Work

Neuroprotective efficacy of methanolic extract of propolis against early life stress-induced oxidative and inflammatory damage: Involvement of the Nrf2–Keap1 signaling pathway

Year: 2025

Type: article

Abstract: Background Early-life stress (ELS) is a major environmental risk factor for neurobehavioral impairments, including cognitive dysfunction, repetitive behaviors, and social deficits. Propolis, a natural bee product with strong antioxidant and anti-inflammatory properties, may counteract oxidative stress–related disorders. This study examined whether methanolic extract of propolis (MEP) mitigates ELS-induced oxidative and inflammatory damage in a maternal separation (MS) rat model, focusing on the Nrf2–Keap1 pathway. Methods Male Wistar rats (200–220 g) were allocated to Control, Vehicle, Propolis (200 mg/kg), MS, and MS + Propolis (100 or 200 mg/kg) groups. ELS was induced by separating pups from dams for 3 h/day during postnatal days (P) 1–9. MEP was given orally from P21 to P42. Behavioral tests assessed social interaction, cognition, repetitive, and anxiety-like behaviors. Biochemical analyses measured antioxidant enzymes (SOD, CAT, GRx), glutathione, lipid peroxidation (MDA), and expression of Nrf2, Keap1, IL-6, and TNF-α. Results MEP (100 and 200 mg/kg) improved social interaction ( p < 0.05, p < 0.01), reduced repetitive behaviors ( p < 0.001), and enhanced cognition ( p < 0.05, p < 0.01) and anxiety-like behaviors ( p < 0.001) in MS rats. Treatment increased SOD, CAT, and GRx activities ( p < 0.01), elevated glutathione ( p < 0.001), upregulated Nrf2 ( p < 0.001), and reduced MDA ( p < 0.001), IL-6, and TNF-α, with stronger effects at 200 mg/kg ( p < 0.001). Conclusion MEP alleviates oxidative and inflammatory responses induced by ELS, likely via Nrf2–Keap1 modulation, supporting its potential as a complementary therapy for stress-related neurobehavioral disorders.

Source: IBRO Neuroscience Reports

DOI: 10.1016/j.ibneur.2025.10.010

Authors: Ilia Ahmadi Kholardi, Akbar Hajizadeh Moghaddam, Mohammadreza Bigdeli, Sedigheh Khanjani Jelodar

Institutions: Shahid Beheshti University, University of Mazandaran

Language: English

Topic: Bee Products Chemical Analysis

Subfield: Insect Science

Field: Agricultural and Biological Sciences

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,400