title: Astragaloside IV inhibits PMA-induced EPCR shedding through MAPKs and PKC pathway.
abstract: Astragaloside IV (AS-IV), a main active substance isolated from Astragalus membranaceus Bunge, has been shown to have multiple pharmacological effects. Endothelial cell protein C receptor (EPCR) is a marker of inflammation, and is also a major member of protein C (PC) anti-coagulation system. EPCR can be cut off from the cell surface by tumor necrosis factor-α converting enzyme (TACE), which is controlled through mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways. To develop novel therapeutic drug for EPCR shedding, the effect of AS-IV was studied in phorbol-12-myristate 13-acetate (PMA)-induced human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism of AS-IV action was investigated. The results showed that AS-IV could significantly inhibit PMA-induced EPCR shedding. In further study, AS-IV suppressed the expression and activity of TACE. In addition, AS-IV could decrease the phosphorylation of MAPK such as janus kinase (JNK) and p38, and inhibit activation of PKC through the prevention of non-phosphorylation and phosphorylation of specific PKC isoforms in PMA-stimulated HUVECs. These findings indicate that AS-IV may be used as a natural medicine to treat EPCR-related systemic inflammation and cardiovascular diseases by targeting MAPK and PKC pathway.
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liang
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Zhongqiong
authors.initials: Z
authors.lastname: Yin
authors.affiliation: b Department of Pharmacy , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Geng
authors.affiliation: b Department of Pharmacy , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Shu
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Song
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Yuanfeng
authors.initials: Y
authors.lastname: Zou
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Li
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Lizi
authors.initials: L
authors.lastname: Yin
authors.affiliation: c College of Science , Sichuan Agricultural University , Ya'an , PR China.
authors.forename: Guizhou
authors.initials: G
authors.lastname: Yue
authors.affiliation: b Department of Pharmacy , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Yinglun
authors.initials: Y
authors.lastname: Li
authors.affiliation: b Department of Pharmacy , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ye
authors.affiliation: a Natural Medicine Research Center, College of Veterinary Medicine , Sichuan Agricultural University , Chengdu , PR China.
authors.forename: Changliang
authors.initials: C
authors.lastname: He
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D000074283:Endothelial Protein C Receptor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D011493:Protein Kinase C / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D012503:Saponins / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate
keywords: Astragaloside IV; EPCR; HUVECs; MAPK; PKC