Eremantholide C from aerial parts of Lychnophora trichocarpha, as drug candidate: fraction absorbed prediction in humans and BCS permeability class determination

Abstract

Background

Lychnophora trichocarpha (Spreng.) Spreng. ex Sch.Bip has been used in folk medicine to treat pain, inflammation, rheumatism and bruises. Eremantholide C, a sesquiterpene lactone, is one of the substances responsible for the anti-inflammatory and anti-hyperuricemic effects of L. trichocarpha.

Objectives

Considering the potential to become a drug for the treatment of inflammation and gouty arthritis, this study evaluated the permeability of eremantholide C using in situ intestinal perfusion in rats. From the permeability data, it was possible to predict the fraction absorbed of eremantholide C in humans and elucidate its oral absorption process.

Methods

In situ intestinal perfusion studies were performed in the complete small intestine of rats using different concentrations of eremantholide C: 960 μg/ml, 96 μg/ml and 9.6 μg/ml (with and without sodium azide), in order to verify the lack of dependence on the measured permeability as a function of the substance concentration in the perfusion solutions.

Results

Eremantholide C showed Peff values, in rats, greater than 5 × 10−5 cm/s and fraction absorbed predicted for humans greater than 85%. These results indicated the high permeability for eremantholide C. Moreover, its permeation process occurs only by passive route, because there were no statistically significant differences between the Peff values for eremantholide C.

Conclusion

The high permeability, in addition to the low solubility, indicated that eremantholide C is a biologically active substance BCS class II. The pharmacological activities, low toxicity and biopharmaceutics parameters demonstrate that eremantholide C has the necessary requirements for the development of a drug product, to be administered orally, with action on inflammation, hyperuricemia and gout.

Graphical abstract

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Acknowledgments

The authors would like to thank Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Agência Nacional de Vigilância Sanitária (Anvisa) companies and Universidade Federal de Ouro Preto (Auxílio Pesquisador/PROPP/UFOP 2018 and 2019) for financial support. In addition, the authors would like to acknowledge Drª Daniela Caldeira Costa (CBIOL/NUPEB/UFOP), for donating the sodium azide, Brazilian Pharmacopeia/Fiocruz/INCQS for providing the standard drugs and Laboratório Multisusuário (CiPharma/UFOP) for providing the HPLC system. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.

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Contributions

Tamires Guedes Caldeira performed the experiments and wrote the manuscript. Dênia Antunes Saúde-Guimarães supervised and guided some experimental activities and revised the manuscript. Isabel González-Álvarez and Marival Bermejo helped in the calculation and treatment of experimental data and gave suggestions on the revision of the manuscript. Jacqueline de Souza coordinated, supervised and guided the experimental activities and revised and gave suggestions on the revision of the manuscript. The manuscript has been read and approved by all authors.

Corresponding author

Correspondence to Tamires Guedes Caldeira.

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The authors declare no conflict of interest.

Ethics approval

The experimental protocol was approved by ethics committee (Comitê de Ética no Uso de Animais - CEUA) of Universidade Federal de Ouro Preto under protocol number 2018/07. The animals were supplied by the Centro de Ciência Animal (CCA) of Universidade Federal de Ouro Preto and used, in studies, according to all the guidelines established by the Conselho Nacional de Controle de Experimentação Animal (CONCEA).

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Caldeira, T.G., Saúde-Guimarães, D.A., González-Álvarez, I. et al. Eremantholide C from aerial parts of Lychnophora trichocarpha, as drug candidate: fraction absorbed prediction in humans and BCS permeability class determination. DARU J Pharm Sci (2021). https://doi.org/10.1007/s40199-021-00397-6

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Keywords

  • Lychnophora trichocarpha
  • Eremantholide C
  • Permeability
  • In situ perfusion
  • Fraction absorbed
  • Biopharmaceutics Classification System