Influence of the Phenological State of in the Antioxidant Potential and Chemical Composition of Ageratina havanensis. Effects on the P-Glycoprotein Function.

T Garcı́a ,Cindel Cuellar,Yaiser Ávila,Wagner Vilegas,Iraida Spengler,Giulia Auriemma,Idania Rodeiro,Luca Rastrelli,Míriam Teresa Paz Lopes ,Liván Delgado-Roche ,Ingrid Márquez Hernández ,Cláudia Quintino Da Rocha

doi:10.3390/molecules25092134

Abstract

Ageratina havanensis (Kunth) R. M. King & H. Robinson is a species of flowering shrub in the family Asteraceae, native to the Caribbean and Texas. The aim of this work was to compare the quantitative chemical composition of extracts obtained from Ageratina havanensis in its flowering and vegetative stages with the antioxidant potential and to determine the effects on P-glycoprotein (P-gp) function. The quantitative chemical composition of the extracts was determined quantifying their major flavonoids by UPLC-ESI-MS/MS and by PCA analysis. The effects of the extracts on P-gp activity was evaluated by Rhodamine 123 assay; antioxidant properties were determined by DPPH, FRAP and inhibition of lipid peroxidation methods. The obtained results show that major flavonoids were present in higher concentrations in vegetative stage than flowering stage. In particular, the extracts obtained in the flowering season showed a significantly higher ability to sequester free radicals compared to those of the vegetative season, meanwhile, the extracts obtained during the vegetative stage showed a significant inhibitory effect against brain lipid peroxidation and a strong reductive capacity. This study also showed the inhibitory effects of all ethanolic extracts on P-gp function in 4T1 cell line; these effects were unrelated to the phenological stage. This work shows, therefore, the first evidence on: the inhibition of P-gp function, the antioxidant effects and the content of major flavonoids of Ageratina havanensis. According to the obtained results, the species Ageratina havanensis (Kunth) R. M. King & H. Robinson could be a source of new potential inhibitors of drug efflux mediated by P-gp. A special focus on all these aspects must be taking into account for future studies.

Highlights

Polyphenols, flavonoids, have been widely studied for their bioactive properties and their strong antioxidant effects are well noted [1,2,3]
In order to mimic the chemo-resistance in humans, the cells chosen for this research were the well-characterized mouse mammary carcinoma 4T1 cells that express multi-resistance phenotype after exposure to different anticancer drugs mediated by P-gp
To determine the cytotoxic effects of the eleven extracts obtained from Ageratina havanensis on 4T1 cells, the MTT assay was employed

Summary

Introduction

Polyphenols, flavonoids, have been widely studied for their bioactive properties and their strong antioxidant effects are well noted [1,2,3]. Some plant antioxidant polyphenols exhibit anti-neoplastic activity by multiple pathways, including their potential to intensify the action. The best recognized and the most frequent cause of the MDR involves an increased activity of ATP-binding cassette family transporters (ABC) [5]. A large number of compounds have been identified as MDR suppressors by interfering with the P-gp-mediated export of chemotherapeutic agents [6,7,8,9]. Natural antioxidants have been identified as novel potential candidates [11,12,13,14,15,16]

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