Resveratrol(via Hugo Francisco de Souza)

Studies have shown that resveratrol may fight Alzheimer's disease by suppressing inflammation 

In a recent study published in the journal Antioxidants, researchers investigated the mechanism by which resveratrol, a natural phenolic compound, prevents and mitigates Alzheimer's disease (AD). They used a BV2 microglial cell line established from a C57BL/g transgenic mouse model to elucidate the mechanistic benefits of the activation of glial cells by resveratrol's anti-proinflammatory monomer C-reactive protein (mCRP). Their findings highlight that resveratrol inhibits lipopolysaccharide (LPS) and McRp-induced cyclooxygenase-2, thereby blocking the release of pro-inflammatory cytokines. It further upregulates the expression of antioxidant enzymes, namely Cat and Sod2. Together, these results provide a mechanistic basis for the benefits of resveratrol in combating and controlling AD. 

About the study

In the present study, researchers attempt to evaluate the antioxidant protection mechanism of Resveratrol using BV2 microglia, which have been activated by monomeric C-reactive protein (mCRP). mCRP activation and overexpression are vital traits of most inflammation-activated diseases, and its prevention may delay or even reverse conditions like AD that progress in part due to inflammatory stress. 

The BV2 cell line used herein was established from C57BL/6 transgenic mice microglia, an established model for studying brain inflammation. mCRP was generated from pure CRP protein via urea/ ethylenediaminetetraacetic acid (EDTA) chelation, followed by dialysis. Escherichia coli 026:B26 was used as a lipopolysaccharide (LPS) strain. Resveratrol treatments on these primary cell cultures varied between 10-50 µM. mCRP assays utilized mCRP at 50 µg/mL. To avoid astrocyte damage, primary glial cultures were not subjected to nutrient (serum) starvation.

Nitric oxide generation by glial cultures was determined using the colorimetric Griess reaction. The Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect and measure tumor necrosis factor-alpha (TNF-α) and interleukin one-beta (IL1 ß) expressed in ng/mL and pg/mL, respectively. Western blotting assays were used to detect and identify other protein products produced by BV2 cells. BV2 cell RNA was then extracted and subjected to Real-Time Quantitative Polymerase Chain Reaction (qPCR) to determine relative gene expression.

Finally, the immunofluorescence assay was used to measure the impact of Resveratrol on BV2 cell expression. Statistical analyses comprised two-way analysis of variance (ANOVA) and the Shapiro–Wilk test.

Study findings

Resveratrol was observed to significantly inhibit and reduce TNF-α production induced by mCRP and LPS, elucidating and validating its anti-inflammatory properties. The compound was further observed to suppress the activation of the nitric oxide pathway, preventing the generation of reactive oxygen species (ROS).

Activation of the NLR family pyrin domain containing 3 (NLRP3) gene was also observed to be inhibited by Resveratrol. NLRP3 is the gene responsible for producing the cryopyrin protein, a crucial microglia cell sensor inflammasome activated during oxidative stress. Nuclear factor-κB (NF-κB) and Nos2 were observed to be downregulated on the addition of Resveratrol. Finally, Resveratrol was found to induce the expression of antioxidant genes, including Sirt1 and Nfe2I2.