Yangambin and Epi-yangambin Isomers: New Purification Method from Ocotea fasciculata and First Cytotoxic Aspects Focusing on In Vivo Safety

Autor(es):Mostrar menos -

Martins, Julia ^[1] ; Coelho, Joana ^[2] ; Tadini, Maraine Catarina ^{[3, 2]} ; de Souza, Rebeca Oliveira ^[2] ; Figueiredo, Sonia Aparecida ^[1] ; Vieira Fonseca, Maria Jose ^[1] ; Perez de Albuquerque, Nayara Cristina ^[3] ; Lopes, Norberto Peporine ^[4] ; Berretta, Andresa ^[2] ; Marquele-Oliveira, Franciane ^[5] ; Moraes de Oliveira, Anderson Rodrigo ^[3]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Ciencias Farmaceut, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[2] Apis Flora Indl Coml Ltda, Lab Res Dev & Innovat, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Preto, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, NPPNS, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[5] ELEVE Sci, Lab Res Dev & Innovat, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Planta Medica; v. 86, n. 6, p. 415-424, APR 2020.
• Citações Web of Science: 0

Resumo

Ocotea fasciculata presents yangambin (YAN) and its isomer epi-yangambin (EPI-YAN) as major lignans, which are employed as the plant markers for quality control purposes and as potential pharmacological compounds. However, a gap between the pure isomers and safety and efficacy protocols is faced by the scientific community. In this context, this work aimed to report (i) a new and advantageous purifying process in a semi-preparative scale for YAN and EPI-YAN isolation from Ocotea fasciculata , and (ii) an in vitro cytotoxicity study to estimate, for the first time, the LD (50) values of the isolated epimers, as well as the influence of albumin concentration in cell culture medium. The best condition for epimers isolation was achieved in normal-phase liquid chromatography. The lignan fraction (LF), previously obtained from the plant ethanolic extract, was purified yielding 17% and 29% of YAN and EPI-YAN, respectively. The in vitro study demonstrated that YAN and EPI-YAN were safe, and only at the highest concentration studied, a decrease on cell viability was observed. The estimated LD (50) value was higher than 1612 mg/kg for both epimers. The LF, on the other hand, demonstrated an estimated LD (50) of 422 mg/kg. Lignan cytotoxicity studies also evidenced that the higher cell viability was related to the higher concentration of fetal bovine serum as a source of albumin in medium. This is the first time the LD (50) and safety of the isolated epimers were estimated, opening up great perspectives of success in in vivo studies. (AU)

• Processo FAPESP: 14/50410-3 - Desenvolvimento de um medicamento de base nanotecnológica oriundo da biodiversidade brasileira para tratamento de Leshmaniose
• Beneficiário: Franciane Marquele de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisa Inovativa em Pequenas Empresas - PIPE
• Processo FAPESP: 16/07597-0 - Desenvolvimento de métodos cromatográficos/eletroforéticos para posterior aplicação em estudos in vitro de inibição enzimática e interações medicamentosas de pesticidas quirais
• Beneficiário: Anderson Rodrigo Moraes de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07534-4 - Desenvolvimento de métodos cromatográficos/eletroforéticos para posterior aplicação em estudos in vitro de inibição enzimática e predição de interações medicamentosas de praguicidas quirais - Fase 2
• Beneficiário: Anderson Rodrigo Moraes de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular