Muhammad Irfan1, Dahye Jeong1, Hyuk-Woo Kwon2, Jung-Hae Shin3, Sang-Joon Park1, Dongmi Kwak1, Tae-Hwan Kim1, Dong-Ha Lee4, Hwa-Jin Park3, Man Hee Rhee5. 1. Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea. 2. Department of Biomedical Laboratory Science, Far East University, Eumseong 27601, Republic of Korea. 3. Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gyungnam, Republic of Korea. 4. Department of Biomedical Laboratory Science, and Molecular Diagnostics Research Institute, Namseoul University, Cheonan 31020, Republic of Korea. 5. Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address: rheemh@knu.ac.kr.
Abstract
BACKGROUND & PURPOSE: Ginseng (Panax ginseng C.A. Mayer) contains saponin fractions called ginsenosides, which are thought to be the main components responsible for its various pharmacological activities. Ginsenosides have cardioprotective and antiplatelet effects. In the present study, we evaluated the effects of ginsenoside Rp3 (G-Rp3) on platelet function. METHODS: The in vitro effects of G-Rp3 were evaluated on agonist-induced human and rat platelet aggregation, while [Ca2+]i mobilization, granule secretion, integrin αIIbβ3 activation, and clot retraction were assessed in rat platelets. Its effects on vasodilator-stimulated phosphoprotein (VASP) expression, phosphorylation of MAPK signaling molecules, and PI3K/Akt activation were also studied. Moreover, the tyrosine phosphorylation of components of the P2Y12 receptor downstream signaling pathway was also examined. The in vivo effects of G-Rp3 were studied using an acute pulmonary thromboembolism model and lung histopathology. KEY RESULTS: G-Rp3 significantly inhibited collagen, ADP, and thrombin-induced platelet aggregation. G-Rp3 elevated cAMP levels and VASP phosphorylation and suppressed agonist-induced [Ca2+]i mobilization, ATP release, and P-selectin expression along with fibrinogen binding to integrin αIIbβ3, fibronectin adhesion, and clot retraction. G-Rp3 also attenuated the phosphorylation of MAPK, Src, and PLCγ2 as well as PI3K/Akt activation. Furthermore, it inhibited tyrosine phosphorylation of the Src family kinases (Src, Fyn, and Lyn) and PLCγ2 and protected mice from thrombosis. CONCLUSION AND IMPLICATION: G-Rp3 modulates agonist-induced platelet activation and thrombus formation by inhibiting granule secretion, integrin αIIbβ3 activation, MAPK signaling, and Src, PLCγ2, and PI3K/Akt activation, and VASP stimulation. Our data suggest that G-Rp3 has therapeutic potential as a treatment for platelet-related cardiovascular disorders.
BACKGROUND & PURPOSE:Ginseng (Panax ginseng C.A. Mayer) contains saponin fractions called ginsenosides, which are thought to be the main components responsible for its various pharmacological activities. Ginsenosides have cardioprotective and antiplatelet effects. In the present study, we evaluated the effects of ginsenoside Rp3 (G-Rp3) on platelet function. METHODS: The in vitro effects of G-Rp3 were evaluated on agonist-induced human and ratplatelet aggregation, while [Ca2+]i mobilization, granule secretion, integrin αIIbβ3 activation, and clot retraction were assessed in rat platelets. Its effects on vasodilator-stimulated phosphoprotein (VASP) expression, phosphorylation of MAPK signaling molecules, and PI3K/Akt activation were also studied. Moreover, the tyrosine phosphorylation of components of the P2Y12 receptor downstream signaling pathway was also examined. The in vivo effects of G-Rp3 were studied using an acute pulmonary thromboembolism model and lung histopathology. KEY RESULTS: G-Rp3 significantly inhibited collagen, ADP, and thrombin-induced platelet aggregation. G-Rp3 elevated cAMP levels and VASP phosphorylation and suppressed agonist-induced [Ca2+]i mobilization, ATP release, and P-selectin expression along with fibrinogen binding to integrin αIIbβ3, fibronectin adhesion, and clot retraction. G-Rp3 also attenuated the phosphorylation of MAPK, Src, and PLCγ2 as well as PI3K/Akt activation. Furthermore, it inhibited tyrosine phosphorylation of the Src family kinases (Src, Fyn, and Lyn) and PLCγ2 and protected mice from thrombosis. CONCLUSION AND IMPLICATION: G-Rp3 modulates agonist-induced platelet activation and thrombus formation by inhibiting granule secretion, integrin αIIbβ3 activation, MAPK signaling, and Src, PLCγ2, and PI3K/Akt activation, and VASP stimulation. Our data suggest that G-Rp3 has therapeutic potential as a treatment for platelet-related cardiovascular disorders.