SIRT1 and major depressive disorder: In another study, the administration of apple phenolic extracts against lead acetate (Pb(Ac)2)-induced cognitive impairment and depression/anxiety-like behavior in mice revealed that the increased cellular oxidative damage and the levels of proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α were attenuated after the administration of apple phenolic extracts via the regulation of oxidative stress, neuroinflammation, and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway [73].