title: Thrombosis recanalization by paeoniflorin through the upregulation of urokinase‑type plasminogen activator via the MAPK signaling pathway.
abstract: Paeoniflorin, the major component of Paeonia lactiflora pall, has previously been reported to prevent thrombosis. Plasminogen activator urokinase (uPA) is a serine protease that markedly facilitates normal thrombosis resolution. Paeoniflorin and uPA have been linked to the mitogen‑activated protein kinase (MAPK) signaling pathway. In the current study, the influence of paeoniflorin on the expression of uPA was investigated and the underlying regulatory mechanism was preliminarily determined. The prothrombotic state of the model animals treated with paeoniflorin were assessed by enzyme‑linked immunosorbent assay (ELISA). Additionally, the cytotoxicity of paeoniflorin on human umbilical vein endothelial cell (HUVEC) cultures was estimated using a methyl thiazolyl tetrazolium assay and the possible pathways involved in the interaction between paeoniflorin and uPA were evaluated using western blot analysis. The ELISA results demonstrated that the levels of 6‑keto prostaglandin F1a, fibronectin and uPA were significantly upregulated by treatment with paeoniflorin compared with control (P<0.05). By contrast, the expression of fibrinogen, D‑dimer and thromboxane B2 were inhibited. With an increase in the concentration of paeoniflorin the cell viability of HUVECs decreased gradually. The results of western blot analysis demonstrated that paeoniflorin increased the phosphorylation of MAPK 14 (p38) and MAPK 8 (JNK). The present study demonstrated that paeoniflorin has the potential to improve the prethrombotic state and recanalize thrombosis by increasing the expression of uPA, which may be mediated via regulation of the p38 and JNK MAPK signaling pathways. However, this treatment effect was dependent on the concentration of paeoniflorin used, an unsuitable concentration of the agent would result in a negative effect on the anti‑thrombosis pathways.
authors.affiliation: Department of Medical Experimental Center, Zhang Zhongjing Traditional Chinese Medicine College, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China.
authors.forename: Songshan
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Medical Experimental Center, Zhang Zhongjing Traditional Chinese Medicine College, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Mao
authors.affiliation: Department of Medical Experimental Center, Zhang Zhongjing Traditional Chinese Medicine College, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Medical Experimental Center, Zhang Zhongjing Traditional Chinese Medicine College, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Medical Experimental Center, Zhang Zhongjing Traditional Chinese Medicine College, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China.
authors.forename: Junran
authors.initials: J
authors.lastname: Hou
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D013927:Thrombosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D006027:Glycosides
chemical_list: D005960:Glucosides; D048031:JNK Mitogen-Activated Protein Kinases; D039821:Monoterpenes; D014568:Urokinase-Type Plasminogen Activator; D048051:p38 Mitogen-Activated Protein Kinases; C015423:peoniflorin; D006027:Glycosides