Protective effects of bellidifolin in hypoxia-induced in pheochromocytoma cells (PC12) and underlying mechanisms

Bellidifolin, a xanthone compound derived from Plants of Gentiana species, is known to exert a variety of pharmacological activities including anti-oxidation, anti-inflammatory and antitumor actions as well as a protective effect on cerebral ischemic nerve injury. The aim of this study was to examine the protective effects of bellidifolin on nerve injury produced by hypoxia and possible underlying mechanisms using pheochromocytoma cells (PC12). Data showed that the viability of PC12 cells subjected to hypoxia resulted in a significant decrease; however; pretreatment with certain concentrations of bellidifolin (20 or 40 μmol/L) prior to hypoxia significantly increased the survival rate. The results of immunohistochemical staining analysis revealed that there were no marked alterations in the expression of PERK protein between all bellidifolin groups while the expression of p-p38MAPK protein was significantly enhanced by hypoxia. Pretreatment with different concentrations of bellidifolin followed by hypoxia significantly decreased the expression of p-p38MAPK protein. The results of western blot analysis showed that hypoxia induced the expression of the MAPK signaling pathway downstream of the key Apoptosis factor Caspase-3. Compared to hypoxia, the expression of Caspase-3 in the presence of belliidifolin was significantly lower. Data suggest that bellidifolin may contribute to the protective effects associated with nerve injury initiated by hypoxia by mechanisms related to inhibition of cell Apoptosis independent of the ERK pathway, but may involve blockade of p38MAPK signaling pathway activation and downstream Caspase-3 expression.