Hazard assessment of Maerua subcordata (Gilg) DeWolf. for selected endpoints using a battery of in vitro tests

Abstract

Ethnopharmacological Relevance: Maerua subcordata (Gilg) DeWolf is a medicinal and wild food plant growing mainly in east Africa. Especially its root tuber is widely used in traditional medicine to treat several infectious and chronic diseases but also in some toxicity implications like use as abortifacient. Aim of the study: the present study applied in silico and in vitro tests to identify possible hazards of M. subcordata (fruit, leaf, root, seed) methanol extracts focusing on developmental toxicity. Materials and methods: Ames test, estrogen receptor alpha (ERα) assay, aryl hydrocarbon receptor (AhR) assay, embryonic stem cell test (EST), and zebrafish embryotoxicity test (ZET) were employed. Besides, a Derek Nexus toxicity prediction was performed on candidate structures obtained from metabolomics profiling of the extracts using liquid chromatography coupled to multistage mass spectroscopy (LC/MS n) and a MAGMa software based structural annotation. Results: Glucosinolates, which degrade to isothiocyanates, and biogenic amines were among the candidate molecules identified in the extracts by LC/MS n-MAGMa software structural annotation. Isothiocyanates and some other candidate molecules suggested a positive mutagenicity alert in Derek toxicity predictions. All the extracts showed negative mutagenicity in the Ames test. However, the Derek predictions also identified endocrine and developmental toxicity as possible endpoints of concern. This was further assessed using in vitro tests. Results obtained reveal that leaf extract shows AhR and ERα agonist activities, inhibited differentiation of ES-D3 stem cells into contracting cardiomyocytes in the EST (p<0.001) as well as inhibited hatching (p<0.01) and showed acute toxicity (p<0.01) in the ZET. Also, the fruit extract showed toxicity (p<0.05) towards zebrafish embryos and both 2 fruit and seed extracts showed AhR agonist activities while root extract was devoid of activity in all in vitro assays. Conclusion: The leaf extract tests positive in in vitro tests that this may point towards a developmental toxicity hazard. The current evaluations did not raise concerns of genotoxicity or developmental toxicity for the fruit, seed and root extracts. This is important given the use of especially these parts of M. subcordata, in traditional medicine and/or as (famine) food.

O Pentáculo Do Bem Estar Como Instrumento De Avaliação Do Modo De Vida Na Atenção Primária a Saúde

“…A triagem de potenciais candidatos a terapias alternativas (utilizando produtos naturais) e/ou medicamentos, são realizadas desde os primórdios da pesquisa clínica, através de modelos experimentais, especialmente, de roedores (ratos e camundongos), Majoritariamente, pode-se observar que a principal utilização do modelo Zebrafish tem sido para avaliar toxicidade de novos compostos ou produtos naturais candidatos para aceitação regulatória (MOURA et al, 2019;SARASQUETE et al, 2018;HALLARE et al, 2014;GEBRELIBANOS et al, 2019;ALMEIDA et al, 2020;VECIANA et al, 2014;SAID et al, 2020;XIA et al, 2020;VEEREN et al, 2020;TEIXEIRA et al, 2020;CHANDRAMOHAN et al, 2019). Testes de toxicidade remetem ao estudo da capacidade de uma substância em causar danos aos organismos vivos, geralmente associada a concentração e duração da exposição, que envolve uma cascata de eventos relacionados a mecanismos de interação com órgãos-alvo, projetando efeitos nocivos que se manifestam se o xenobiótico atingir concentrações suficientes para desencadear algum efeito tóxico (MOURA et al;CHANDRAMOHAN et al, 2019;VEEREN et al, 2020).…”

Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants

“…In developmental toxicity studies, the mortality of zebrafish embryos occurs before 24 hpf or just after hatching, and cardiac deformities are sometimes detected, such as pericardial edema, abnormal heart form due to edema or aplasia, and irregular heartbeat [ 4 ]. The motility of the zebrafish embryo can also be affected by toxins, as exhibited by coagulation, heart failure, and non-development of the yolk embryo’s tail [ 112 ].…”

“…Although many people view most medicinal plants as safe, poisoning can occur in some cases. Consumers can also be exposed to potential health risks caused by specific components or contaminants of botanical products; thus, their risk needs to be evaluated [ 4 , 5 ]. Plant materials and their extracts contain various toxic substances synthesized by plants as a defense against disease, insects, and other organisms [ 6 ].…”

“…Plant materials and their extracts contain various toxic substances synthesized by plants as a defense against disease, insects, and other organisms [ 6 ]. Botanical toxicity studies are complicated due to expense, time, use of animals, and the complex mix of components [ 4 , 7 ]. The most commonly used extraction solvents, from polar to non-polar, are water, ethanol, methanol, acetone, ethyl acetate, chloroform, dichloromethane and hexane, and numerous researchers have studied the effectiveness of these solvents [ 8 ].…”

Use of new approach methodologies to study the developmental toxicity of polycyclic aromatic hydrocarbons

“…The zebrafish genes share orthologs with around 70% of human genes, and many essential biological pathways are conserved across zebrafish and human . These advantages make zebrafish a good tool for screening the developmental hazard of chemicals Gebrelibanos Hiben et al, 2019;. However, for human risk assessment, whether the ZET can be used as a valid alternative remains controversial.…”