title: 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˚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 α2c‑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.
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Kangwook
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, Korea National University of Transportation, Chungbuk 368‑701, Republic of Korea.
authors.forename: Sung-Gook
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Cancer Preventive Material Development, Graduate School, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Woo
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Ah Jeong
authors.initials: AJ
authors.lastname: Kim
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Kang Min
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Korean Internal Medicine, College of Korean Medicine, Semyung University, Chungju 380‑960, Republic of Korea.
authors.forename: Ho Yeon
authors.initials: HY
authors.lastname: Go
authors.affiliation: Department of Oriental Internal Medicine, College of Korean Medicine, Sangji University, Wonju 220‑702, Republic of Korea.
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Sun
authors.affiliation: Korean Medicine Clinical Trial Center, Korean Medicine Hospital, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Tae-Hun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Korean Internal Medicine, College of Korean Medicine, Gachon University, Seongnam 461‑701, Republic of Korea.
authors.forename: Ki-Yong
authors.initials: KY
authors.lastname: Jung
authors.affiliation: Department of Korean Internal Medicine, College of Korean Medicine, Gachon University, Seongnam 461‑701, Republic of Korea.
authors.forename: You-Kyung
authors.initials: YK
authors.lastname: Choi
authors.affiliation: Department of Obsterics and Gynecology, College of Korean Medicine, Gachon University, Seongnam 461‑701, Republic of Korea.
authors.forename: Eun Mee
authors.initials: EM
authors.lastname: Lim
authors.affiliation: Department of Korean Rehabilitation Medicine, College of Korean Medicine, Gachon University, Seongnam 461‑701, Republic of Korea.
authors.forename: Yun-Kyung
authors.initials: YK
authors.lastname: Song
authors.affiliation: Department of Korean Internal Medicine, College of Korean Medicine, Gachon University, Seongnam 461‑701, Republic of Korea.
authors.forename: Jong-Hyeong
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Korean Internal Medicine, College of Korean Medicine, Gachon University, Seongnam 461‑701, Republic of Korea.
authors.forename: Chan-Yong
authors.initials: CY
authors.lastname: Jun
authors.affiliation: Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea.
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
mesh_terms: D000818:Animals; D003080:Cold Temperature; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D019332:Endothelin-1 / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; D018341:Receptors, Adrenergic, alpha-2