Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation

Abstract

Parkinson's disease (PD) is a movement disorder characterized by a progressive loss of nigrostriatal dopaminergic neurons. Microglia activation and neuroinflammation have been associated with the pathogenesis of PD. Indeed, cytokines have been proposed as candidates that mediate the apoptotic cell death of dopaminergic neurons seen in PD. In this study, we investigated the effect of two natural polyphenols, resveratrol and quercetin, on neuroinflammation. For glial cells, we observed that lipopolysaccharide (LPS)-induced mRNA levels of two proinflammatory genes, interleukin 1-alpha and tumor necrosis factor-alpha, are strongly decreased by treatments with resveratrol or quercetin. We also undertook microglial-neuronal coculture to examine the influence of resveratrol and quercetin on dopaminergic neuronal cell death evoked by LPS-activated microglia. Cytotoxicity assays were performed to evaluate the percentage of cell death, with apoptotic cells identified by both the TdT-mediated dUTP nick end labeling technique and the detection of cleaved caspase-3. We report that treatment of N9 microglial cells with resveratrol or quercetin successfully reduced the inflammation-mediated apoptotic death of neuronal cells in our coculture system. Altogether our results demonstrate that resveratrol and quercetin diminished apoptotic neuronal cell death induced by microglial activation and suggest that these two phytoestrogens may be potent antiinflammatory compounds.

Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and pro-inflammation gene expression in PC12 cells and in zebrafish

“…Hence, modulation of NO production, glial signalling cascades and pro-inflammatory cytokines might result in suppression of neuro-inflammation and may ultimately protect against neurodegeneration. Although the neuroprotective effects of quercetin are found to be via its anti-oxidative and antiinflammatory capacity in an in vitro system of lipopolysaccahride-activated co-culture of microglial and neuronal cells (7,8), it is uncertain whether its mode of action in the in vivo PD model involves anti-inflammation.…”

Antiproliferative and pro-apoptotic effects of quercetin on human pancreatic carcinoma cell lines EPP85-181P and EPP85-181RDB.

“…Moreover, Q amplifies action of the cytostatic drug on cells of the sensitive line, which provides perspective for decreasing dosage of the drug. This might be particularly valuable that the synergistic effects of Q and DB in their antiproliferative and pro-apoptotic actions take place only in cases of neoplastic cells, while normal cells in parallel are protected, also against toxic action of cytostatic drugs [3,16,51].…”

“…For the last decades Q has been known as a strong antioxidant, an anti-inflammatory agent, a vaso-dilatatory compound, and an agent which decreases blood pressure and inhibits aggregation of blood platelets [1][2][3]. Also on multiple occasions Q was found to exert antineoplastic effects on all stages of carcinogenesis [1,2,4,5].…”

Anti-Inflammatory Role of Natural Polyphenols and Their Degradation Products

“…Moreover, in glial cells it was shown that quercetin can inhibit LPS-induced mRNA levels of two cytokines, i.e. TNF-and IL-1 (Bureau et al, 2008). It has already been shown that quercetin can inhibit the production as well as the gene expression of TNF-via modulation of NF-κB in human peripheral blood mononuclear cells (Nair et al, 2006).…”