# Arctiin targets oxidative stress and inflammation, restores Neuregulin-1, and improves neurobehavioral outcomes in neonatal hypoxic-ischemic brain injury

## TL;DR

Arctiin, a natural compound, protects neonatal rats from brain injury by reducing inflammation and oxidative stress while improving brain function.

## Contribution

This study demonstrates that Arctiin restores Neuregulin-1 and improves neurobehavioral outcomes in neonatal hypoxic-ischemic brain injury.

## Key findings

- Arctiin reduces inflammation and oxidative stress markers like CRP and TOC.
- Arctiin increases antioxidant capacity and BDNF levels while restoring NRG-1 gene expression.
- Arctiin treatment improves sensorimotor function and reduces brain infarct volume in neonatal rats.

## Abstract

Hypoxic-ischemic brain damage (HIBD) represents a major cause of neonatal morbidity and mortality, resulting from perinatal oxygen deprivation and impaired cerebral blood flow. This study aims to investigate the neuroprotective effects of Arctiin, a bioactive lignan derived from Arctium lappa, recognized for its potent antioxidant and anti-inflammatory properties, in a neonatal rat model of HIBD.

Neonatal rats at postnatal day 8 were randomly assigned to four groups: Sham-operated (SHAM), Hypoxia-Ischemia (HI), Hypoxia-Ischmia with Solvent control (HI/SO), and Hypoxia-Ischemia treated with Arctiin (HI/Arc). HIBD was induced via unilateral carotid artery ligation followed by exposure to hypoxia. The HI/Arc group was administered Arctiin orally at a dosage of 60 mg/kg daily for seven consecutive days. Behavioral performance, biochemical parameters, histological integrity, and gene expression profiles were assessed to evaluate the neuroprotective efficacy of Arctiin.

Arctiin administration resulted in a significant reduction in C-reactive protein (CRP), and total oxidant capacity (TOC). Simultaneously, it enhanced total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF) levels. Histological analysis showed diminished infarct volume in the Arctiin-treated group. Moreover, gene expression studies revealed significant restoration of Neuregulin-1 (NRG-1) in group treated by arctiin. Neurobehavioral assessments further confirmed significant improvements in sensorimotor function in the Arctiin-treated group.

Our study provides evidence indicating that Arctiin mitigates hypoxic-ischemic brain damage in rat pups through a synergistic mechanism involving the suppression of inflammation and oxidative stress, coupled with the upregulation of critical neuroprotective genes and proteins, specifically NRG-1 gene expression and BDNF protein levels. Future studies should investigate the precise molecular pathways downstream of NRG-1 that mediate Arctiin's neuroprotective effects.

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•Arctiin shows neuroprotection in a neonatal rat model of hypoxic-ischemic brain injury.•It reduces key markers of inflammation and oxidative stress post-injury.•Treatment boosts antioxidant capacity levels.•Arctiin diminishes brain infarct volume and restores neuroprotective Neuregulin-1.•It leads to significant improvement in neurobehavioral and sensorimotor outcomes.

Arctiin shows neuroprotection in a neonatal rat model of hypoxic-ischemic brain injury.

It reduces key markers of inflammation and oxidative stress post-injury.

Treatment boosts antioxidant capacity levels.

Arctiin diminishes brain infarct volume and restores neuroprotective Neuregulin-1.

It leads to significant improvement in neurobehavioral and sensorimotor outcomes.