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          <dc:title>Puerarin attenuates binge ethanol-induced cortical neurotoxicity in association with AKT/mTOR signaling and autophagy-related responses</dc:title>
          <dc:creator>Fu Liu (1601110)</dc:creator>
          <dc:creator>Shuying Huang (5676650)</dc:creator>
          <dc:creator>Hongwen Xiao (22261312)</dc:creator>
          <dc:creator>Yuhong Zhou (2414881)</dc:creator>
          <dc:creator>Long Lin (1358919)</dc:creator>
          <dc:creator>Zaiqiang Liu (25103409)</dc:creator>
          <dc:creator>Jumei Lan (25103412)</dc:creator>
          <dc:creator>Xiaohong Chen (220164)</dc:creator>
          <dc:creator>Hua Tian (220297)</dc:creator>
          <dc:subject>Biochemistry</dc:subject>
          <dc:subject>Medicine</dc:subject>
          <dc:subject>Genetics</dc:subject>
          <dc:subject>Molecular Biology</dc:subject>
          <dc:subject>Neuroscience</dc:subject>
          <dc:subject>Physiology</dc:subject>
          <dc:subject>Pharmacology</dc:subject>
          <dc:subject>Biotechnology</dc:subject>
          <dc:subject>Biological Sciences not elsewhere classified</dc:subject>
          <dc:subject>Mental Health</dc:subject>
          <dc:subject>Plant Biology</dc:subject>
          <dc:subject>Puerarin</dc:subject>
          <dc:subject>binge ethanol exposure</dc:subject>
          <dc:subject>cortical neurotoxicity</dc:subject>
          <dc:subject>AKT/mTOR signaling</dc:subject>
          <dc:subject>autophagy-related responses</dc:subject>
          <dc:description>&lt;p&gt;Puerarin (Pue), a major isoflavone derived from &lt;i&gt;Pueraria lobata&lt;/i&gt;, has demonstrated neuroprotective potential in multiple neurological disorders; however, its effects on ethanol (EtOH)-induced cortical injury and the associated molecular responses remain incompletely understood. In the present study, network pharmacology was combined with &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt; experiments to investigate molecular responses associated with the effects of Pue on EtOH-induced neurotoxicity. Public databases were used to predict targets of Pue and alcohol-related brain injury, followed by protein–protein interaction analysis, Gene Ontology annotation, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A total of 101 overlapping targets were identified, among which TNF, AKT1, EGFR, TP53, and PPARG emerged as major hub targets, and PI3K-Akt signaling pathway was among the pathways that remained significantly enriched after FDR correction. In a 4-day binge EtOH rat model, Pue attenuated EtOH-associated increases in oxidative stress, neuronal degeneration, and apoptotic markers in cortical tissue. This was accompanied by attenuation of the EtOH-associated reductions in the p-AKT/AKT and p-mTOR/mTOR ratios, as well as an attenuation of EtOH-associated changes in LC3, ATG5, and Beclin-1 expression. In primary cortical neurons, Pue partially attenuated the EtOH-associated loss of neuronal viability and preserved neurite morphology. Bafilomycin A1 (BafA1)-based analysis of LC3-II and p62/SQSTM1 showed an overall BafA1-sensitive increase in LC3-II without a significant treatment-dependent difference in the BafA1 response. Collectively, these findings suggest that Pue attenuates binge EtOH-induced cortical neurotoxicity in association with changes in AKT/mTOR phosphorylation and autophagy-related responses.&lt;/p&gt;</dc:description>
          <dc:date>2026-09-24T10:40:05Z</dc:date>
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          <dc:identifier>10.6084/m9.figshare.33981330.v1</dc:identifier>
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          <dc:rights>CC BY 4.0</dc:rights>
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