An in vivo study of hypoxia-inducible factor-1α signaling in ginsenoside Rg1-mediated brain repair after hypoxia/ischemia brain injury

Abstract

Hypoxia/ischemia (HI) brain injury is a common central nervous system insult in newborns. Studies have demonstrated bioactivity of ginsenoside Rg1 in increasing neural viability and promoting angiogenesis. However, there are few reports on roles of Rg1 in brain repair of neonatal HI, and the mechanisms involved are unclear. a neonatal HI model was established by a modified Rice-Vannucci model (RVM) and pups received ginsenoside Rg1 or monosialotetrahexosyl ganglioside (GM1) treatment. Neurological function and pathologic damage of rats were evaluated. Cellular apoptosis was detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Immunohistochemistry for von willebrand factor (vwf) was used to label micro vessels. Expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and cleaved caspase 3 (CC3) were detected by western blot. Both Rg1 and GM1 reduced neurological impairment and pathologic damage after HI by enhancing neural survival. Rg1, but not GM1, could also facilitate angiogenesis after HI. These pharmacological effects of Rg1 may be attributed to regulation of expression level of VEGF and CC3 and HIF-1α signaling pathway was involved. Rg1 plays a neuroprotective role in brain repair following neonatal HI, and HIF-1α is a potential target for therapeutic intervention in neonates with HI brain injury.