Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review.

Chanika D. Jayasinghe,Uthpala A. Jayawardena

doi:10.1155/2019/7272808

Abstract

Herbal remedies have been practiced by humans over centuries and therefore possess time-proven safety. However, it is imperative to evaluate the toxic effects of herbal medicine to confirm their safety, particularly when developing therapeutic leads. Use of laboratory animals such as rats, mice, and rabbits was considered as gold standard in herbal toxicity assessments. However, in the last few decades, the ethical consideration of using higher vertebrates for toxicity testing has become more contentious. Thus, possible alternative models entailing lower vertebrates such as zebrafish were introduced. The zebrafish embryotoxicity model is at the forefront of toxicology assessment due to the transparent nature of embryos, low cost, short cycle, higher fecundity, and genetic redundancy to the humans. Recently, its application has been extended to herbal toxicology. The present review intends to provide a comprehensive assembly of studies that applied the zebrafish embryo model for the assessment of herbal toxicity. A systematic literature survey was carried out in popular scientific databases. The literature search identified a total of 1014 articles in PubMed = 12, Scopus SciVerse® = 623, and Google Scholar = 1000. After screening, 25 articles were included in this review, and they were categorized into three groups in which the zebrafish embryotoxicity assay has been applied to investigate the toxicity of (1) polyherbal formulae/medical prescription (2 full texts), (2) crude extracts (12 full texts), and (3) phytocompounds/isolated constituents (11 full texts). These studies have investigated the toxicity of 6 polyherbal formulae, 16 crude extracts, and more than 30 phytocompounds/isolated constituents using the zebrafish embryotoxicity model. Moreover, this model has explicated the teratogenic effects and specific organ toxicities such as the kidney, heart, and liver. Furthermore, in some studies, the molecular mechanisms underlying the toxicity of herbal medicine have been elucidated. This comprehensive collection of scientific data solidifies the zebrafish embryo model as an effective model system for studying toxicological effects of a broad spectrum of herbal remedies. Henceforth, it provides a novel insight into the toxicity assessment of herbal medicine.

Highlights

Herbal medicine, with cultural and traditional roots extended over the history of many countries of the developing world is still pertinent and customary
A systematic review of scientific evidence of the use of the zebrafish embryotoxicity model for toxicity assessment of herbal medicine was undertaken in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) [18, 19]
A comprehensive search of the literature was conducted in the following databases: PubMed (US National Library of Medicine, USA), SciVerse Scopus (Elsevier Properties SA, USA), and Google Scholar for studies published before 31 March 2019. e following medical subject headings and keywords, “Zebrafish embryo herbal medicine,” “Zebrafish herbal toxicity,” “Zebrafish embryo/larval herbal plant toxicity,” “Zebrafish embryo/larval toxicity medicinal plants,” were included in the search

Summary

Introduction

With cultural and traditional roots extended over the history of many countries of the developing world is still pertinent and customary. The zebrafish embryotoxicity model has received considerable attention in toxicity assessment of natural products and herbal medicine. E transparent nature of embryos allows evaluating the effects of compounds on various organs, including the heart, brain, intestine, pancreas, cartilage, liver, and kidney without complicated processing [16] This model is more suitable for detecting the off-target effects or multiple targets due to the holistic action of natural products [17]. E scientific evidence gathered will be encouraged to apply the zebrafish embryotoxicity for herbal drug toxicity analysis This model will allow understanding the molecular mechanism underlying the toxicity of the natural products. It is anticipated that this work will highlight a novel vista in herbal toxicology that uses zebrafish embryotoxicity assay as an alternative for higher vertebrates

Materials and Methods

References compared with other assays

Curcuma longa Turmeric