title: p-Terphenyl curtisian E inhibits in vitro platelet aggregation via cAMP elevation and VASP phosphorylation.
abstract: Mushrooms possess untapped source of enormous natural compounds showing anti-inflammatory, antioxidant and anti-platelet activities. Paxillus curtisii, wild mushroom, is a rich source of curtisian E (CE) reported for neuroprotective effects; however, its anti-platelet effect was unknown. Here, therefore, we investigated the anti-platelet activity of CE in rat platelets. Curtisian E (12.5-200μM) attenuated collagen (2.5μg/ml), thrombin (0.1U/ml) and ADP (10μM) induced platelet aggregation in vitro. Likewise, CE diminished intracellular calcium and adenosine triphosphate (ATP) release in collagen activated platelets. Fibrinogen binding and fibronectin adhesion to platelets were also inhibited. While CE downregulated c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and Akt dose dependently in collagen stimulated platelets, it upregulated intraplatelet cyclic adenosine monophosphate (cAMP) and vasodilator-stimulated-phosphoprotein (VASP) phosphorylation. Protein kinase A inhibitor (H-89) markedly inhibited p-VASP(157) protein expression, suggesting that cAMP-PKA-VASP(157) pathway may mediate its anti-platelet effect and thus CE could be considered as a potential anti-thrombotic agent.
authors.affiliation: Department of Animal Husbandry And Veterinary Science, University of Rajshahi, Rajshahi, Bangladesh.
authors.forename: Sordar Mohammed
authors.initials: SM
authors.lastname: Kamruzzaman
authors.forename: Taddesse
authors.initials: T
authors.lastname: Yayeh
authors.forename: Hyun Dong
authors.initials: HD
authors.lastname: Ji
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Young Sam
authors.initials: YS
authors.lastname: Kwon
authors.forename: In-Kyoung
authors.initials: IK
authors.lastname: Lee
authors.forename: Suk
authors.initials: S
authors.lastname: Kim
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Sung Dae
authors.initials: SD
authors.lastname: Kim
authors.forename: Seong-Soo
authors.initials: SS
authors.lastname: Roh
authors.forename: Bong-Sik
authors.initials: BS
authors.lastname: Yun
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D010648:Phenylacetates / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013730:Terphenyl Compounds / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D005343:Fibrinolytic Agents; D008840:Microfilament Proteins; D010648:Phenylacetates; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D013730:Terphenyl Compounds; C000588745:curtisian E; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D013917:Thrombin; D002118:Calcium
keywords: Curtisian E; Cyclic adenosine monophosphate; Mitogen activated protein kinases; Platelets; Vasodilator-stimulated-phosphoprotein