Study of Endothelial Dependent

Abstract

Hypertension and other risk factors for cardiovascular disease contribute to oxidative stress, which caused endothelial dysfunction. The most characteristic pathophysiological feature of endothelial dysfunction is a diminished nitric oxide (NO) bioavailability due to reduced endothelial NO synthase (eNOS) activity and/or increased metabolism through its interaction with superoxide anion (O2-) produced in the vascular wall. Therefore, vascular endothelial function is a strong marker for monitoring cardiovascular health on the basis that the endothelial dysfunction is the major factor of cardiovascular disease. Correction of endothelial dysfunction may be associated with reduced cardiovascular risk. This study was focused on endothelium may be a direct therapeutic target for treatment cardiovascular disease, especially hypertension. In this study was elucidated to the endothelial dependent anti-hypertensive effects of biotransformed Gwibi-tang and active compounds isolated from Styela clava

Part I. Endothelial dependent vasorelaxation by Biotransformed Gwibi-tang

Herbal medicines have been used to treat various diseases in Asian countries. One of these medicines, Gwibi-tang (GBT), is well known for its effect of treating cardiovascular disease. Biotransformed GBTs were produced by the fermentation using by Lactobacillus sp. to search metabolites on the basis of increased biological activity through its modified structure. Our hypothesis is that some metabolites in biotransformed GBT might improve anti-hypertensive effect through chemical modification. Anti-hypertensive effects of biotransformed GBT were observed by measuring angiotensin converting enzyme inhibitory activity, vasodilation and blood pressure. Biotransformed GBT, showed higher inhibitory effect on angiotensin II-converting enzyme (ACE) activity than natural GBT. Above all GB166 (fermentation using by Lactobacillus curvatus) increased endothelial-dependent vasodilation. NO synthase (NOS) inhibition abolished GB166 mediated relaxation in aorta and NO synthesis and eNOS phosphorylation (Ser 1177) were increase eNOS compared with reduced p47phox. Also, Systolic blood pressure was decreased after administration of GB166 (200 mg/kg, P.O.) in SHR. The results suggest that GB166 have improved anti-hypertensive effect for vasorelaxation by endothelial-dependent mechanism through chemical modification of natural compounds in GBT.

Part II. Vasorelaxation Effects of Partially Purified Fractions from Styela clava

The ascidian tunicate, classified as Urochordata animal, is considered to be native in the northwest Pacific region including Korea and widely distributed in northwestern Europe, North America. Styela clava, a species of tunicates, have been culturing at the southern coast of Korea and consuming as the foodstuffs. The anti-hypertensive activity of Styela clava, however, is currently unknown. The present study investigated anti-hypertension effects of active compound isolated from Styela clava. Anti-hypertensive effects of active compound isolated from Styela clava were observed by measuring indirect blood pressure and direct blood pressure using powerlab system. The study was conducted to examine the effects of angiotensin II converting enzyme (ACE) inhibitory activity and vasorelaxation response. Nitric oxide release and phosphorylation level of eNOS (Ser 1177) were measured in human vascular endothelial cells (EA.hy926 cell) cultured with active compound isolated from Styela clava. The active compound of isolated from Styela clava showed enhanced inhibitory effect on ACE activity. Vascular relaxation was improved by isolated active compound. Pre-incubation of aortic ring with L-NAME (NOS inhibitor) abolished vasorelaxation, which suggest endothelium-dependent vasorelaxation. In endothelial cells (EA.hy926 cell), NO synthesis was increase and eNOS phosphorylation (Ser 1177) was upregulated when the cells were cultured with active compound isolated from Styela clava. Systolic blood pressure was decreased after administration of compound isolated from Styela clava (50 mg/kg, I.V.) in SD-rat. The results show that active compounds of isolated from Styela clava could enhance eNOS phosphorylation and subsequent release of NO from endothelial cells. Therefore, the observed eNOS-inducing effects in response to isolated active compounds from Styela clava support a role of endothelial dependent mechanism. Overall results suggest that isolated active compound isolated from Styela clava has anti-hypertensive effect.