Resveratrol attenuates LPS-induced oxidative stress and apoptosis in HMC3 microglial cells, partly involving NRF2-related signaling.

Abstract

Postoperative cognitive dysfunction (POCD) is associated with neuroinflammation and oxidative stress, but the underlying mechanisms remain unclear. Resveratrol (RES), a natural polyphenol, has shown neuroprotective potential; however, its effects on microglial injury related to postoperative neuroinflammation have not been fully characterized. In this study, potential shared targets of RES and POCD were first explored using network pharmacology, followed by experimental validation using an LPS-stimulated HMC3 microglial cell model. HMC3 cells were treated with LPS (1000 ng/mL) and RES (50 µM), either with or without the NRF2 inhibitor ML385 (1 µM). Cell viability, proliferation, apoptosis, ROS production, and NRF2-related markers were assessed using CCK-8, EdU staining, flow cytometry, qPCR, Western blotting, and immunofluorescence. Network pharmacology suggested that apoptosis- and NRF2-related antioxidant pathways may be involved in the effects of RES. LPS reduced cell viability and proliferation and increased apoptosis, ROS production, BAX expression, and Caspase-3-related expression. RES partially reversed these changes, increased NRF2, HO-1, and SOD2 expression, and decreased KEAP1 expression under LPS-stimulated conditions. These RES-associated effects were partly weakened by ML385. Overall, RES may attenuate LPS-induced oxidative stress and apoptosis in HMC3 microglial cells, partly involving NRF2-related signaling. This study provides in vitro evidence supporting the potential protective role of RES in microglial injury related to postoperative neuroinflammation.