DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20151355

Anticoagulant and antiplatelet properties of the latex of unripe fruits of Carica papaya L. (Caricaceae)

Frederick Asare, George Asumeng Koffuor, Wilson B. Nyansah, Linda Gyanfosu, Akua A. Abruquah

Abstract


Background: Anticoagulants have found use clinically in the management of coagulation disorders. The aim of this study therefore was to ascertain the anticoagulant and antiplatelet properties of the latex of the unripe fruits of Carica papaya (CPUFL) using in vitro and in vivo models.

Methods: CPUFL was screened for phytochemicals. The time taken, for 100 μL quantities of plasma or whole blood mixed with 100, 300, and 600 μg of CPUFL and standard assay reagents, to form clots in the prothrombin time (PT), activated partial thromboplastin time (aPTT), and clotting time tests were determined (using 1 mg rivaroxaban, 50 IU heparin, or plasma as references). The time taken for cessation of induced marginal ear vein bleeding of New Zealand White rabbits pre-treated orally with either CPUFL (4-12 mg/kg), 2 mg/kg aspirin, or 1 ml/kg distilled water, or 1.5 mg/kg heparin intraperitoneally for 30 mins was also determined.

Results: Saponins, tannins, glycosides, terpenoids, flavonoids, and alkaloids were present in CPUFL. Treatment with CPUFL (100-600 µg), increased both PT and aPTT significantly (p≤0.01-0.0001). There was also a significant increase (p≤0.0001) in clotting time of whole blood at 600 µg/100 µL. CPUFL treatment (4, 8, and 12 mg/kg) showed a dose-dependent increase (p≤0.0001) in bleeding time. Effect between CPUFL, heparin, and aspirin treatment were not significantly different.

Conclusion: The latex of unripe fruits of C. papaya L. exhibited anticoagulant and antiplatelet properties suggesting its potential usefulness in the management of blood coagulation disorders.


Keywords


Activated partial thromboplastin time, Bleeding time, Clotting time, Marginal ear vein, Prothrombin time

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References


Pereira MS, Mulloy B, Mourão PA. Structure and anticoagulant activity of sulfated fucans. Comparison between the regular, repetitive, and linear fucans from echinoderms with the more heterogeneous and branched polymers from brown algae. J Biol Chem. 1999;274(12):7656-67.

Majerus PW, Tollefsen DM. Blood coagulation and anticoagulant, thrombolytic, and antiplatelet drugs. Goodman and Gilman’s the Pharmacological Basis of Therapeutics. 11th Edition, Chapter 54. New York, NY: McGraw-Hill; 2006.

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380(9859):2095-128.

Albuquerque IR, Queiroz KC, Alves LG, Santos EA, Leite EL, Rocha HA. Heterofucans from Dictyota menstrualis have anticoagulant activity. Braz J Med Biol Res. 2004;37(2):167-71.

Samama MM, Guinet C. Laboratory assessment of new anticoagulants. Clin Chem Lab Med. 2011;49(5):761-72.

Samama MM, Martinoli JL, LeFlem L, Guinet C, Plu-Bureau G, Depasse F, et al. Assessment of laboratory assays to measure rivaroxaban – an oral, direct factor Xa inhibitor. Thromb Haemost. 2010;103(4):815-25.

Hillarp A, Baghaei F, Fagerberg Blixter I, Gustafsson KM, Stigendal L, Sten-Linder M, et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. J Thromb Haemost. 2011;9(1):133-9.

Lindhoff-Last E, Samama MM, Ortel TL, Weitz JI, Spiro TE. Assays for measuring rivaroxaban: their suitability and limitations. Ther Drug Monit. 2010;32(6):673-9.

van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, et al. Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116-27.

Bielory L. Complementary and alternative interventions in asthma, allergy, and immunology. Ann Allergy Asthma Immunol. 2004;93 2 Suppl 1:S45-54.

Canini A, Alesiani D, D’Arcangelo G, Tagliatesta P. Gas chromatography-mass spectrometry analysis of phenolic compounds from Carica papaya L. leaf. J Food Composit Anal. 2007;20:584-90.

Nitsawang S, Kaulb RH, Kanasawud P. Purification of papain from Carica papaya Latex: aqueous two - phase extraction versus two-step salt precipitation. Enzyme Microb Technol. 2006;39(5):1103-7.

Kamalkumar R, Amutha R, Muthulaksmi S, Mareeswari P, Baby RW. Screening of Dioecious papaya hybrids for papain yield and enzyme activity. Res J Agric Biol Sci. 2007;3(5):447-9.

Sofowora A. Medicinal Plants and Traditional Medicine in Africa. Chichester: John Willey and Sons; 1982: 221-3.

Elg M, Carlsson S, Gustafsson D. Effects of agents, used to treat bleeding disorders, on bleeding time prolonged by a very high dose of a direct thrombin inhibitor in anesthesized rats and rabbits. Thromb Res. 2001;101(3):159-70.

Lee W, Yang EJ, Ku SK, Song KS, Bae JS. Anticoagulant activities of oleanolic acid via inhibition of tissue factor expressions. BMB Rep. 2012;45(7):390-5.

Winter Y, Richard D, Alexei K, Martin G, Wolfgang HO, Tobias B. Clinical and pharmacological properties of new oral anticoagulants for the prevention of cerebral thromboembolism: factor Xa and thrombin inhibitors. World J Neurosci. 2012;2:7-14.

Asaf T, Reuveni H, Yermiahu T, Leiberman A, Gurman G, Porat A, et al. The need for routine pre-operative coagulation screening tests (prothrombin time PT/partial thromboplastin time PTT) for healthy children undergoing elective tonsillectomy and/or adenoidectomy. Int J Pediatr Otorhinolaryngol. 2001;61(3):217-22.

Laffan M, Manning R. Investigation of haemostasis. In: Practical Haematology. India: Elsevier; 2010: 379-440.

Kinlough-Rathbone RL, Packham MA, Reimers HJ, Cazenave JP, Mustard JF. Mechanisms of platelet shape change, aggregation, and release induced by collagen, thrombin, or A23,187. J Lab Clin Med. 1977;90(4):707-19.

Katzung BG. Drugs used in disorders of coagulation. In: Basic and Clinical Pharmacology. 10th Edition. San Francisco: McGraw Hill Company; 2007: 542-60.

Janssen K, Mensink RP, Cox FJ, Harryvan JL, Hovenier R, Hollman PC, et al. Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Am J Clin Nutr. 1998;67(2):255-62.

Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G, Goldberg DM. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta. 1995;235(2):207-19.

Pace-Asciak CR, Rounova O, Hahn SE, Diamandis EP, Goldberg DM. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clin Chim Acta. 1996;246(1-2):163-82.

Guglielmone HA, Agnese AM, Núñez Montoya SC, Cabrera JL. Anticoagulant effect and action mechanism of sulphated flavonoids from Flaveria bidentis. Thromb Res. 2002;105(2):183-8.

Akiyama H, Fujii K, Yamasaki O, Oono T, Iwatsuki K. Antibacterial action of several tannins against Staphylococcus aureus. J Antimicrob Chemother. 2001;48(4):487-91.

Zhang R, Huang B, Du D, Guo X, Xin G, Xing Z, et al. Anti-thrombosis effect of diosgenyl saponins in vitro and in vivo. Steroids. 2013;78(11):1064-70.

Singh JM, Singh MD. Alkaloids of tobacco and blood coagulation: effect of nicotine on thrombin and fibrinogen. Clin Toxicol. 1975;8(1):43-52.