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Metal-Associated Particulate Matter (PM2.5) Induces Cognitive Dysfunction: Polygonum multiflorum Improves
Hye Ji Choi1, Hyo Lim Lee1, Ho Jin Heo1
1Division of Applied Life Science (BK21), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea.
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.
Insights
Polygonum multiflorum extract (EPM) protects against fine particulate matter (PM2.5) induced cognitive decline by reducing oxidative stress and neuroinflammation. This study highlights EPM as a potential functional food for brain health.
Area of Science:
- Neuroscience
- Environmental Health
- Pharmacology
Background:
- Fine particulate matter (PM2.5) exposure is linked to cognitive dysfunction.
- PM2.5 induces neuroinflammation, oxidative stress, and mitochondrial dysfunction.
- Heavy metals in PM2.5 contribute to these detrimental effects.
Purpose of the Study:
- To evaluate the neuroprotective effects of Polygonum multiflorum extract (EPM) against PM2.5-induced cognitive impairment.
- To investigate the mechanisms underlying EPM's protective actions.
- To standardize EPM using HPLC for its bioactive compound, tetrahydroxystilbene glucoside (TSG).
Main Methods:
- A mouse model was used to assess PM2.5-induced cognitive deficits.
- Behavioral tests evaluated learning and memory.
- Biochemical assays measured oxidative stress markers (SOD, GSH, MDA, mtROS), mitochondrial function (membrane potential, ATP), and inflammatory pathways (TLR4-MyD88-NF-κB, JNK).
- Blood-brain barrier integrity and synaptic plasticity markers (BDNF/TrkB) were analyzed.
- Cholinergic system components (ACh, AChE, ChAT) were quantified.
- High-performance liquid chromatography (HPLC) identified tetrahydroxystilbene glucoside (TSG).
Main Results:
- EPM treatment significantly improved learning and memory in mice exposed to PM2.5.
- EPM restored redox homeostasis by increasing SOD and GSH and decreasing MDA and mtROS.
- Mitochondrial function, including membrane potential and ATP levels, was recovered.
- EPM inhibited neuroinflammation via the TLR4-MyD88-NF-κB pathway and maintained blood-brain barrier integrity.
- Neuronal apoptosis was modulated via the JNK pathway, reducing amyloid-beta and phosphorylated tau accumulation.
- Synaptic plasticity and cholinergic neurotransmission were preserved.
- HPLC confirmed TSG as a key component of EPM.
Conclusions:
- Polygonum multiflorum extract (EPM) demonstrates significant neuroprotective effects against PM2.5-induced cognitive dysfunction.
- EPM mitigates cognitive impairment by combating oxidative stress, neuroinflammation, mitochondrial dysfunction, and neuronal apoptosis.
- EPM holds promise as a functional food for preventing or treating cognitive deficits associated with PM2.5 exposure.
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