ANTICOAGULANT AND ANTIPLATELET ACTIVITIES OF JACKFRUIT (ARTOCARPUS HETEROPHYLLUS) SEED EXTRACT
Keywords:Jackfruit Seeds, Moraceae, Anticoagulant activity, Ant platelet activity
Objective: The current study focuses on the anticoagulant and antiplatelet activities of aqueous seed extract of Jackfruit (AqSEJ).
Methods: Anticoagulant effect of AqSEJ was tested using plasma recalcification time, mouse tail bleeding time, Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT). Antiplatelet activity was examined by platelet aggregation studies using agonists such as ADP, Collagen and Epinephrine.
Results: The AqSEJ enhanced the clotting time of citrated human plasma from control 200Â±10 s to 740Â±14 s. The anticoagulant activity of AqSEJ was further strengthened by in-vivo mouse tail bleeding assay. The i. v. injection of AqSEJ significantly prolonged the bleeding time in a dose dependent manner. The recorded bleeding time was>10 min (P<0.01) at the concentration of 30 Î¼g against the PBS treated control of 1.48Â±0.10 min with the IC50 values 37.5 Î¼g/ml and 47.5 Î¼g/ml respectively. Interestingly, AqSEJ specifically prolonged the clot formation process of only APTT but not PT, revealing the anticoagulation triggered by the extract could be due to its interference in an intrinsic pathway of the blood coagulation cascade. Furthermore, AqSEJ inhibited the agonists such as ADP, epinephrine and collagen induced platelet aggregation of about 66.7%, 39.2% and 37.0% respectively at the concentration of 200 Î¼g.
Conclusion: AqSEJ showed anticoagulant and antiplatelet activities. Hence, it may serve as a better alternative for thrombotic disorders.Â
Leng GC, Lee AJ, Fowkes FG, Whiteman M, Dunbar J, Housley E, et al. Incidence, natural history and cardiovascular events in symptomatic and asymptomatic peripheral arterial disease in the general population. Int J Epidemiol 1996;25:1172-81.
Anand S, Shivashankar R, Ali MK, Kondal D, Binukumar B, Montez-Rath ME, et al. Prevalence of chronic kidney disease in two major Indian cities and projections for associated cardiovascular disease. Kidney Int 2015;88:178-85.
Rosendaal FR, Cannegieter SC, van der Meer FJ, BriÃ«t E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemostasis 1993;69:236-9.
A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE steering committee. Lancet 1996;348:1329-39.
Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002;347:969-74.
Antman EM, Van de Werf F. Pharmacoinvasive therapy: the future of treatment for ST-elevation myocardial infarction. Circulation 2004;109:2480-6.
Bhat AV, Pattabiraman TN. Protease inhibitors from jackfruit seed (Artocarpusintegrifolia). J Biosci 1989;14:351-65.
Pineau N, Aucouturier P, Brugier JC, Preud'homme JL. Jacalin: a lectinmitogenic for human CD4 T lymphocytes. Clin Exp Immunol 1990;80:420-5.
Coltri KC, Oliveira LL, Pinzan CF, Vendruscolo PE, Martinez R, Goldman MH, et al. Therapeutic administration of KM+lectin protects mice against paracoccidioides brasiliensis infection via interleukin-12 production in a toll-like receptor 2-dependent mechanism. Am J Pathol 2008;173:423-32.
Omale J, Friday E. Phytochemical composition, bioactivity and wound healing potential of Euphorbia Heterophylla (Euphorbiaceae) leaf extract. Int J Pharm Biomed 2010;1:54â€“63.
Kely CC, Leandro LO, Camila FP, PatrÃcia EV, Roberto M. Therapeutic administration of KM+lectin protects mice against Paracoccidioides brasiliensis infection via interleukin-12. Am J Pathol 2008;173:423-32.
Morton J. Fruits of warm climates. Julia F. Morton, Miami, Florida; 1987. Available from: http://www.hort.purdue.edu/newcrop/morton/jackfruit_ars.html. [Last accessed on 2015 Jun 05].
