peoniflorin and Thrombosis

The compounds of Radix Paeoniae Rubra (RPR) were isolated and identified by bioassay-guided method, and antithrombotic effects and mechanism were investigated by the acute blood stasis rat model. The RPR extract was evaluated by APTT, TT, PT, and FIB assays in vitro. Results indicated that RPR extract exhibited the anticoagulant activity. In order to find active compounds, six compounds were isolated and identified, and four compounds, paeoniflorin (Pae), pentagalloylglucose (Pen), albiflorin (Ali), and protocatechuic acid (Pro), exhibited the anticoagulant activity in vitro. Therefore, the antithrombosis effects of RPR extract and four active compounds were investigated in vivo by measuring whole blood viscosity (WBV), plasma viscosity (PV), APTT, PT, TT, and FIB. Meanwhile, the levels of TXB

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anticoagulants; Biological Assay; Bridged-Ring Compounds; Drugs, Chinese Herbal; Endothelin-1; Female; Fibrinolytic Agents; Glucosides; Hydrolyzable Tannins; Hydroxybenzoates; Male; Monoterpenes; Nitric Oxide Synthase Type III; Paeonia; Phytotherapy; Rats; Rats, Sprague-Dawley; Thrombosis; Thromboxane B2; Viscosity

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.

Topics: Animals; Blood Coagulation; Cell Proliferation; Cell Survival; Disease Models, Animal; Gene Expression Regulation; Glucosides; Human Umbilical Vein Endothelial Cells; Humans; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Signaling System; Mice; Monoterpenes; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Thrombosis; Urokinase-Type Plasminogen Activator

In a photochemical reaction microvessel thrombosis model, the anti-thrombotic effect of PT was evaluated and the results showed that PF could significantly prolong thromobosis time. The anti-thrombotic effect of PF may relate to the inhibition of arachidonic acid metabolism, the increase of t-PA activity, and the protective effect against free radical.

Topics: Animals; Arachidonic Acid; Benzoates; Bridged-Ring Compounds; Cells, Cultured; Endothelium, Vascular; Fibrinolytic Agents; Free Radical Scavengers; Free Radicals; Glucosides; Humans; Monoterpenes; Paeonia; Photochemistry; Phytotherapy; Plant Preparations; Plants, Medicinal; Rats; Rats, Wistar; Thrombosis