Chromatographic profile, in silico and in vivo study of the pharmacokinetic and toxicological properties of major constituent present in kefir, the kefiran

Susy Érika de Lima Barros; Henrique Barros de Lima; Leandra Karoline Alves Gonçalves; Lenir Cabral Correia; Maiara de Fátima de Brito Brito; Mariana Pegrucci Barcelos; Guilherme Martins Silva; Carlos Henrique Tomich de Paula da Silva; Rafael Garrett da Costa; Rodrigo Alves Soares Cruz; José Carlos Tavares Carvalho; Lorane Izabel da Silva Hage-Melim

doi:10.1093/toxres/tfac032

Chromatographic profile, in silico and in vivo study of the pharmacokinetic and toxicological properties of major constituent present in kefir, the kefiran

Toxicol Res (Camb). 2022 May 31;11(3):520-528. doi: 10.1093/toxres/tfac032. eCollection 2022 Jun.

Authors

Affiliations

¹ Laboratory of Pharmaceutical and Medicinal Chemistry (PharMedChem), Department of Biological and Health Sciences, Federal University of Amapá, 68903-419, Macapá, Amapá, Brazil.
² Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, 14040-90, Ribeirão Preto, São Paulo, Brazil.
³ Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-903, Ribeirão Preto, São Paulo, Brazil.
⁴ Metabolomics Laboratory (LabMeta, LADETEC), Instituto of Chemistry, Federal University of Rio de Janeiro (UFRJ), 21941-598 Rio de Janeiro, Rio de Janeiro, Brazil.
⁵ Phytopharmaceutical Nanobiotechnology Laboratory (NanoFito), Department of Biological and Health Sciences, Federal University of Amapá, 68903-419, Macapá, Amapá, Brazil.
⁶ Laboratory of Drug Research, Department of Biological and Health Sciences, Federal University of Amapá, 68903-419, Macapá, Amapá, Brazil.

Abstract

Kefiran is a polysaccharide present in kefir grains that have been widely explored due to its potential health benefits. The objective of this work was to characterize and quantify the components present in the ethanolic extract of milk kefir grains; to study its pharmacokinetic and toxicological properties in silico and evaluate the acute toxicity of the kefiran in zebrafish. The prediction of pharmacokinetic properties was performed by QikProp software. In silico toxicity assessment was performed using the DEREK (deductive estimate of risk from existing knowledge) software. In the chromatographic, kefiran was identified as the major component. Results showed that the kefiran had low human oral absorption and intestinal absorption its due poor solubility profile; low logP value, indicating its lipophilicity and the low MDCK and Caco-2 cells permability, and unable to cross the blood-brain barrier. Kefiran did not present any structural warning for in silico toxicity. In zebrafish, the dose of 2,000 mg/kg of kefiran produced nonsignificant alterations in the analyzed organs. It can be said then that kefiran has an acceptable degree of safety for use in the development of drugs or functional foods. Further research such as in vivo testing to confirm its pharmacological potential is currently underway.

Keywords: ADME/Tox; functional foods; in silico; kefir; kefiran; polysaccharide.