Study On The Anti-angiogenesis Activity Of Eleven Natural Products Based On The Zebrafish Model

Zebrafish(Danio rerio)has been increasingly considered as an important vertebrate model for its high productivity,short period of production,capability of external fertilization,transparent embryo,high homology(87%)with human genome,as well as the similarity in signaling pathways and physiological structures and functions with mamalian animals.Zebrafish has been not only used in developmental and genetic biology studies but also in the evaluation of drug toxicity and safety,disease modeling and drug screening.As drug toxicity and clinical safety are main causes of drug failure in drug development,zebrafish has been proved as an ideal animal model for evaluation of drug toxicity and safety.We chose the zebrafish model to observe the acute toxicity of gleditsiosides from Fructus Gleditsiae Abnormalis and their structure-toxicity relationship.Results of our study demonstrated that the monoterpene unit and galactose unit can significantly enhance the toxicity of these compounds.The antiangiogenesis activity of saponins hasn't be detected during this study.Meanwhile,zebrafish models could reflect the drug toxicity on entire organisms in a more reasonable way.Taken together,zebrafish model is suitable to the early evaluation of drug toxicity.Quantities of studies have showed that there is a close correlation of angiogenesis with the growth and transfer of tumors as angiogenesis plays an important role in the physiological and pathological processes.Therefore the study of targeting angiogenesis has been paid more attention in antineoplastic therapies.Alpinia oxyphylla Miq.are characterized with the activities of neurological protection,improvement of learning and memory,ability in antioxidant,anti-aging,anti-tumor anti-inflammatory and anti-allergic.Two diarylheptanoids,Yakuchinone A and B,were isolated from Alpinia oxyphylla Miq.The activity and toxicity of these two compounds,together with a similar chemical curcumin,were conpared using transgenic zebrafish as in vivo model and human umbilical vein endothelial cell(HUVEC)as in vitro model.Anti-angiogenic index(AI)was used as the ratio between LC50 and EC50.The results suggested that in both in vitro and in vivo assays,curcumin exerted the most potent anti-angiogenic effect but with lowest toxicity among these compounds;Yakuchinone A was the second potent;Yakuchinone B has the lowest activity but with the highest toxicity in all three compounds.It can be concluded from our studies that both metabolism and toxicity of drug could be considered in zebrafish models during drug screening.Thus zebrafish model is an ideal choice for the drug activity screening.