Sowmyashree G, Bhagyalakshmi M, Girish KS, Kemparaju K, Rangaiah SM, Jane HP, et al. Jackfruit (Artocarpush eterophyllus) seed extract exhibits fibrino (geno)lytic activity. Pharmacogn J 2015;7:171-7.
Quick AJ. The prothrombin in hemophilia and obstructive jaun-dice. J Biol Chem 1935;107:73-85.
Denis C, Methia N, Frenette PS. A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci 1998;95:9524-9.
Ardlie NG, Han P. Enzymatic basis for platelet aggregation and release: the significance of the â€˜platelet atmosphereâ€™ and the relationship between platelet function and blood coagulation. J Haematol 1974;26:331â€“56.
Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962;194:27â€“9.
Karpatkin S, Garg SK, Siskind GW. Autoimmune thrombocytopenic purpura and the compensated thrombocytolytic state. Am J Med 1971;51:1â€“4.
Li Y, Woo V, Bose R. Platelet hyperactivity and abnormal Ca2Ã¾ homeostasis in diabetes mellitus. Am J Physiol: Heart Circ Physiol 2001;280:1480â€“9.
Barja G. The quantitative measurement of H2O2 generation in isolated mitochondria. J Bioenerg Biomembr 2002;34:227â€“33.
Asadi H, Yan B, Dowling R, Wong S, Mitchell P. Advances in medical revascularization treatments in acute ischemic stroke. Thrombosis 2014. doi.org/10.1155/2014/714218. [Article in Press]
Larsson LJ, Frisch EP, TÃ¶rneke K, Lindblom T, BjÃ¶rk I. Properties of the complex between alpha 2-macroglobulin and brinase, a proteinase from Aspergillusoryzae with thrombolytic effect. Thromb Res 1988;49:55-68.
Anand SX, Kim MC, Kamran M, Sharma SK, Kini AS, Fareed J, et al. Comparison of plateletfunction and morphology in patients undergoing percutaneous coronary intervention receiving bivalirudin versus unfractionated heparin versus clopidogrel pretreatment and bivalirudin. Am J Cardiol 2007;100:417-24.
Militaru FC, Vesa SC, Pop TR, Buzoianu AD. Pharmacogenetics aspects of oral anticoagulants therapy. J Med Life 2015;8:171-5.
Coetzee C, Levendal RV, van de Venter M, Frost CL. Anticoagulant effects of a Cannabis extract in an obese rat model. Phytomedicine 2007;14:333-7.
Hai YZ, Jun Li H, Shu, Yue Juan N, Min JQ. A new dicoumarin and anticoagulant activity from Viola yedoensis Makino. Fitoterapia 2009;80:283-5.
Rita M, Dhananjay M. Evaluation of anticoagulant activity aqueous and ethenolic extracts and their isolated phytochemicals of some medicinal plants. Int J Pharm Pharm Sci 2012;4:498-500.
Jung JL, Taesoo K, Won KC, Jin YM. Antithrombotic and antiplatelet activities of Soshiho-tang extract. BMC Complementary Altern Med 2013;13:137-41.
Siritapetawee J, Thumanu K, Sojikul P, Thammasirirak S. A novel serine protease with fibrino (geno) lytic activities from Artocarpus heterophyllus latex. Biochim Biophys Acta 2012;1824:907-12.
Rajesh R, Nataraju A, Gowda CDR, Frey BM, Frey FJ, Vishvanath BS. Purification and characterization of a 34-kDa, heat stable glycoprotein from Synadeniumgrantii latex: action on human fibrinogen and fibrin clot. Biochimie 2006;88:1313-22.
Shivaprasad HV, Riyaz M, Venkatesh Kumar R, Dharmappa KK, Tarannum S, Siddesha JM, et al. Cysteine proteases from the Asclepiadaceae plants latex exhibited thrombin and plasmin like activities. J Thromb Thrombolysis 2009;28:3304-8.