Protective effects of paeoniflorin against cobalt chloride-induced apoptosis of endothelial cells via HIF-1α pathway

Accumulating evidence has suggested the importance of hypoxia in the initiation and development of atherosclerotic lesion, and hypoxia has a profound impact on endothelial cell properties during cardiovascular disease processes. Paeoniflorin, isolated from the root of Paeonia lactiflora pall, can protect endothelial cells from hypoxic damage in a variety of ways, such as by enhancing the production of nitric oxide (NO) and decreasing the expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This study evaluated the protective effects of paeoniflorin against cobalt chloride (CoCl ₂, a hypoxia-mimicking agent)-induced apoptosis of endothelial cells (CRL-1730) and the underlying mechanisms in vitro. Endothelial cells were exposed to CoCl ₂ with or without pre-treatment with different concentrations of paeoniflorin. After treated with 0.6mM CoCl ₂ for 24h, endothelial cells showed significant decrease in cell viability and increased apoptosis rate, which could be reversed by pre-treatment with paeoniflorin. Similarly, pre-treatment with paeoniflorin could prevent CoCl ₂-induced hypoxia-induced factor-1α (HIF-1α) accumulation and down-regulate the expressions of p53 and Bcl-2/adenovirus E1B 19kDa interacting protein 3 (BNIP3). These findings indicate that paeoniflorin had effective protection against hypoxia-induced apoptosis of endothelial cells and that HIF-1α, p53 and BNIP3 might be involved in this process.