title: Anti-thrombotic effect of a novel formula from Corni fructus with malic acid, succinic acid and citric acid.
abstract: Our previous investigation had confirmed the inhibition of platelet aggregation of a novel Corni fructus-derived formula composed of malic acid, succinic acid and citric acid with a ratio of 3:2:2. The present study was to further evaluate the anti-thrombotic effect of the formula in vivo. Mice of acute pulmonary thromboembolism, and rats of arterial thrombosis were used to determine the anti-thrombotic effect of the formula. Histology analysis of endothelium was conducted with hematoxylin and eosin stain. TXB2 , 6-K-PGF1α , cAMP, cGMP and NO in rat plasma were determined. In vitro assay of αIIbβ3 and phosphorylation of ERK1/2 were performed in ADP-treated platelet. The formula significantly reduced the recovery time and mortality rate of mice with acute pulmonary thromboembolism. Remarkably extended occlusion time, decreased thrombus weight and more integrated endothelium were observed in rat with the formula. Enhanced 6-K-PGF1α , cGMP and NO, but not TXB2 and cAMP, were demonstrated in rat plasma with treatment of the formula. Finally, the formula was shown to inhibit αIIbβ3 expression and activation of ERK1/2 in platelet. The formula shows positive anti-thrombotic effect. The direct interference on ADP activated signaling in platelet and regulation of endothelium function are two primary pathways involved in the action on thrombosis.
authors.affiliation: Department of Clinic Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210029, P.R. China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210029, P.R. China.
authors.forename: Qi-Chun
authors.initials: QC
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Bian
mesh_terms: D000818:Animals; D019343:Citric Acid / Q000494:pharmacology*; D029768:Cornus / Q000737:chemistry*; D008293:Malates / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011655:Pulmonary Embolism / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019802:Succinic Acid / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*
chemical_list: D008293:Malates; D019343:Citric Acid; C030298:malic acid; D019802:Succinic Acid
keywords: ADP; Corni fructus; anti-thrombsis; endothelium; platelet