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Amarogentin, a secoiridoid glycoside, abrogates platelet activation through PLC γ 2-PKC and MAPK pathways.

Yen TL, Lu WJ, Lien LM, Thomas PA, Lee TY, Chiu HC, Sheu JR, Lin KH - Biomed Res Int (2014)

Bottom Line: It also inhibits in vivo thrombus formation in mice.In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP.Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.

ABSTRACT
Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60  μM) inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLC) γ2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLC γ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

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Related in: MedlinePlus

Effects of amarogentin on cyclic nucleotides in human platelets and on thrombus formation in mice. (a) Washed platelets (3.6 × 108 cells/mL) were preincubated with 10 μM nitroglycerin (NTG), 0.5 nM prostaglandin E1 (PGE1), or 60 μM amarogentin with or without 10 μM ODQ or 100 μM SQ22536, followed by treatment with 1 μg/mL collagen to induce platelet aggregation. ((b) and (c)) Mice were administered 0.5% DMSO (solvent control; ctl) and amarogentin (9- or 18 mg/kg). Then, mesenteric venules were selected and irradiated to induce microthrombus formation. The data in the bar graphs are presented as the mean ± SEM of the occlusion time which is seconds (n = 5). **P < 0.01 compared with the individual solvent control group (ctl).
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fig4: Effects of amarogentin on cyclic nucleotides in human platelets and on thrombus formation in mice. (a) Washed platelets (3.6 × 108 cells/mL) were preincubated with 10 μM nitroglycerin (NTG), 0.5 nM prostaglandin E1 (PGE1), or 60 μM amarogentin with or without 10 μM ODQ or 100 μM SQ22536, followed by treatment with 1 μg/mL collagen to induce platelet aggregation. ((b) and (c)) Mice were administered 0.5% DMSO (solvent control; ctl) and amarogentin (9- or 18 mg/kg). Then, mesenteric venules were selected and irradiated to induce microthrombus formation. The data in the bar graphs are presented as the mean ± SEM of the occlusion time which is seconds (n = 5). **P < 0.01 compared with the individual solvent control group (ctl).

Mentions: As shown in Figure 4(a), both ODQ (10 μM) and SQ22536 (100 μM) significantly reversed the inhibition of platelet aggregation mediated by nitroglycerin (10 μM)- and PGE1 (0.5 nM), respectively. However, these inhibitors do not reverse the amarogentin (60 μM)-mediated inhibition of collagen-induced platelet aggregation, which indicates that cyclic AMP (cAMP) and cyclic GMP (cGMP) are not involved in the antiplatelet effects of amarogentin.


Amarogentin, a secoiridoid glycoside, abrogates platelet activation through PLC γ 2-PKC and MAPK pathways.

Yen TL, Lu WJ, Lien LM, Thomas PA, Lee TY, Chiu HC, Sheu JR, Lin KH - Biomed Res Int (2014)

Effects of amarogentin on cyclic nucleotides in human platelets and on thrombus formation in mice. (a) Washed platelets (3.6 × 108 cells/mL) were preincubated with 10 μM nitroglycerin (NTG), 0.5 nM prostaglandin E1 (PGE1), or 60 μM amarogentin with or without 10 μM ODQ or 100 μM SQ22536, followed by treatment with 1 μg/mL collagen to induce platelet aggregation. ((b) and (c)) Mice were administered 0.5% DMSO (solvent control; ctl) and amarogentin (9- or 18 mg/kg). Then, mesenteric venules were selected and irradiated to induce microthrombus formation. The data in the bar graphs are presented as the mean ± SEM of the occlusion time which is seconds (n = 5). **P < 0.01 compared with the individual solvent control group (ctl).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4020542&req=5

fig4: Effects of amarogentin on cyclic nucleotides in human platelets and on thrombus formation in mice. (a) Washed platelets (3.6 × 108 cells/mL) were preincubated with 10 μM nitroglycerin (NTG), 0.5 nM prostaglandin E1 (PGE1), or 60 μM amarogentin with or without 10 μM ODQ or 100 μM SQ22536, followed by treatment with 1 μg/mL collagen to induce platelet aggregation. ((b) and (c)) Mice were administered 0.5% DMSO (solvent control; ctl) and amarogentin (9- or 18 mg/kg). Then, mesenteric venules were selected and irradiated to induce microthrombus formation. The data in the bar graphs are presented as the mean ± SEM of the occlusion time which is seconds (n = 5). **P < 0.01 compared with the individual solvent control group (ctl).
Mentions: As shown in Figure 4(a), both ODQ (10 μM) and SQ22536 (100 μM) significantly reversed the inhibition of platelet aggregation mediated by nitroglycerin (10 μM)- and PGE1 (0.5 nM), respectively. However, these inhibitors do not reverse the amarogentin (60 μM)-mediated inhibition of collagen-induced platelet aggregation, which indicates that cyclic AMP (cAMP) and cyclic GMP (cGMP) are not involved in the antiplatelet effects of amarogentin.

Bottom Line: It also inhibits in vivo thrombus formation in mice.In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP.Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Medical Sciences and Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.

ABSTRACT
Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60  μM) inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLC) γ2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLC γ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

Show MeSH
Related in: MedlinePlus