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bioRxiv · 10.1101/2024.07.07.602423

Dihydromyricetin alleviated the damage of hypoxia-induced mouse neurons by reducing ROS levels and inhibiting the expression of PAR and gammaH2AX

Du, X.·Guo, Y.·Yang, J.
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Abstract

ObjectiveTo investigate the effect of dihydromyricetin on hypoxia-induced neurons, to understand the effect of dihydromyricetin on hypoxic-ischemic encephalopathy (HIE). MethodsCortical neurons were isolated from C57BL/6j mice (24 hour-year old), cultured, and subjected to 4h hypoxia and 20h reoxygenation to mimic the neonatal hypoxic-ischemic encephalopathy. After dihydromyricetin (20mol/L) treatment of hypoxia-induced neurons for 2h, CCK-8 assay was used to analyze the neuronal viability, Hoechst33342/PI double staining assay was used to analyze the neuronal death, Western blotting was used to analyze the expression of Poly ADP-ribose (PAR) polymer protein and {gamma}H2AX, comet assay was used to detect DNA damage, immunofluorescence staining was used to observe the nuclear translocation of apoptosis inducing factor, and 2,7-dichlorodihydrofluorescein diacetate was used to detect the expression of reactive oxygen species (ROS). ResultsCompared with the control groups, hypoxia-treated neurons exhibited significantly lower activity, higher neuronal death rate and the high expressions of PAR and {gamma}H2AX, hypoxia could also induce AIF nuclear translocation, increase tail DNA content and tail length, increase the expression of ROS in neurons; after dihydromyricetin treatment, neuronal activity were significantly increased, neuronal death rate, ROS levels, and the expressions of PAR and {gamma}H2AX were also decreased, AIF nuclear translocation was inhibited, the tail DNA content and tail length were also decreased. ConclusionDihydromyricetin could alleviate the damage of hypoxia-induced neurons through decreasing the levels of ROS and inhibiting the expressions of PAR and {gamma}H2AX, suggesting that dihydromyricetin may have the protective effect on HIE.

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Du, X., Guo, Y., Yang, J.. 2024-07-10. Dihydromyricetin alleviated the damage of hypoxia-induced mouse neurons by reducing ROS levels and inhibiting the expression of PAR and gammaH2AX. https://doi.org/10.1101/2024.07.07.602423

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