Potential Use of Plant Proteolytic Enzymes in Hemostasis

  • Alfonso Pepe
  • María Gabriela GuevaraEmail author
  • Florencia Rocío Tito


Hemostasis is defined as the maintenance of the fluidity of circulating blood while at the same time protecting the organism from life-threatening bleeding at sites of vascular injury. The cell-mediated system of proteolysis of plasma coagulation proteins is essential for the survival of the organism. The hemostatic mechanism has evolved as a complex system in which serine proteases with high specificity assemble on cell membrane receptors in complex with cofactor molecules. They propagate several enzymatic reactions that lead to the formation of a thrombus that stop bleedings. It can be divided into the processes of platelet plug formation, blood coagulation, anticoagulation, and fibrinolysis (Walsh and Ahmad 2002).


Pro-coagulants Anticoagulant activity Fibrinolytic activity Fibrin(ogen)olytic activity 


  1. Antão CM, Malcata FX (2005) Plant serine proteases: biochemical, physiological and molecular features. Plant Physiol Biochem 43:637–650. Scholar
  2. Badgujar SB (2014) Evaluation of hemostatic activity of latex from three Euphorbiaceae species. J Ethno Pharmacol 151(1):733–739CrossRefGoogle Scholar
  3. Caldwell SH, Hoffman M, Lisman T et al (2006) Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 44:1039–1046. Scholar
  4. Choi J, Kim D, Park S et al (2014) Novel thrombolytic protease from edible and medicinal plant Aster yomena (Kitam.) Honda with anticoagulant activity: Purification and partial characterization. J Biosci Bioeng 118:372–377. Scholar
  5. Dzik WS (2012) Reversal of drug-induced anticoagulation: old solutions and new problems. Transfusion 52(1):45S–55S. Scholar
  6. Feijoo-Siota L, Villa TG (2010) Native and biotechnologically engineered plant proteases with industrial applications. Food Bioprocess Technol 4:1066–1088. Scholar
  7. Fonseca KC, Morais NCG, Queiroz MR et al (2010) Purification and biochemical characterization of Eumiliin from Euphorbia milii var. hislopii latex. Phytochemistry 71:708–715. Scholar
  8. Gangaraju S, Manjappa B, Subbaiah GK et al (2015) Jackfruit (Artocarpus heterophyllus) seed extract exhibits fibrino(geno)lytic activity. Pharmacogn J 7:171–177. Scholar
  9. Greaves M, Preston FE (2001) Approach to the bleeding patient. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN (eds) Haemostasis and thrombosis: basic principles and clinical practice. Lippincott Williams and Wilkins, PhiladelphiaGoogle Scholar
  10. Kim J, Rudella A, Ramirez Rodriguez V et al (2009) Subunits of the plastid ClpPR protease complex have differential contributions to embryogenesis, plastid biogenesis, and plant development in Arabidopsis. Plant Cell 21:1669–1692. Scholar
  11. Kim D-W, Choi J-H, Park S-E et al (2015) Purification and characterization of a fibrinolytic enzyme from Petasites japonicus. Int J Biol Macromol 72:1159–1167. Scholar
  12. Lazebnik YA, Takahashi A, Moir RD et al (1995) Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution. Proc Natl Acad Sci U S A 92:9042–9046. Scholar
  13. Pallister C, Watson M (2011) Haematology. Scion Publishing Ltd, BanburyGoogle Scholar
  14. Patel GK, Kawale AA, Sharma AK (2012) Purification and physicochemical characterization of a serine protease with fibrinolytic activity from latex of a medicinal herb Euphorbia hirta. Plant Physiol Biochem 52:104–111. Scholar
  15. Peeters H (1980) Protides of the biological fluids: proceedings of the twenty-eighth colloquium. Pergamon, OxfordGoogle Scholar
  16. Pepe A, Frey ME, Muñoz F et al (2016) Fibrin(ogen)olytic and antiplatelet activities of a subtilisin-like protease from Solanum tuberosum (StSBTc-3). Biochimie 125:163–170. Scholar
  17. Ramos MV, Viana CA, Silva AFB et al (2012) Proteins derived from latex of C. procera maintain coagulation homeostasis in septic mice and exhibit thrombin- and plasmin-like activities. Naunyn Schmiedeberg’s Arch Pharmacol 385:455–463. Scholar
  18. Rodríguez-Herva JJ, González-Melendi P, Cuartas-Lanza R et al (2012) A bacterial cysteine protease effector protein interferes with photosynthesis to suppress plant innate immune responses. Cell Microbiol 14:669–681. Scholar
  19. Satish A, Sairam S, Ahmed F, Urooj A (2012) Moringa oleifera Lam.: protease activity against blood coagulation cascade. Pharmcogn Res 4:44–49. Scholar
  20. Shivalingu BR, Vivek HK, Priya BS et al (2016) Purification and characterization of novel fibrin(ogen)olytic protease from Curcuma aromatica Salisb.: role in hemostasis. Phytomedicine 23:1691–1698. Scholar
  21. Shivaprasad HV, Rajesh R, Nanda BL et al (2009) Thrombin like activity of Asclepias curassavica L. latex: action of cysteine proteases. J Ethnopharmacol 123:106–109. Scholar
  22. Shivaprasad HV, Rajaiah R, Frey BM et al (2010) “Pergularain e I”--a plant cysteine protease with thrombin-like activity from Pergularia extensa latex. Thromb Res 125:e100–e105. Scholar
  23. Singh KA, Nayak MK, Jagannadham MV, Dash D (2011) Thrombolytic along with anti-platelet activity of crinumin, a protein constituent of Crinum asiaticum. Blood Cells Mol Dis 47:129–132. Scholar
  24. Singh MK, Usha R, Hithayshree KR, Bindhu OS (2015) Hemostatic potential of latex proteases from Tabernaemontana divaricata (L.) R. Br. ex. Roem. and Schult. and Artocarpus altilis (Parkinson ex. F.A. Zorn) Forsberg. J Thromb Thrombolysis 39:43–49. Scholar
  25. Siritapetawee J, Thumanu K, Sojikul P, Thammasirirak S (2012) A novel serine protease with human fibrino(geno)lytic activities from Artocarpus heterophyllus latex. Biochim Biophys Acta 1824:907–912. Scholar
  26. Siritapetawee J, Sojikul P, Klaynongsruang S (2015) Biochemical characterization of a new glycosylated protease from Euphorbia cf. lactea latex. Plant Physiol Biochem 92:30–38. Scholar
  27. Versteeg HH, Heemskerk JWM, Levi M, Reitsma PH (2013) New fundamentals in hemostasis. Physiol Rev 93:327–358. Scholar
  28. Walsh PN, Ahmad SS (2002) Proteases in blood clotting. Essays Biochem 38:95–111. Scholar
  29. Wittenbach VA, Lin W, Hebert RR (1982) Vacuolar localization of proteases and degradation of chloroplasts in mesophyll protoplasts from senescing primary wheat leaves. Plant Physiol 69:98–102. Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Biological Research Institute, National Council of Scientific and Technique Research (CONICET)University of Mar del Plata (UNMDP)Mar del PlataArgentina

Personalised recommendations