Abstract

Morus alba (white mulberry) is native to the northern part of Korea and popularly used as a traditional medicine due to its numerous health benefits against human's disease. However, the possibility that M. alba may also affect the cardiovascular system remains unexplored. This study sought to investigate the vascular protective effects of the root bark extract of M. alba (MAE). Vascular reactivity was performed in organ baths using isolated rat thoracic aorta, while platelet derived growth factor (PDGF) induced proliferation and migration of vascular smooth muscle cells (VSMCs) were studied by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and wound healing assay, respectively. MAE evoked a concentration dependent vasorelaxation following endothelium-dependent pathway. However, vessel relaxations in response to MAE were markedly reduced after endothelium removal; treatment of endothelial nitric oxide synthase inhibitor, guanylyl cyclase inhibitor, and nonspecific potassium channel inhibitor, however, was not altered by cyclooxygenase inhibitor. Furthermore, MAE also significantly blunted contractile response to vasoconstrictor agent, phenylephrine. Taken together, the current evidence revealed that MAE is a potent endothelium-dependent vasodilator and this effect was involved in, at least in part, nitric oxide cyclic-guanosine monophosphate (NO-cGMP) pathway in combination with potassium (K+) channel activation. Moreover, MAE inhibited proliferation and migration of VSMCs induced by PDGF. Therefore, MAE could be a promising candidate of natural medicine for preventing and controlling cardiovascular diseases linked with endothelial dysfunction.

Highlights

  • In global scenario, cardiovascular diseases (CVDs) are still the major cause of morbidity and mortality in developed nations, while the prevalence is rising rapidly in underdeveloped country too [1, 2]

  • Both migration and proliferation of vascular smooth muscle cells (VSMCs) are initiated by number of inducing factors such as platelet derived growth factors (PDGF) and tumor necrosis factor alpha (TNF-α) facilitating atheroma formation in vessel wall [10]

  • Indomethacin (INDO, an inhibitor of cyclooxygenase) did not affect relaxation caused by M. alba root bark extract (MAE) (Figure 2(c)). These findings indicate that endothelium-dependent relaxation by MAE may follow nitric oxide cyclic-guanosine monophosphate (NO-cGMP) pathway including potassium channel activation

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Summary

Introduction

Cardiovascular diseases (CVDs) are still the major cause of morbidity and mortality in developed nations, while the prevalence is rising rapidly in underdeveloped country too [1, 2]. Migration of VSMCs from tunica adventitia to tunica intima followed by proliferation at that site contributes to the growth of atherosclerotic plague and restenosis [9] Both migration and proliferation of VSMCs are initiated by number of inducing factors such as platelet derived growth factors (PDGF) and tumor necrosis factor alpha (TNF-α) facilitating atheroma formation in vessel wall [10]. These days, longterm therapeutic approach to control CVDs by treatment of modern/western medicine possesses many undesirable side

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