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Plant latex thrombin-like cysteine proteases alleviates bleeding by bypassing factor VIII in murine model
Chandrasekaran Ramakrishnan
Published in Wiley-Liss Inc.
2019
PMID: 30861186
Volume: 120
   
Issue: 8
Pages: 12843 - 12858
Abstract
Hemostasis is a tightly regulated process which maintains a fluid state of blood within the vasculature and provides thrombotic response upon tissue injury. Various scientific studies have implicated the role of plant latex proteases in hemostasis using in vitro experiments. However, in vivo models substantiate their role in hemostasis. Therefore, in the present study, the effect of plant latex thrombin-like proteases (PTLPs) on hemostasis was investigated systematically using mice tail bleeding as a preclinical model. In this direction, latex protease fractions (LPFs), which showed potent thrombin-like activity, were selected as they act directly on fibrinogen to form clot and quickly stop bleeding. Thrombin-like activity was exhibited mainly by cysteine proteases. Calotropis gigantea, Carica papaya, Jatropha curcas, Oxystelma esculentum, Tabernaemontana divaricata, and Vallaris solanacea LPFs and papain from C. papaya latex significantly reduced bleeding on a topical application in normal and aspirin administered mice. In addition, PTLPs accelerated the clotting of factor VIII deficient plasma, while, papain brought back the clotting time to normal levels acting like a bypassing agent. Further, papain failed to show activity in the presence of specific cysteine protease inhibitor iodoacetic acid; confirming protease role in all the activities exhibited. At the tested dose, PTLPs except C. gigantea did not show toxicity. Further, structural and sequence comparison between PTLPs and human thrombin revealed structural and sequence dissimilarity indicating their unique nature. The findings of the present study may open up a new avenue for considering PTLPs including papain in the treatment of bleeding wounds. © 2019 Wiley Periodicals, Inc.
About the journal
JournalData powered by TypesetJournal of Cellular Biochemistry
PublisherData powered by TypesetWiley-Liss Inc.
ISSN07302312
Open AccessNo
Concepts (38)
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    ACETYLSALICYLIC ACID
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    Anticoagulant agent
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    BLOOD CLOTTING FACTOR 8
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    CYSTEINE PROTEINASE INHIBITOR
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    Fibrinogen
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    IODOACETIC ACID
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    PAPAIN
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    PLANT LATEX PROTEASE
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    Proteinase
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    Unclassified drug
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    ACTIVATED PARTIAL THROMBOPLASTIN TIME
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    Adult
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    Animal experiment
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    Animal model
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    Article
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    BLEEDING DISORDER
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    BLOOD CLOTTING TIME
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    CALOTROPIS GIGANTEA
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    Comparative study
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    Controlled study
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    Hemostasis
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    Histopathology
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    Human
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    JATROPHA CURCAS
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    Mouse
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    MOUSE MODEL
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    Nonhuman
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    Normal human
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    OXYSTELMA ESCULENTUM
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    PAPAYA
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    Plant
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    Priority journal
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    PROTEIN CONTENT
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    PROTHROMBIN TIME
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    TABERNAEMONTANA DIVARICATA
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    THROMBOCYTE POOR PLASMA
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    TOPICAL TREATMENT
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    VALLARIS SOLANACEA