Geniposide protects PC-12 cells against oxygen and glucose deprivation-induced injury by up-regulation of long-noncoding RNA H19

Aims: Hypoxic-ischemic encephalopathy (HIE) is a common brain injury disease in neonates, which can lead to neonatal disability and death. Geniposide (GEN) is a main ingredient of Gardenia jasminoides, whose anti-tumor, anti-inflammatory and anti-apoptotic effects have been reported in various diseases. However, the effect of GEN on HIE remains uninvestigated. This study aimed to clarify the protective effect of GEN on PC-12 cells against oxygen and glucose deprivation (OGD)-induced injury. Main methods: PC-12 cells were subjected to OGD treatment, cell viability, cell cycle-associated factors, apoptosis and apoptosis-associated factors were then determined. The different concentrations of GEN were used to stimulate PC-12 cells, and the effects of GEN on cell proliferation and apoptosis in OGD-treatment cells were assessed. Subsequently, relative expression level of H19 was analyzed in PC-12 cells after treatment with GEN. After this, si-H19 was transfected into PC-12 cells to explore the regulatory effect of H19 on PC-12 cells after treatment with GEN and OGD. Besides, PI3K/AKT and Wnt/β-catenin pathways were examined by western blot assay. Key findings: OGD significantly inhibited cell viability, decreased CyclinD1, CDK4 and CDK6 expression, induced apoptosis and up-regulated Cleaved-Caspase-9/-7/-3 expression in PC-12 cells. GEN treatment obviously alleviated OGD-induced cell injury. Additionally, H19 expression was up-regulated by GEN, and H19 knockdown reversed the protective effect of GEN on PC-12 cells against OGD-induced injury. Finally, GEN activated PI3K/AKT and Wnt/β-catenin pathways by regulating H19 in OGD-insulted PC-12 cells. Significance: The findings suggested that GEN protected PC-12 cells against OGD-induced injury by up-regulation of H19.