# Epicatechin Protects Against Post-Cardiac Arrest Brain Injury in Aged Rats via NRG1-Mediated Suppression of Neuroinflammation

## TL;DR

Epicatechin reduces brain injury after cardiac arrest in old rats by suppressing inflammation linked to aging.

## Contribution

Epicatechin's protective effect against post-cardiac arrest brain injury in aged rats via the NRG1-NF-κB pathway is newly demonstrated.

## Key findings

- Epicatechin reduced aging-related inflammation and brain injury in aged rats after CA/CPR.
- EC treatment decreased pro-inflammatory factors and NF-κB pathway proteins in aged rats.
- NRG1-ErbB4 expression was enhanced in EC-treated aged rats, suggesting pathway inhibition.

## Abstract

Chronic inflammation conducts an irreplaceable role in the aging process. More importantly, the impact is particularly significant in scenarios involving cardiac arrest and cardiopulmonary resuscitation (CA/CPR), where elderly individuals are inclined to suffer from more severe inflammatory injuries when compared to younger counterparts. Network pharmacology demonstrated a tight correlation between epicatechin (EC), aging, and the NRG1-NF-κB signaling pathway. With an aim to investigate whether EC suppressing inflammatory aging and alleviating post-CA/CPR brain injury is associated with the inhibition of the NRG1-NF-κB pathway, we established a model of naturally aged 21-month-old rats subjected to CA/CPR. A network pharmacology method was employed to pinpoint possible pathways that connect EC to neuroinflammation associated with aging. Sixty rats were randomly divided into three groups for feeding: a control group (pure water) and EC groups (EC was administered by gavage at doses of 1 mg/kg and 2 mg/kg respectively from the 12th month). Those groups underwent a CA/CPR procedure. At 24-h post-resuscitation, neurological scores, cortical pathology staining and assessments of neural injury were conducted. Expression levels of NRG1-NF-κB pathway-relevant inflammatory factors and proteins underwent systematic investigation by carrying out ELISA, RT-PCR, and Western blotting. In comparison with the 21-month-old groups treated with water, the 21-month-old groups treated with EC at 1 mg/kg and 2 mg/kg demonstrated decreased β-galactosidase staining, aging-correlated proteins and pro-inflammatory factors and NF-κB pathway-relevant proteins, as well as reinforced NRG1-ErbB4 expression. EC lessened inflammatory aging and mitigates post-CA/CPR brain injury in aged rats, associated with the inhibition of the NRG1-NF-κB pathway.