Resveratrol Inhibits Inflammatory Responses via the Mammalian Target of Rapamycin Signaling Pathway in Cultured LPS-Stimulated Microglial Cells

Background: Resveratrol have been known to possess many pharmacological properties including antioxidant, cardioprotective and anticancer effects. We investigate the effect of anti-inflammatory and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells.

Methodology/Principal Findings: BV-2 cells were treated with resveratrol (25, 50, and 100 mM) and/or LPS (1 mg/ml). Nitricoxide (NO) and prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR and double immunofluorescence labeling, respectively. Resveratrol increased PTEN, Akt and mTOR phosphorylationin a dose-dependent manner or a time-dependent manner. Rapamycin (10 nM), a specific mTOR inhibitor, blocked theeffects of resveratrol on LPS-induced microglial activation.

 Conclusion and Implications: This study indicates that resveratrol inhibited LPS-induced proinflammatory enzymes andproinflammatory cytokines via down-regulation phosphorylation of NF-kB, CREB and MAPKs family in amTOR-dependentmanner. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of resveratrol.