Malaysian tualang honey inhibits pdgfinduced human vascular smooth muscle cells proliferation and migration

Introduction and Objective: Cardiovascular diseases (CVD) are the leading cause of death globally. Atherosclerosis is a common CVD which can lead to the deadliest heart failure. Increasing evidence showed that abnormal vascular smooth muscle cells (VSMC) proliferation and migration constitute the main pathological basis of atherosclerosis. These events are potently stimulated by platelet-derived growth factor (PDGF), causing phenotypic switching of VSMC from a mature, quiescent phenotype to a proliferative, migratory phenotype which is commonly observed in the development of atherosclerosis. Furthermore, study have revealed that PDGF elevates the concentration of reactive oxygen species (ROS) which stimulates VSMC proliferation and migration. Pharmacological treatment for atherosclerosis is often an ongoing, long-term regimen that may have adverse effect to an individual. Thus, alternative therapy based on natural products can potentially be the frontier in atherosclerosis treatment. Interestingly, previous study revealed that Malaysian Tualang Honey (MTH) is capable of protecting vascular endothelial cells from inflammation. However, little is known on the effect of MTH on the PDGF-induced VSMC proliferation and migration. Therefore, the present study aimed to determine the antioxidant, anti-proliferative and anti-migratory effects of MTH in PDGF-induced VSMC. Methodology: VSMC were treated with increasing concentrations of MTH (0.001–10%) for 24 hours and the cell viability were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were then be treated with non-cytotoxic concentrations of MTH and induced with 20ng/mL PDGF for 72 hours to determine the proliferation rate via MTT assay. The intracellular ROS were measured in these cultured cells by dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Wound healing assay were used to determine the anti-migration activities on PDGF-induced VSMC treated with MTH. Results: Our data showed that MTH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to VSMC. Co-culture of the cells with MTH significantly inhibits the proliferation and migration of PDGF-stimulated VSMC in a concentration-dependent manner. Pre-treatment of cells with MTH prior to culturing in 20ng/mL PDGF showed a significant decrease in the production of ROS. Conclusion: This study demonstrates that MTH inhibits VSMC proliferation and migration by suppressing the production of ROS which constitute the pharmacological basis of anti-atherosclerotic action. Therefore, MTH potentially can be a promising therapeutic agent in the treatment of atherosclerosis.