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In vitro anticoagulant activity of selected medicinal plants: potential interactions with warfarin and development of new anticoagulants

  • Paula Mendonça Leite ORCID logo EMAIL logo , Aline Freitas , Juliana Amorim , Rita Carolina Duarte Figueiredo , Suzan Bertolucci , André Faraco , Maria Martins , Maria G. Carvalho and Rachel Castilho

Abstract

Objectives

Warfarin is the most widely used anticoagulant in the world, but it has several limitations including its narrow therapeutic range, need for dose adjustment and high potential for interactions. The simultaneous use of other drugs or even medicinal plants and certain foods could interfere with its therapeutic activity. In this context, this study aims to investigate the in vitro anticoagulant potential and phytochemical constitution of 17 plants selected from a previous clinical cross-sectional study (2014), that investigated the habits of plant utilization among patients taking warfarin.

Methods

Ethanol extracts and essential oils were evaluated, in vitro, as to their effect in the prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. Four species that presented aPTT >50 s were selected for phytochemical evaluation.

Results

Thirteen of the 17 plants selected demonstrated a significant anticoagulant effect in at least one of the evaluated parameters. Citrus sinensis (PT=14.75 and aPTT=53.15), Mentha crispa (aPTT=51.25), Mikania laevigata (PT=14.90 and aPTT=52.10), and Nasturtium officinale (aPTT=50.55) showed greater anticoagulant potential compared to normal plasma pool (PT=12.25 and aPTT=37.73). Chemical profiles of these four species were obtained, and certain compounds were identified: rosmarinic acid from M. crispa and isoorientin from N. officinale.

Conclusions

Thus, the results of this study could be a useful indicator for clinical practice towards the possibility of interaction between these plants and anticoagulants, although further clinical research is needed taking into consideration the limitations of in vitro studies. These findings also suggest that further research into the action of these plants could be of real clinical value in identifying potential alternative anticoagulant therapies.


Corresponding author: Paula Mendonça Leite, PhD, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, E-mail:

Funding source: Fundação de Amparo ã Pesquisa do Estado de Minas Gerais 10.13039/501100004901

Funding source: Conselho Nacional de Desenvolvimento Científico e Tecnológico 10.13039/501100003593

Funding source: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 10.13039/501100002322

Funding source: Pró-Reitoria de Pesquisa, Universidade Federal de Minas Gerais 10.13039/501100007375

  1. Research funding: This work was supported by grants from Pró-Reitoria de Pesquisa from Universidade Federal de Minas Gerais, Fundação de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. PML, AGF, MAPM, MGC and ROC designed the article; extracted, analyzed data and drafted the manuscript. AAF, JMA, RCD and SVB extracted and analyzed data. All authors critically reviewed the manuscript, contributed to its revision, and approved the final version submitted.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Participants signed the free and informed consent form after having received an explanation about the purpose of the research, which was conducted ethically in accordance with the World Medical Association Declaration of Helsinki and authorized by Ethics committee number CAAE 37870914.0.0000.5149).

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Received: 2021-03-11
Accepted: 2021-06-28
Published Online: 2021-07-19

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