EFFECT OF JUSTICIA ADHATODA (MALABAR NUT) LEAF EXTRACT ON DRUG-INDUCED COAGULOPATHY IN MICE AND IN-VITRO PLATELET AGGREGATION OF HUMAN BLOOD
AbstractBackground: Justicia adhatoda is widely used in traditional medicine for treatment of menorrhagia, piles and bleeding disorders. Oral antiplatelet and anticoagulant drugs are routinely prescribed to patients with cardiovascular diseases. These drugs have one major adverse effect that they can cause spontaneous haemorrhage, which can be fatal. Development of a haemostatic agent can help in effective management of drug-induced haemorrhages. This study was devised to observe the effect of leaf extract of Justicia adhatoda on coagulation profile in mice and to evaluate its effect on in-vitro platelet aggregation. Methods: The study was divided into two parts. First part was designed to evaluate the effect of J. adhatoda leaf extract on coagulation parameters. Three drugs were used to induce coagulopathy viz., warfarin, aspirin and dabigatran. Bleeding time, platelet count, PT and APTT were estimated. Second part of this study was devised to observe the effect of J. adhatoda leaf extract on in vitro platelet aggregation of human. Percent aggregation was recorded by light transmission aggregometer for three minutes. Results Leaf extract of Justicia adhatoda decreased bleeding time from 6.1±2.36 minutes in normal control to 1.9±1.03 minutes in extract treated mice. There was no effect on the coagulation parameters. Platelet count increased significantly only in the aspirin treated group that received the extract to 540±46.8x103 /µl from 436.9±37.9x103 /µl of aspirin treated group. Platelet aggregation in vitro increased in a dose dependent manner. Conclusion: Justicia adhatoda leaf extract is effective in controlling excessive bleeding in vivo, in mice with acquired platelet defect produced by aspirin. This haemostatic effect is probably due to increased platelet aggregation as indicated by the in vitro results. Keywords: Haemostasis; Justicia adhatoda; platelet aggregation; coagulation; coagulopathy
Dzik WS. Reversal of drug‐induced anticoagulation: old solutions and new problems. Transfusion 2012;52(Suppl 1):45–55.
De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, et al. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis—Task Force on Anticoagulants in Heart Disease position paper. J Am Coll Cardiol 2012;59(16):1413–25.
Bauer KA. Reversal of antithrombotic agents. Am J Hematol 2012;87(1):119–26.
Zehnder JL. Drugs used in disorders of coagulation. In: Katzung BG, Masters SB, Trevor AJ, editors. Basic and clinical pharmacology. 12 ed. McGraw Hill, 2012; p.601–18.
De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, et al. Position paper of the ESC working group on thrombosis--Task force on anticoagulants in heart disease. J Thromb Haemost 2013;109:569–79.
Rubboli A, Becattini C, Verheugt FW. Incidence, clinical impact and risk of bleeding during oral anticoagulation therapy. World J Cardiol 2011;3(11):351–8.
Grobler C, Callum J, McCluskey SA. Reversal of vitamin K antagonists prior to urgent surgery. Can J Anaesth 2010;57(5):458–67.
Garber ST, Sivakumar W, Schmidt RH. Neurosurgical complications of direct thrombin inhibitors--catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran. J Neurosurg 2012;116(5):1093–6.
James RF, Palys V, Lomboy JR, Lamm JR, Simon SD. The role of anticoagulants, antiplatelet agents, and their reversal strategies in the management of intracerebral hemorrhage. Neurosurg Focus 2013;34(5):E6.
Giri KR, Bibek GC, Kharel D, Subba B. Screening of phytochemicals, antioxidant and silver nanoparticles biosynthesizing capacities of some medicinal plants of Nepal. J Plant Sci 2014;2(1):77–81.
Kumar A, Garg VK, Kumar R, Singh L, Chauhan S. Pharmacognostic study and establishment of quality parameters of leaves of Adhatoda vasica. linn. J Med Plant Stud 2013;1(3):35–40.
