Neuroprotection of Neuro2a cells and the cytokine suppressive and anti-inflammatory mode of action of resveratrol in activated RAW264.7 macrophages and C8–B4 microglia

Abstract

Chronic inflammation is a hallmark of neurodegenerative disease and cytotoxic levels of nitric oxide (NO) and pro-inflammatory cytokines can initiate neuronal death pathways. A range of cellular assays were used to assess the anti-inflammatory and neuroprotective action of resveratrol using murine microglial (C8-B4), macrophage (RAW264.7) and neuronal-like (Neuro2a) cell lines. We examined the release of NO by Griess assay and used a Bioplex array to measure a panel of pro- and anti-inflammatory cytokines and chemokines, in response to the inflammatory stimuli lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Resveratrol was a potent inhibitor of NO and cytokine release in activated macrophages and microglia. The activity of resveratrol increased marginally in potency with longer pre-incubation times in cell culture that was not due to cytotoxicity. Using an NO donor we show that resveratrol can protect Neuro2a cells from cytotoxic concentrations of NO. The protective effect of resveratrol from pro-inflammatory signalling in RAW264.7 cells was confirmed in co-culture experiments leading to increased survival of Neuro2a cells. Together our data are indicative of the potential neuroprotective effect of resveratrol during nitrosative stress and neuroinflammation.

Resveratrol-decreased hyperalgesia mediated by the P2X7 receptor in gp120-treated rats

“…RES has anti-inflammatory effects. 13–15 Our results suggested that RES relieved the HIV-associated pain behavior in the gp120 rats by influencing the P2X 7 receptor in the DRG SGCs.…”

“…13,14 RES exhibits anti-inflammatory and anti-nociceptive effects. 13–15 Adenosine triphosphate (ATP) is a signaling molecule in neuropathic and inflammatory pain. 16–18 Extracellular ATP can activate the ionotrophic P2X receptors in primary afferent fibers.…”

How efficient is resveratrol as an antioxidant of the Mediterranean diet, towards alterations during the aging process?

“…However, RSV did not change the expression of cyclooxygenase-2 (COX-2) but reduces the expression of cyclooxygenase-1 (COX-1) [68]. In addition to reducing the expression of cytokines, RSV suppresses also the NF-jB-stimulated production of NO [69][70][71]. Furthermore, it has been reported that RSV abrogates activator protein 1 (AP-1) dimer (c-Jun/FOS) activation through the inhibitory effect on extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) pathways [66].…”

Medicinal Plants of the Australian Aboriginal Dharawal People Exhibiting Anti-Inflammatory Activity

“…Therefore, pharmacological compounds with the ability to attenuate the production of these inflammatory molecules may have potential for the treatment of many inflammatory diseases including AD [21, 22, 28, 34, 35]. …”

“…In recent years, the search for novel anti-inflammatory drugs from a wide range of medicinal plant resources has been intensified, and a variety of plant secondary metabolites including apigenin, curcumin, cinnamaldehyde, and resveratrol have already been found to suppress inflammatory responses [21, 22, 28]. …”