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Anti-inflammatory latex proteins of the medicinal plant Calotropis procera: a promising alternative for oral mucositis treatment

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Abstract

Objective and design

Oral mucositis (OM) is an intense inflammatory reaction progressing to tissue damage and ulceration. The medicinal uses of Calotropis procera are supported by anti-inflammatory capacity. PII-IAA, a highly homogenous cocktail of laticifer proteins (LP) prepared from the latex of C. procera, with recognized pharmacological properties was tested to treat OM.

Materials and subjects

Male Golden Sirius hamsters were used in all treatments.

Treatment

The latex protein samples were injected i.p. (5 mg/Kg) 24 h before mucositis induction (mechanical trauma) and 24 h later.

Methods

Histology, cytokine measurements [ELISA], and macroscopic evaluation [scores] were performed.

Results

PII-IAA eliminated OM, accompanied by total disappearance of myeloperoxidase activity and release of IL-1b, as well as reduced TNF-a. Oxidative stress was relieved by PII-IAA treatment, as revealed by MDA and GSH measurements. PII-IAA also reduced the expression of adhesion molecules (ICAM-1) and Iba-1, two important markers of inflammation, indicating modulatory effects. Histological analyses of the cheek epithelium revealed greater deposition of type I collagen fibers in animals given PII-IAA compared with the control group. This performance was only reached when LPPII was treated with iodoacetamide (IAA), an irreversible inhibitor of proteolytic activity of cysteine proteases. The endogenous proteolytic activity of LPPII induced adverse effects in animals. Candidate proteins involved in the phytomodulatory activity are proposed.

Conclusions

Therapy was successful in treating OM with the laticifer protein fraction, containing peptidases and osmotin, from Calotropis procera. The effective candidate from the latex proteins for therapeutic use is PII-IAA.

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Abbreviations

5-FU:

5-Fluorouracil

IAA:

Iodoacetamide

ICAM-1:

Intercellular adhesion molecule 1

Iba-1:

Ionized calcium-binding adapter molecule 1

LP:

Laticifer proteins

MDA:

Malondialdehyde

OM:

Oral mucositis

PI:

Protein fraction I of laticifer proteins

LP PII or PII:

Protein fraction II of laticifer proteins

PII-IAA:

Protein fraction II treated with iodoacetamide

PIII:

Protein fraction III of laticifer proteins

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Acknowledgements

Biochemical, functional and applied studies of latex proteins were supported by grants from the following Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (304531/2015-4) and Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP). This study is part of the consortium “Molecular Biotechnology of Plant Latex”.

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Author notes

  1. The following authors of this manuscript Márcio V. Ramos, Ana Paula F. Freitas, Renata F. C. Leitão, Deiziane V. S. Costa, Gilberto S. Cerqueira, Dainesy S. Martins, Conceição S. Martins, Nylane M. N. Alencar, Larissa Barbosa N. Freitas, Gerly Anne C. Brito contributed equally to the manuscript.

Authors and Affiliations

  1. Departamento de Bioquímica e Biologia Molecular, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil

    Márcio V. Ramos & Larissa Barbosa N. Freitas

  2. Universidade da Integração Internacional da Lusofonia Afro-Brasileira (UNILAB), Redenção, Ceará, Brazil

    Ana Paula F. Freitas

  3. Departamento de Morfologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil

    Renata F. C. Leitão, Deiziane V. S. Costa, Gilberto S. Cerqueira, Conceição S. Martins & Gerly Anne C. Brito

  4. Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil

    Dainesy S. Martins & Nylane M. N. Alencar

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  1. Márcio V. Ramos
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Correspondence to Márcio V. Ramos or Gerly Anne C. Brito.

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We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

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Studies of the latex of Calotropis procera are registered (N. A689147) in the SisGen (Genetic Heritage and Associated Traditional Knowledge System), according to the current Brazilian regulations.

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Ramos, M.V., Freitas, A.P.F., Leitão, R.F.C. et al. Anti-inflammatory latex proteins of the medicinal plant Calotropis procera: a promising alternative for oral mucositis treatment. Inflamm. Res. 69, 951–966 (2020). https://doi.org/10.1007/s00011-020-01365-7

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  • DOI: https://doi.org/10.1007/s00011-020-01365-7

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