Neuroprotective effects of oxymatrine on hypoxic-ischemic brain damage in neonatal rats by activating the Wnt/β-catenin pathway

Neuronal apoptosis is a major pathological process associated with neurological dysfunction in neonates after hypoxic-ischemic brain damage (HIBD). Our previous study demonstrated that oxymatrine (OMT) exerts po-tential neuroprotective effects on neonatal rats subjected to hypoxic-ischemic insult. However, the underlying molecular mechanism remains unclear. In this study, we investigated the effects of OMT-mediated neuro-protection on neonatal HIBD by attempting to determine its effect on the Wnt/beta-catenin signaling pathway and explored the underlying mechanism. Both 7-day-old rat pups and primary hippocampus neurons were used to establish the HIBD and oxygen-glucose deprivation (OGD) injury models, respectively. Our results demonstrated that OMT treatment significantly increased cerebral blood flow and reduced S100B concentration, infarct vol-ume, and neuronal apoptosis in neonatal rats. In vitro, OMT markedly increased cell viability and MMP level and decreased DNA damage. Moreover, OMT improved the mRNA and protein levels of Wnt1 and beta-catenin, inhibited the expression of DKK1 and GSK-3 beta, enhanced the nuclear transfer of beta-catenin, and promoted the binding ac-tivity of beta-catenin with Tcf-4; however, it downregulated the expression of cleaved caspase-3 and cleaved caspase-9. Notably, the introduction of XAV-939 (a Wnt/beta-catenin signaling inhibitor) reversed the positive effects of OMT both in vivo and in vitro. Collectively, our findings demonstrated that OMT exerted a neuro-protective effect on neonatal HIBD by inhibiting neuronal apoptosis, which was partly via the activation of the Wnt/beta-catenin signaling pathway.

Automated summary

Oxymatrine exhibits neuroprotective effects on neonatal hypoxic-ischemic brain damage by inhibiting neuronal apoptosis through the activation of the Wnt/beta-catenin signaling pathway.