Evaluation of the anti-Trypanosoma cruzi activity in vitro and in vivo of silibinin and silibinin in association to benznidazole

Torchelsen, Fernanda Karoline Vieira da Silva; Silva, Thaila Martins; Milagre, Matheus Marques; Silva, Rafael Rodrigues; Reis, Levi Eduardo Soares; Branquinho, Renata Tupinambá; Silva, Glenda Nicioli; de Lana, Marta

doi:10.1007/s00436-020-06944-5

Treatment and Prophylaxis - Short Communication
Published: 24 November 2020

Evaluation of the anti-Trypanosoma cruzi activity in vitro and in vivo of silibinin and silibinin in association to benznidazole

Fernanda Karoline Vieira da Silva Torchelsen¹,
Thaila Martins Silva²,
Matheus Marques Milagre¹,
Rafael Rodrigues Silva¹,
Levi Eduardo Soares Reis¹,
Renata Tupinambá Branquinho^1,3,
Glenda Nicioli Silva^1,2 &
Marta de Lana ORCID: orcid.org/0000-0002-1565-4707^1,2

Parasitology Research volume 120, pages 1511–1517 (2021)Cite this article

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Abstract

Chagas disease (CD) is endemic in Latin America. Drugs available for its treatment are benznidazole (BZ)/nifurtimox (NF), both with low efficacy in the late infection and responsible for several side effects. Studies of new drugs for CD among natural products, and using drug combinations with BZ/NF are recommended. Silibinin (SLB) is a natural compound that inhibits the efflux pump (Pgp) of drugs in host cell membranes, causes death of trypanosomatids, has anti-inflammatory activity, and was never assayed against T. cruzi. Here, in vitro and in vivo activities of SLB, SLB+BZ, and BZ against T. cruzi Y strain were evaluated. Cytotoxicity of SLB in VERO cells by the MTT method revealed IC50 of 250.22 μM. The trypanocidal activity evaluated by resazurin method in epimastigotes showed that SLB 25 μM inhibited parasite growth. SLB IC50 and selectivity index (SI) for amastigote were 79.81 μM and 3.13, respectively. SLB100+BZ10 showed higher parasite inhibition (91.44%) than SLB or BZ. Swiss mice infected with Y strain were treated with SLB, SLB+BZ, and BZ. Parasitemia was evaluated daily and 90, 180, and 240 days after treatment in surviving animals by hemoculture, blood qPCR, and after euthanasia, by qPCR in heart tissue. SLB monotherapy was not able to control the parasitemia/mortality of the animals. Parasitological negativation of 85.7–100% was observed in the experimental groups treated with SLB+BZ. Although SLB had shown activity against T. cruzi in vitro, it was not active in mice. Thus, the results of the therapeutic effect observed with SLB+BZ may be interpreted as a result from BZ action.

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Abbreviations

BZ:: Benznidazole
CD:: Chagas disease
EI:: Endocytic index
NF:: Nifurtimox
Pgp:: P-glycoprotein
SLB:: Silibinin
SI:: Selectivity index

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Acknowledgments

We thank the UFOP and CAPES undergraduate and postgraduate scholarships. Marta de Lana is a research fellow of CNPq.

Funding

This study was financially supported by the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq (Process 431413/2016-9) and Fundação de Amparo à Pesquisa do Estado de Minas Gerais-FAPEMIG (APQ-00766/16 and APQ-01160-15).

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Affiliations

Programa de Pós-Graduação em Ciências Farmacêuticas (CiPHARMA), Universidade Federal de Ouro Preto (UFOP), Campus Universitário Morro do Cruzeiro, Ouro Preto, MG, 35400-000, Brazil
Fernanda Karoline Vieira da Silva Torchelsen, Matheus Marques Milagre, Rafael Rodrigues Silva, Levi Eduardo Soares Reis, Renata Tupinambá Branquinho, Glenda Nicioli Silva & Marta de Lana
Departamento de Analises Clínicas, Escola de Farmácia, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, Brazil
Thaila Martins Silva, Glenda Nicioli Silva & Marta de Lana
Departamento de Farmácia, Escola de Farmácia, UFOP, Ouro Preto, Brazil
Renata Tupinambá Branquinho

Authors

Fernanda Karoline Vieira da Silva Torchelsen
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Thaila Martins Silva
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Matheus Marques Milagre
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Rafael Rodrigues Silva
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Levi Eduardo Soares Reis
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Renata Tupinambá Branquinho
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Glenda Nicioli Silva
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Marta de Lana
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Correspondence to Marta de Lana.

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All experiments were authorized by the ethics committee for animal experimentation of Federal University of Ouro Preto (CEUA-UFOP), Minas Gerais, Brasil, protocol 2018/16.

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Torchelsen, F.K.V.d., Silva, T.M., Milagre, M.M. et al. Evaluation of the anti-Trypanosoma cruzi activity in vitro and in vivo of silibinin and silibinin in association to benznidazole. Parasitol Res 120, 1511–1517 (2021). https://doi.org/10.1007/s00436-020-06944-5

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Received: 06 December 2019
Accepted: 25 October 2020
Published: 24 November 2020
Issue Date: April 2021
DOI: https://doi.org/10.1007/s00436-020-06944-5

Keywords

Trypanosoma cruzi
Silibinin
Benznidazole
Drug association
In vitro
In vivo