Resveratrol Activates Antioxidant Protective Mechanisms in Cellular Models of Alzheimer’s Disease Inflammation

Abstract

Resveratrol is a natural phenolic compound with known benefits against neurodegeneration. We analyzed in vitro the protective mechanisms of resveratrol against the proinflammatory monomeric C-reactive protein (mCRP). mCRP increases the risk of AD after stroke and we previously demonstrated that intracerebral mCRP induces AD-like dementia in mice. Here, we used BV2 microglia treated with mCRP for 24 h in the presence or absence of resveratrol. Cells and conditioned media were collected for analysis. Lipopolysaccharide (LPS) has also been implicated in AD progression and so LPS was used as a resveratrol-sensitive reference agent. mCRP at the concentration of 50 µg/mL activated the nitric oxide pathway and the NLRP3 inflammasome pathway. Furthermore, mCRP induced cyclooxygenase-2 and the release of proinflammatory cytokines. Resveratrol effectively inhibited these changes and increased the expression of the antioxidant enzyme genes Cat and Sod2. As central mechanisms of defense, resveratrol activated the hub genes Sirt1 and Nfe2l2 and inhibited the nuclear translocation of the signal transducer NF-ĸB. Proinflammatory changes induced by mCRP in primary mixed glial cultures were also protected by resveratrol. This work provides a mechanistic insight into the protective benefits of resveratrol in preventing the risk of AD induced by proinflammatory agents.

Levosimendan and Dobutamin Attenuate LPS-Induced Inflammation in Microglia by Inhibiting the NF-κB Pathway and NLRP3 Inflammasome Activation via Nrf2/HO-1 Signalling

“…Moreover, dobutamine effectiveness was also demonstrated in ischemic conditions both "in vitro" and "in vivo" through the stimulation of antioxidant genes [46,47]. Oxidative stress may be induced by pathogen-associated molecular patterns (PAMPs), such as LPS, that may activate different molecular pathways, including the NF-κB/NLRP3 pathway, thus playing a role in the pathogenesis of different diseases and also in neuroinflammation, well miming the consequences of hypovolemic shock in the CNS [48][49][50][51].…”

Resveratrol: A Review on the Biological Activity and Applications

“…Moreover, the antioxidant effect of RSV is very effective in neuronal differentiation due to the activation of SIRT1. Because of the anti-inflammatory action, it inhibits M1 microglia activation, which plays a part in the induction of neurodegeneration and stimulates Th2 responses by enhancing anti-inflammatory cytokines and SIRT1 [136,137].…”

Resveratrol: A Review on the Biological Activity and Applications

“…Moreover, the antioxidant effect of RSV is very effective in neuronal differentiation, due to the activation of SIRT1. Because of the anti-inflammatory action, it inhibits M1 microglia activation, which plays a part in the induction of neurodegeneration and stimulates Th2 responses by enhancing anti-inflammatory cytokines and SIRT1 [130,131].…”