Introduction

• Zebrafish, Danio rerio is a small vertebrate model organism which possesses physiological complexity of mammalian animals but allows study of human disease as well as throughput drug screens. Thus, the context of this whole organism, allows for a more comprehensive analysis of the range of biological activities and toxicity simultaneously, of a chemical's or multiple chemical’s effects, compared with in vitro assay. The embryos and early larvae are optically transparent, allowing for the screens with a measurable phenotypic readout using imaging microscopy; therefore, drug effect(s) on multiple targets underlying pathway of a disease or a normal physiological process could be observed. It is very suitable to identification of off-target effects of holistic action of the chemicals and natural products. The zebrafish models are important for new drug discovery and development.

Objectives – Targeting various diseases

  Primary goal

• To identify the active angiogenic, neuroprotective and anti-osteoporotic constituents, in selected compounds & natural products, and their molecular mechanism of action.

  Secondary goal

• To establish a drug screening platform for several diseases including cardiovascular problem, cancer, neurodegeneration and osteoporosis and to develop several imaging based bioassays for screening the biological effects on live cell culture and zebrafish models. At initial phase of establishment, we focus on the systematic evaluation of

1. Angiogenic activities, such as vascular vessel formation, in zebrafish in vivo
2. Neuroprotective activities, such as apoptosis of dopaminergic neurons in zebrafish in vivo
3. Bone formation and mineralization activities, such as proliferation of bone forming cell, osteoblast, in zebrafish in vivo
4. General toxicity

  Third goal

• Bioavailability and distribution of bioactive constituents and their metabolites in zebrafish by mass spectrometry

• Action mechanism of biological response of the active component in zebrafish by transcriptomic and proteomics approaches

Zebrafish screen platforms