TY - JOUR
T1 - P-Terphenyl curtisian E inhibits in vitro platelet aggregation via cAMP elevation and VASP phosphorylation
AU - Kamruzzaman, Sordar Mohammed
AU - Yayeh, Taddesse
AU - Ji, Hyun Dong
AU - Park, Ji Young
AU - Kwon, Young Sam
AU - Lee, In Kyoung
AU - Kim, Suk
AU - Oh, Seung Hyun
AU - Kim, Sung Dae
AU - Roh, Seong Soo
AU - Yun, Bong Sik
AU - Rhee, Man Hee
PY - 2013/9
Y1 - 2013/9
N2 - 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-VASP157 protein expression, suggesting that cAMP-PKA-VASP157 pathway may mediate its anti-platelet effect and thus CE could be considered as a potential anti-thrombotic agent.
AB - 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-VASP157 protein expression, suggesting that cAMP-PKA-VASP157 pathway may mediate its anti-platelet effect and thus CE could be considered as a potential anti-thrombotic agent.
KW - Curtisian E
KW - Cyclic adenosine monophosphate
KW - Mitogen activated protein kinases
KW - Platelets
KW - Vasodilator-stimulated-phosphoprotein
UR - http://www.scopus.com/inward/record.url?scp=84885311900&partnerID=8YFLogxK
U2 - 10.1016/j.vph.2013.07.002
DO - 10.1016/j.vph.2013.07.002
M3 - Article
C2 - 23872194
AN - SCOPUS:84885311900
SN - 1537-1891
VL - 59
SP - 83
EP - 89
JO - Vascular Pharmacology
JF - Vascular Pharmacology
IS - 3-4
ER -