Effect Of Propolis On Vascular Endothelial Cells And Molecular Mechanisms

Propolis, a resinous material collected by honeybees (Apis mellifera L.) from leaf buds and cracks in the bark and mixed with pollen, wax and bee enzymes, possesses various physiological activities. It has been used in folk medicine since ancient times in many countries. Recently, it was reported to possess various biological activities, such as antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, anticancer, and antiangiogenesis activities. For this reason, propolis has been extensively used in food and beverages to improve health and prevent diseases such as inflammation, heart disease, diabetes and cancer.We previously reported that propolis exhibited significant antidiabetics antiatheroscloresis, anti-inflammatory effects in animal models. However, the molecular mechanisms underlying such protect effects of propolis have not been fully elucidated. The endothelium plays a crucial role in maintaining normal blood vessels fuctions. Endothelial activation, dysfunction or damage causes many diseases including diabetes, atherosclerosis, hypertension, septemia, and tumor. The regulation of endothelial cell apoptosis is a potential therapeutic target in blood vessel diseases. Thus, the studies concerning endothelial apoptosis signal pathway have raised many interests.The reports of Miao et al indicated that integrinβ4, phosphatidylcholine-specific phospholipase C (PC-PLC), p53 and reactive oxygen species (ROS) played important roles in the signal pathway affecting Human umbilical vein endothelial cells (HUVECs) apoptosis. As there were few reports concerning the effects and dose of propolis in treating HUVECs, in this study, we first investigated the effects of different concentrations of propolis in different HUVECs damage, which is induced by depriving of basic fibroblast growth factor (FGF-2), lipopolysaccharide (LPS) and oxidized low-density lipoprotein. We then further analyzed changes in integrinβ4, PC-PLC, p53 and ROS levels as well as mitochondrial membrane potential at different times. Furthermore, we studied the effects of propolis on the expression of Toll like receptor 4 (TLR4) in inflammatory condition. We aimed to elucidate the dose and molecular mechanisms of propolis in HUVECs damage, and provide experiment basis for the protect effects of propolis in diabetes, cardiovascular diseases and inflammation.Our reslults firstly showed that Brazilian propolis at high concentrations may be an apoptosis-inducing agent associated with the signal pathway mediated by integrinβ4, p53, ROS and mitochondrial membrane potential. Low concentrations of Brazilian propolis and Chinese propolis could decrease the level of integrin P4, PC-PLC, p53 and ROS in HUVECs. Howerver, at high concentrations, Chinese propolis may have some cell toxicology for decreasing mitochondrial membrane potential.Secondly, propolis depressed the expression of TLR4 and PC-PLC activity, further inhibiting the downstream signal molecular such as NF-κB p65, p53, ROS and NO level in HUVECs induced by LPS.Thirdly, propolis depressed PC-PLC activity and ROS level. However, propolis had no effect on p53 expression in HUVECs induced by ox-LDLIn conclusion, we studied the effects of propolis on vascular endothelial cells, and found that the effects of propolis on HUVECs apoptosis were dose dependent. At low concentrations, Brazilian propolis and Chinese propolis could protect HUVECs. However, Brazilian propolis and Chinese propolis at high concentration may be an apoptosis-inducing agent and have cytotoxicity.