Technological innovation has helped the zebrafish embryo gain ground as a disease model and an assay system for drug screening. Here, we review the use of zebrafish embryos and early larvae in... Show moreTechnological innovation has helped the zebrafish embryo gain ground as a disease model and an assay system for drug screening. Here, we review the use of zebrafish embryos and early larvae in applied biomedical research, using selected cases. We look at the use of zebrafish embryos as disease models, taking fetal alcohol syndrome and tuberculosis as examples. We discuss advances in imaging, in culture techniques (including microfluidics), and in drug delivery (including new techniques for the robotic injection of compounds into the egg). The use of zebrafish embryos in early stages of drug safety-screening is discussed. So too are the new behavioral assays that are being adapted from rodent research for use in zebrafish embryos, and which may become relevant in validating the effects of neuroactive compounds such as anxiolytics and antidepressants. Readouts, such as morphological screening and cardiac function, are examined. There are several drawbacks in the zebrafish model. One is its very rapid development, which means that screening with zebrafish is analogous to __screening on a run-away train.__ Therefore, we argue that zebrafish embryos need to be precisely staged when used in acute assays, so as to ensure a consistent window of developmental exposure. We believe that zebrafish embryo screens can be used in the pre-regulatory phases of drug development, although more validation studies are needed to overcome industry scepticism. Finally, the zebrafish poses no challenge to the position of rodent models: it is complementary to them, especially in early stages of drug research. Show less
Despite the rich diversity in molecular structures and biological functionality, the complex matrix of the compounds with a broad dynamic range has limited the use of plants as an important source... Show moreDespite the rich diversity in molecular structures and biological functionality, the complex matrix of the compounds with a broad dynamic range has limited the use of plants as an important source for drug development. Adressing this issue, several papers have described the use of the more holistic approach targeting on a wide range of metabolite present in plant extract, i.e. metabolomics. This new approach involves the use of various analytical methods followed by appropriate multivariate data analysis. The aim is to shorten the bioassay guided isolation route, particularly in the identification and dereplication step This thesis describes a new strategy to improve dereplication and identification steps in drug discovery process from plants. The integration of comprehensive extraction coupled to NMR metabolomics and multivariate data analysis is found to be a potential new approach to uncovering bioactive compounds from crude plant extracts. Show less