin, and vitamin E are valuable ingredients that can be used for skin rejuvenationJournal of drugs in dermatology: JDD 12/2014; December 2014(Issue 12):Volume 13. · 1.32 Impact Factor