# A Chloroform Fraction Derived from Vitis vinifera Root Ethanol Extract Attenuates Lipopolysaccharide-Induced Inflammatory Responses and Cognitive Dysfunction in BV-2 Microglia Cells and C57BL/6J Mouse Model

## TL;DR

A compound from grapevine roots reduces inflammation and cognitive issues in cells and mice, suggesting it could help treat neurodegenerative diseases.

## Contribution

The study identifies a chloroform fraction from Vitis vinifera root extract that inhibits neuroinflammation and cognitive dysfunction via NF-κB and TRIF pathways.

## Key findings

- The chloroform fraction suppressed LPS-induced proinflammatory cytokines in BV-2 microglia cells.
- CF reduced cognitive dysfunction and inflammatory responses in an LPS-induced mouse model.
- CF inhibited NF-κB activation and modulated TRIF signaling to suppress inflammation.

## Abstract

This study aimed to investigate the inhibitory effect of the chloroform fraction (CF) from Vitis vinifera root extract on LPS-induced neuroinflammation in BV-2 microglia cells and a C57/BL6J mouse model. CF significantly suppressed LPS-induced proinflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in BV-2 microglia cells. Mechanistically, CF inhibited LPS-induced activation of nuclear factor-κB (NF-κB) by blocking the p65 subunit and preventing the phosphorylation of NF-kappa-B inhibitor α (IκBα), while its effect was independent of the mitogen-activated protein kinase (MAPK) pathway. Furthermore, CF modulated the TRIF signaling pathway by regulating TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3), which contributed to the suppression of inflammatory mediators in BV-2 microglia cells. In vivo, we evaluated the neuroprotective effects of CF against cognitive dysfunction and inflammatory responses in an LPS-induced mouse model. Our behavioral assessments, including the Morris water maze and Y-maze tests, demonstrated that CF alleviated LPS-induced spatial learning impairment and cognitive decline. Additionally, CF significantly reduced the levels of inflammatory cytokines in serum and inflammatory mediators proteins expression in whole brain in LPS-injected mice, suggesting a direct link between reduced inflammatory responses and improved cognitive function. These findings suggest that CF from V. vinifera root extract may serve as a potential therapeutic strategy for neurodegenerative diseases mediated by microglial activation, such as Alzheimer’s disease.