本論文利用斑馬魚進行活體毒性及抗氧化能力測試，作為篩選黃酮衍生物防護UVB能力的平台。首先，以100 mJ/cm2的UVB照射三天大的斑馬魚幼魚，每半小時照射一次共六次，發現最易觀察鰭傷害的變化是腹鰭。再加入一系列黃酮衍生物預防UVB所造成的傷害，以生物存活統計分析其毒性，並以抗氧化能力測試比較其防護UVB的能力，發現morin跟chrysin具有良好防護UVB的效果。進一步藉由理論與實驗結合的藥物開發方法—定量結構活性關係（Quantitative Structure-Activity Relationship. QSAR）分析，分別建立黃酮衍生物的毒性模型及抗氧化性模型，驗證QSAR模型分析與斑馬魚活體實驗的結果相符，並推測出黃酮衍生物在3’與4’位置的取代基若為氨基則具有良好的抗氧化能力。本研究結果顯示，結合斑馬魚活體實驗與QSAR分析，可提供快速篩選及推測驗證新化合物毒性及防護UVB能力的平台。 To screen UV-protective flavonoid derivatives with higher efficacy and less toxicity, this study used zebrafish as a whole-organism platform to examine the toxicity and antioxidant activity of flavonoid derivatives. AT first, 3-dpf zebrafish were exposed to 100 mJ/cm2 of UVB given six times separated by 30 min intervals. Fin malformation phenotypes are the most evident consequences after exposure to UVB, pelvic fin seemed to be the most sensitive target after UVB exposure. The next, a series of flavonoid derivatives were next examined for their toxicity and antioxidant activity. “Morin” and “Chrysin” showed better UV-protective activities among these tested flavonoid derivatives. Furthermore, Quantitative Structure-Activity Relationship (QSAR) analysis was used to establish both toxicity and antioxidant activity models for flavonoid derivatives. The theoretical antioxidant activities predicted by QSAR models were consistent with the experimental data obtained from zebrafish. Using QSAR models to predict a series of flavonoid derivatives, our data suggested that the amino substituents at positions 3’ and 4’ of the A ring may play important roles in the antioxidant activity.
In conclusion, this study demonstrated that combining zebrafish and QSAR can provide a useful platform to quickly evaluate the toxicity and antioxidant activity of UV-protective compounds.