6-Hydroxy flavone rescue ethanol-induced apoptotic neurodegeneration via activation of p-Akt signaling pathway in the developing mice brain
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Abstract
Objective: To investigate the potential use of 6-Hydroxyflavone (6-HF) activation of phosphorylated Akt (p-Akt) to reduce neurodegeneration induced by Ethanol in the developing mice brain of post-natal day 7 (PND-7) mice.
Methods: This experimental study was conducted from March to June 2023 at Neuro Molecular Medicines Research Center, in collaboration with Shaheed Benazir Bhutto Women University, Peshawar-Pakistan. Twenty postnatal day-7 (PND-7) mice were randomly divided into four groups: control, EthOH, EthOH+6-HF, and 6-HF. Ethanol (5 mg/kg) was administered subcutaneously to the EthOH group. 6-HF was administered at a dose of 30 mg/kg to both the EthOH+6-HF and 6-HF groups. Four hours after administration, all mice were sacrificed for brain tissue collection and Western blot analysis. Densitometric quantification of protein bands was performed using ImageJ software. Statistical analysis was done using one-way ANOVA followed by post-hoc Tukey’s test, with p≤0.05 considered significant.
Results: Significant differences in p-Akt levels along with BAX, Bcl-2, Cas-3 and PARP-1 protiens were observed in the brain homogenates of PND 7 mice in various groups. Post hoc tukey test revealed significant increase (p<0.001) in the p-Akt, BAX, Bcl-2, Cas-3 and PARP-1 levels in EthOH group as compared to control group mice. However, significant increase (p<0.05) was observed in p-Akt level along with significant retrieval (p<0.001) in BAX, Bcl-2, Cas-3 and PARP-1 expression level in EthOH+6-HF group as compared to EthOH group.
Conclusion: Administration of 6-HF significantly improved ethanol induced neurodegeneration in brain of the PND-7 mice, potentially through modulation of the p-Akt signaling pathway.
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