Jayapriya G, Shoba FG. Phytochemical analysis, antimicrobial efficacy and determination of bioactive components from leaves of Justicia adhatoda (linn). Asian J Plant Sci Res 2015;5(2):43–51.
Kumar KS, Debjit B, Pankaj T, Rakesh K. Indian traditional herbs Adhatoda vasica and its medicinal application. J Chem Pharm Res 2010;2(1):240–5.
Jahan Y, Siddiqui HH. Study of antitussive potential of Glycyrrhiza glabra and Adhatoda vasica using a cough model induced by sulphur dioxide gas in mice. Int J Pharm Sci Res 2012;3(6):1668–74.
National Research Council. Guide for the care and use of laboratory animals. National Academies Press; 2010.
Lambourne MD, Eltringham-Smith LJ, Gataiance S, Arnold DM, Crowther MA, Sheffield WP. Prothrombin complex concentrates reduce blood loss in murine coagulopathy induced by warfarin, but not in that induced by dabigatran etexilate. J Thromb Haemost 2012;10(9):1830–40.
Bulckaen H, Prevost G, Boulanger E, Robitaille G, Roquet V, Gaxatte C, et al. Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging. Am J Physiol Heart Circ Physiol 2008;294(4):1562–70.
Pal GK, Pravati P. Platelet Count. In: Textbook of Practical Physiology. 2nd ed. Orient Blackswan, 2006; p.114–9.
Agarwal S, Coakely M, Reddy K, Riddell A, Mallett S. Quantifying the effect of antiplatelet therapy, a comparison of the platelet function analyzer (PFA-100Â®) and modified thromboelastography (mtegâ®) with light transmission platelet aggregometry. Anesthesiology 2006;105(4):676–83.
Zhou L, Schmaier AH. Platelet aggregation testing in platelet-rich plasma. Am J Clin Pathol 2005;123(2):172–83.
Seo EJ, Lee DU, Kwak JH, Lee SM, Kim YS, Jung YS. Antiplatelet effects of Cyperus rotundus and its component (+)-nootkatone. J Ethnopharmacol 2011;135(1):48–54.
Sogut O, Erdogan MO, Kose R, Boleken ME, Kaya H, Gokdemir MT, et al. Hemostatic efficacy of a traditional medicinal plant extract (ankaferd blood stopper) in bleeding control. Clin Appl Thromb Hemost 2015;21(4):348–53.
Wu S, Huang Z, Yue J, Liu D, Wang T, Ezanno P, et al. The efficient hemostatic effect of Antarctic krill chitosan is related to its hydration property. Carbohydr Polym 2015;132:295–303.
Machlus KR, Italiano JE. The incredible journey: From megakaryocyte development to platelet formation. J Cell Biol 2013;201(6):785–96.
Atal CK, Sharma ML, Khajuria A, Kaul A, Arya RK. Thrombopoietic activity of vasicine hydrochloride. Indian J Exp Biol 1982;20(9):704–9.
Jiao Y, Chen PH, Xiong AZ, Wang ZT, Tsim KWK, Chou GX, et al. Evaluation of hemostatic and antiinflammatory activities of extracts from different Lagochilus species in experimental animals: comparison of different extractives and sources. Phytother Res 2015;29(1):22–9.
Banerjee D, Mazumder S, Sinha AK. Involvement of nitric oxide on calcium mobilization and arachidonic acid pathway activation during platelet aggregation with different aggregating agonists. Int J Biomed Sci 2016;12(1):25–6.
Khan N, Farooq AD, Sadek B. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists. Drug Des Dev Ther 2015;9(1):3497–506.
Atal CK, Chandhoke N. Chemistry and pharmacology of vasicine: A new oxytocic and abortifacient. Reg Res Lab Jammu 1980;127–38.
Chandhoke N. Vasicine, the alkaloid of Adhatoda vasica. Indian Drug 1982;24(9):425–6.