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.

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.

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