Resveratrol Inhibits NLRP3 Inflammasome-Induced Pyroptosis and miR-155 Expression in Microglia Through Sirt1/AMPK Pathway

Resveratrol is a natural polyphenolic compound with a wide range of biological activities such as antioxidant, anti-carcinogenic, anti-obesity, anti-aging, anti-inflammatory, immunomodulatory properties. Accumulating evidence suggests that resveratrol has pharmacological benefits in life-threatening diseases, including cardiovascular disease, cancer, diabetes, and neurodegenerative diseases. Resveratrol is widely known for its anti-inflammatory properties; however, signaling mechanisms of anti-inflammatory action are still elusive. Studies have illustrated that resveratrol can control different regulatory pathways by altering the expression and consequently regulatory effects of microRNAs. Our study aims to clarify the regulatory mechanisms of resveratrol in its anti-inflammatory features in the N9 microglial cell line. Our results demonstrated that resveratrol inhibits LPS- and ATP-activated NLRP3 inflammasome and protects microglial cells upon oxidative stress, proinflammatory cytokine production, and pyroptotic cell death resulting from inflammasome activation. Additionally, resveratrol inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and activates AMPK/Sirt1 pathways. Furthermore, our results indicated that resveratrol downregulated inflammasome-induced miR-155 expression. Then, inhibition of AMPK and Sirt1 pathways has significantly reversed protective effect of resveratrol on miR-155 expression. To sum up, our results suggest that resveratrol suppresses the NLRP3 inflammasome and miR-155 expression through AMPK and Sirt1 pathways in microglia.