# GuiLingJi ameliorates mild cognitive impairment by targeting unsaturated fatty acid metabolism to inhibit GPR120/NF-κB mediated neuroinflammation

## TL;DR

GuiLingJi, a traditional Chinese medicine, helps improve mild cognitive impairment by reducing brain inflammation through fatty acid metabolism.

## Contribution

The study reveals a novel mechanism by which GuiLingJi alleviates MCI via GPR120/NF-κB mediated neuroinflammation.

## Key findings

- GLJ reduces oxidative stress, inflammation, and hippocampal damage in MCI rat models.
- GLJ modulates unsaturated fatty acid metabolism, including linoleic and α-linolenic acid levels.
- GLJ inhibits the NF-κB/TNF-α pathway through GPR120 activation.

## Abstract

Mild cognitive impairment (MCI) is an intermediate condition between normal aging and dementia. Drug intervention is an important way to prevent MCI from developing into dementia. GuiLingJi (GLJ) is a traditional Chinese medicine formulae and it has the effect of enhancing memory. In view of the absence of special effective drugs for MCI, GLJ warrants investigation as a potential therapeutic agent.

This study uses a rat model of MCI, induced by D-galactose injections and a semi-high-fat diet, to explore the therapeutic efficacy of GLJ in MCI and elucidate the potential underlying pharmacological mechanisms by behavioral experiments and biochemical indexes, combined with serum and hippocampal metabolomics.

GLJ treatment mitigated D-galactose combined with semi-high-fat diet induced impairments, including abnormal blood lipids, oxidative stress, inflammation, cholinergic dysfunction, apoptosis, and reduced brain-derived neurotrophic factors, along with hippocampal damage. LC-MS metabolomics indicated that these effects involved unsaturated fatty acid and amino acid metabolism. By normalizing linoleic acid and α-linolenic acid levels and activating GPR120, GLJ inhibited the NF-κB/TNF-α pathway.

These findings demonstrate that GLJ alleviates MCI symptoms, at least in part, by modulating fatty acid metabolism and suppressing neuroinflammation via the GPR120/NF-κB pathway. This study supports GLJ as a promising proprietary TCM formulation for MCI treatment.