Anti-inflammatory mechanism of α-viniferin regulates lipopolysaccharide-induced release of proinflammatory mediators in BV2 microglial cells

alpha-Viniferin is an oligostilbene of trimeric resveratrol and has anticancer activity; however, the molecular mechanism underlying the anti-inflammatory effects of alpha-viniferin has not been completely elucidated thus far. Therefore, we determined the mechanism by which alpha-viniferin regulates lipopolysaccharide (LPS)-induced expression of proinflammatory mediators in BV2 microglial cells. Treatment with alpha-viniferin isolated from Clematis mandshurica decreased LPS-induced production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)). alpha-Viniferin also downregulated the LPS-induced expression of proinflammatory genes such as iNOS and COX-2 by suppressing the activity of nuclear factor kappa B (NF-kappa B) via dephosphorylation of Akt/PI3K. Treatment with a specific NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC), indirectly showed that NF-kappa B is a crucial transcription factor for expression of these genes in the early stage of inflammation. Additionally, our results indicated that alpha-viniferin suppresses NO and PGE(2) production in the late stage of inflammation through induction of heme oxygenase-1 (HO-1) regulated by nuclear factor erythroid 2-related factor (Nrf2). Taken together, our data indicate that alpha-viniferin suppresses the expression of proinflammatory genes iNOS and COX-2 in the early stage of inflammation by inhibiting the Akt/PI3K-dependent NF-kappa B activation and inhibits the production of proinflammatory mediators NO and PGE(2) in the late stage by stimulating Nrf2-mediated HO-1 signaling pathway in LPS-stimulated BV2 microglial cells. These results suggest that alpha-viniferin may be a potential candidate to regulate LPS-induced inflammation. (C) 2014 Elsevier Inc. All rights reserved.