Antiplatelet, Antithrombotic, and Fibrinolytic Activities of<i>Campomanesia xanthocarpa</i>

Klafke, Jonatas Zeni; Silva, Mariane Arnoldi da; Rossato, Mateus; Trevisan, Gabriela; Walker, Cristiani Isabel Banderó; Leal, Cláudio A.M.; Borges, Diego Olschowsky; Schetinger, Maria Rosa Chitolina; Moresco, Rafael Noal; Duarte, Marta Maria Medeiros Frescura; Santos, Adair R.S.; Viecili, Paulo Ricardo Nazário; Ferreira, Juliano

doi:10.1155/2012/954748

Cited by 56 publications

(35 citation statements)

References 38 publications

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“…Preparation of platelet-rich plasma and platelet-poor plasma Rat platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were prepared as previously described [15] . Briefly, blood samples were drawn from drug-free rats without stasis into a 3.8% sodium citrate solution (9:1, v/v).…”

Section: Animals and Human Samplesmentioning

confidence: 99%

The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

Wang

et al. 2016

Acta Pharmacol Sin

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Aim: Psm2, one of the pyrrolidinoindoline alkaloids isolated from whole Selaginella moellendorffii plants, has shown a potent antiplatelet activity. In this study, we further evaluated the antiplatelet effects of Psm2, and elucidated the underlying mechanisms. Methods: Human platelet aggregation in vitro and rat platelet aggregation ex vivo were investigated. Agonist-induced platelet aggregation was measured using a light transmission aggregometer. The antithrombotic effects of Psm2 were evaluated in arteriovenous shunt thrombosis model in rats. To elucidate the mechanisms underlying the antiplatelet activity of Psm2, ELISAs, Western blotting and molecular docking were performed. The bleeding risk of Psm2 administration was assessed in a mouse tail cutting model, and the cytotoxicity of Psm2 was measured with MTT assay in EA.hy926 cells. Results: Psm2 dose-dependently inhibited human platelet aggregation induced by ADP, U4619, thrombin and collagen with IC 50 values of 0.64, 0.37, 0.35 and 0.87 mg/mL, respectively. Psm2 (1, 3, 10 mg/kg) administered to rats significantly inhibited platelet aggregation ex vivo induced by ADP. Psm2 (1, 3, 10 mg/mL, iv) administered to rats with the A-V shunt dose-dependently decreased the thrombus formation. Psm2 inhibited platelet adhesion to fibrinogen and collagen with IC 50 values of 84.5 and 96.5 mg/mL, respectively, but did not affect the binding of fibrinogen to GPIIb/IIIa. Furthermore, Psm2 inhibited AktSer473 phosphorylation, but did not affect MAPK signaling and Src kinase activation. Molecular docking showed that Psm2 bound to phosphatidylinositol 3-kinase β (PI3Kβ) with a binding free energy of -13.265 kcal/mol. In addition, Psm2 did not cause toxicity in EA.hy926 cells and produced only slight bleeding in a mouse tail cutting model. Conclusion: Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling. Psm2 may be a lead compound or drug candidate that could be developed for the prevention or treatment of thrombotic diseases.

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Section: Animals and Human Samplesmentioning

confidence: 99%

The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

Wang

et al. 2016

Acta Pharmacol Sin

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“…In addition to its effect on cholesterol levels, this plant showed potential anti-inflammatory because reduced oxidative stress in hypercholesterolemic patients improving the levels of NOx [11]. Antiplatelet, antithrombotic, and fibrinolytic activities [12] and antioxidant [13], antidiabetic [14], antiulcer activities [15] of C. xanthocarpa leaves were scientifically demonstrated in the literature. The studies with essential oil showed anti-fungic effects [16].…”

Section: Introductionmentioning

confidence: 97%

Anti-inflammatory Evaluation and Toxicological Analysis of Campomanesia xanthocarpa Berg

et al. 2016

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Campomanesia xanthocarpa (Myrtaceae) is used in Brazilian traditional medicine against fever, diabetes, hypercholesteremic, obesity, and urinary diseases. In the present study, the compounds 2',6'-dihydroxy-3'-methyl-4'-metoxychalcone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone were identified for the first time in leaves of the C. xanthocarpa. These compounds and the hydroethanolic extract (HECX) significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. No toxicity was detected by HECX in an acute toxicity test.

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“…The hemolysis activity of spirulan was tested by a fibrinolytic activity assay . A blood clot was prepared by spontaneous coagulation of mouse blood in a test tube.…”

Section: Methodsmentioning

confidence: 99%

Spirulan from Blue‐Green Algae Inhibits Fibrin and Blood Clots: Its Potent Antithrombotic Effects

Choi

Kim

2015

J Biochem & Molecular Tox

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We investigated in vitro and in vivo fibrinolytic and antithrombotic activity of spirulan and analyzed its partial biochemical properties. Spirulan, a sulfated polysaccharide from the blue-green alga Arthrospira platensis, exhibits antithrombotic potency. Spirulan showed a strong fibrin zymogram lysis band corresponding to its molecular mass. It specifically cleaved Aα and Bβ, the major chains of fibrinogen. Spirulan directly decreased the activity of thrombin and factor X activated (FXa), procoagulant proteins. In vitro assays using human fibrin and mouse blood clots showed fibrinolytic and hemolytic activities of spirulan. Spirulan (2 mg/kg) showed antithrombotic effects in the ferric chloride (FeCl3 )-induced carotid arterial thrombus model and collagen and epinephrine-induced pulmonary thromboembolism mouse model. These results may be attributable to the prevention of thrombus formation and partial lysis of thrombus. Therefore, we suggest that spirulan may be a potential antithrombotic agent for thrombosis-related diseases.

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Antiplatelet, Antithrombotic, and Fibrinolytic Activities ofCampomanesia xanthocarpa

Cited by 56 publications

References 38 publications

The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

Anti-inflammatory Evaluation and Toxicological Analysis of Campomanesia xanthocarpa Berg

Spirulan from Blue‐Green Algae Inhibits Fibrin and Blood Clots: Its Potent Antithrombotic Effects

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