Inhibitory effect of Angelica gigas on cold-induced RhoA activation in vascular cells

Abstract

The herbal extract Angelica gigas (AG) has been applied as a vasodilating agent for patients suffering from vascular diseases for many years; however, the underlying mechanism has not been fully elucidated. The present study hypothesized that the anti-vasoconstrictive effect of AG may be effective in the treatment of abnormal cold-mediated vasospasms that occur in Raynaud's phenomenon (RP). The effect of AG on the activity of ras homolog gene family member A (RhoA) was investigated in cold-exposed vascular cells. Vascular cells were pretreated to AG, followed by a warm (37 degrees C) or cold (25 degrees C) incubation for 30 min and investigated with western blotting, ELISA and confocal microscopy. Cold treatment induced the activation of RhoA in pericytes and vascular endothelial cells, however this was reduced by treatment with AG. Furthermore, AG treatment reduced the endothelin-1 (ET-1)-mediated RhoA activation in pericytes; however, cold-induced ET-1 production by vascular endothelial cells was not affected by treatment with AG. In addition, AG treatment suppressed the formation of stress fibers and focal adhesion complexes, and the cold-induced phosphorylation of focal adhesion kinase, proto-oncogene tyrosine-protein kinase Src and extracellular signal-related kinase. Therefore, AG treatment demonstrated an ability to reduce cold-induced RhoA activation in pericytes and vascular endothelial cells, and attenuated ET-1-mediated RhoA activation in pericytes. In conclusion, the present study indicated that AG may be useful for the treatment of RP.