Danggui-Sayuk-Ga-Osuyu-Senggang-Tang ameliorates cold-induced vasoconstriction in vitro and in vivo

Abstract

Danggui-Sayuk-Ga-Osuyu-Senggang-Tang (DSGOST), one of the traditional Chinese medicines, has long been prescribed for patients suffering from Raynaud phenomenon (RP) in Northeast Asian countries, including China, Japan and Korea. Although a previous in vitro study from our laboratory revealed that DSGOST prevents cold (25 degrees C) -induced RhoA activation and endothelin-1 (ET-1) production in endothelial cells (ECs), the mechanisms by which DSGOST is able to alleviate the symptoms of RP have yet to be fully elucidated. The present study aimed to demonstrate that DSGOST regulates RhoA-mediated pathways in cold-exposed pericytes. In pericytes, DSGOST amplified cold-induced RhoA activation, while markedly reducing ET-1-induced RhoA activation. Additionally, DSGOST-mediated regulation of RhoA was closely associated with Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1)/testis-specific kinase 1 (TESK1)/PDXP, but not with LIM domain kinase 1/2 (LIMK1/2), cofilin and myosin light chain (MLC). Thus, DSGOST activation of RhoA/ROCK1/TESK1/PDXP in cold-exposed pericytes appeared to be crucial for treating vessel contraction. In addition, the DSGOST effect on the RhoA-mediated pathway in cold-induced human umbilical vein endothelial cells or human dermal microvascular endothelial cells was similar to that in ET-1-treated pericytes, but not in cold-induced pericytes. The results of the present study further confirmed that DSGOST inhibits cold-induced contraction of the mouse tail vein in vivo. Furthermore, DSGOST treatment reduced cold-induced expression of the alpha 2c-adrenergic receptor in mouse tail vessels. Therefore, the data in the present study suggest that DSGOST may be useful for the treatment of RP-like disease.