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Naringenin Alleviates Acute Ethanol Exposure-induced Nerve Injury Through Regulating Neuroinflammation via PI3K/AKT Pathway-Mediated Modulation of Microglial M1/M2 Polarization

Year: 2026

Type: article

Abstract: Excessive alcohol consumption results in substantial neurotoxicity and contributes to the development of multiple neuropathological conditions.Regulation of neuroinflammatory processes is considered a critical determinant in mitigating alcohol-induced neuronal damage.Naringenin, the bioactive aglycone of naturally occurring citrus flavanone glycosides such as naringin, has been widely reported to possess potent antioxidant and anti-inflammatory activities.In the present study, we investigated whether naringenin exerts neuroprotective effects against acute ethanol-induced nerve injury.Naringenin treatment attenuated ethanol-induced intoxication, oxidative stress, apoptosis, and cellular stress, while maintaining neuronal morphology and functional integrity.Network pharmacology analysis further identified microglia as key cellular mediators underlying the anti-neuroinflammatory effects of naringenin.Mechanistically, naringenin markedly suppressed microglial activation and ethanol-induced morphological abnormalities in vivo, promoted a phenotypic shift toward the anti-inflammatory M2 subtype, and regulated the balance between pro-and anti-inflammatory cytokine production.Prophylactic intervention further indicated that these regulatory effects are mediated through activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.Additionally, co-culture experiments demonstrated that naringenin-induced suppression of pro-inflammatory cytokine release in microglia effectively preserved neuronal activity.These findings not only elucidate the regulatory role of naringenin in microglial polarization during acute ethanol exposure but also reveal its underlying neuroprotective mechanisms, thereby providing novel insights into the therapeutic potential of naringenin as a protective agent against acute ethanol-induced nerve injury.

Source: Food Science and Human Wellness

DOI: 10.26599/fshw.2026.9251116

Authors: Changming Yang, Hongxi Zheng, Han Wang, Yinjia He, Xiaodong Liu, Linqing Miao

Institutions: Beijing Institute of Technology, Peking University, State Key Laboratory of Membrane Biology, Beijing University of Chinese Medicine

Language: English

Topic: Neuroinflammation and Neurodegeneration Mechanisms

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W7160066758