# Metal-Associated Particulate Matter (PM2.5) Induces Cognitive Dysfunction: Polygonum multiflorum Improves Neuroinflammation and Synaptic Function

## TL;DR

This study shows that Polygonum multiflorum extract can reduce cognitive dysfunction caused by metal-rich PM2.5 pollution in mice by reducing inflammation and improving brain function.

## Contribution

The novel contribution is demonstrating the neuroprotective effects of Polygonum multiflorum extract against PM2.5-induced cognitive impairments through multiple molecular mechanisms.

## Key findings

- EPM treatment improved learning and memory in a mouse model of PM2.5-induced cognitive dysfunction.
- EPM reduced oxidative stress and restored mitochondrial function by increasing SOD, GSH, and decreasing MDA and mtROS.
- EPM inhibited neuroinflammation and preserved synaptic plasticity via TLR4-NF-κB and BDNF/TrkB pathways.

## Abstract

Fine particulate matter (PM2.5), which contains heavy metals such as Al, Fe, Mg, and Mn, among others, induces cognitive dysfunction through oxidative stress, neuroinflammation, and impaired mitochondria. This study evaluated the neuroprotective effects of a 40% ethanol extract of Polygonum multiflorum (EPM) on PM2.5-induced cognitive dysfunction in a mouse model. Behavioral assessments demonstrated attenuated learning and memory impairment following EPM treatment. Redox homeostasis was restored through increased expression of superoxide dismutase (SOD) and glutathione (GSH) and decreased levels of malondialdehyde (MDA) and mitochondrial reactive oxygen species (mtROS) in the EPM group. Mitochondrial function was attenuated, as indicated by recovery of mitochondrial membrane potential and ATP levels. EPM inhibited neuroinflammation by downregulating the TLR4-MyD88-NF-κB pathway and maintaining blood–brain barrier integrity through the upregulation of tight junction proteins. It modulated neuronal apoptosis through the JNK pathway, reducing the accumulation of amyloid-beta and phosphorylated tau. Synaptic plasticity was preserved through upregulation of BDNF/TrkB signaling and cholinergic neurotransmission via regulation of acetylcholine (ACh), acetylcholinesterase (AChE), and choline acetyltransferase (ChAT). To standardize EPM, high-performance liquid chromatography (HPLC) confirmed the presence of the bioactive compound, tetrahydroxystilbene glucoside (TSG). These findings suggest that EPM may be a promising functional food candidate for mitigating PM2.5-related cognitive impairments.