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Proteins derived from latex of C. procera maintain coagulation homeostasis in septic mice and exhibit thrombin- and plasmin-like activities

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Abstract

The proteins derived from the latex (LP) of Calotropis procera are well known for their anti-inflammatory property. In view of their protective effect reported in the sepsis model, they were evaluated for their efficacy in maintaining coagulation homeostasis in sepsis. Intraperitoneal injection of LP markedly reduced the procoagulation and thrombocytopenia observed in mice infected with Salmonella; while in normal mice, LP produced a procoagulant effect. In order to understand its mechanism of action, the LP was subjected to ion-exchange chromatography, and the three subfractions (LPPI, LPPII, and LPPIII) thus obtained were tested for their proteolytic effect and thrombin- and plasmin-like activities in vitro. Of the three subfractions tested, LPPII and LPPIII exhibited proteolytic effect on azocasein and exhibited procoagulant effect on human plasma in a concentration-dependent manner. Like trypsin and plasmin, these subfractions produced both fibrinogenolytic and fibrinolytic effects that were mediated through the hydrolysis of the Aα, Bβ, and γ chains of fibrinogen and α-polymer and γ-dimer of fibrin clot, respectively. This study shows that the cysteine proteases present in the latex of C. procera exhibit thrombin- and plasmin-like activities and suggests that these proteins have therapeutic potential in various conditions associated with coagulation abnormalities.

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Acknowledgements

Biochemical, functional, and applied studies of the latex from C. procera have been supported by grants from the Fundação Cearense de Apoio ao Desevolvimento Científico e Tecnológico, CNPq (Brazilian Council for Research and Development: Programs Universal and RENORBIO, and Brazil/India cooperation), and the Department of Science and Technology (V.L.K.), International Foundation for Science (M.V.R.). We are grateful to the Centre of Hematology and Hemotherapy of the State of Ceará for kindly providing the human blood samples.

Conflict of interest

The authors declare that there is no conflict of interest, and the funding source(s) had no involvement in the research design, writing, or other in aspects of this manuscript.

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Authors and Affiliations

  1. Departamento de Bioquímica e Biologia Molecular, Campus do Pici, Bloco 907, Universidade Federal do Ceará, Fortaleza, Ceará, CEP 60.451-970, Brazil

    Márcio V. Ramos, Carolina A. Viana, Ayrles F. B. Silva & Raquel S. B. Oliveira

  2. Campus Amilcar Ferreira Sobral, Universidade Federal do Piauí, Floriano, Piauí, Brazil

    Cléverson D. T. Freitas

  3. Departamento de Fisiologia e Farmacologia, Campus do Porangabuçu, Universidade Federal do Ceará, Fortaleza, Ceará, CEP 60.451-970, Brazil

    Ingrid S. T. Figueiredo & Nylane M. N. Alencar

  4. Departamento de Biologia, Campus Dois Irmãos, Universidade Federal Rural de Pernambuco, Recife, Pernambuco, CEP 52171-900, Brazil

    José V. M. Lima-Filho

  5. Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Vijay L. Kumar

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  1. Márcio V. Ramos
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  2. Carolina A. Viana
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  3. Ayrles F. B. Silva
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  4. Cléverson D. T. Freitas
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  5. Ingrid S. T. Figueiredo
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  6. Raquel S. B. Oliveira
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  7. Nylane M. N. Alencar
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  8. José V. M. Lima-Filho
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Correspondence to Márcio V. Ramos.

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Ramos, M.V., Viana, C.A., Silva, A.F.B. et al. 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 (2012). https://doi.org/10.1007/s00210-012-0733-3

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