Fishing for Nature’s Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products

Figure 4

Activity guided fractionation of the inner shell of the Japanese chestnut tree, Castanea crenata, using the fluorescent probe 2-NBDG in zebrafish larvae. (a) The methanol fraction produced significant glucose uptake in zebrafish compared to the hexane or ethyl acetate fraction. The red line on the graph indicates the threshold for selecting a “hit” drug (i.e., 2-NBDG uptake value for the zebrafish eye should show a ≥100% increase compared to that of the untreated larvae). (b) The methanol fraction was purified to isolate eight compounds: UP2.2 (scopoletin 4), UP3.11.1 (maslinic acid), UP3.5.3 (fragransin), UP4.2.3 (4-ketopentanoic acid), UP5.2.1 (4-hydroxy-5-methoxycinnamic acid), UP3.2 (fraxidin), UP3.3 (6,7,8-trimethoxycoumarin), and UP5.2.3 (3,4,5-trimethoxycinnamic acid). These compounds were tested for glucose uptake in the zebrafish (10 μg/mL dose for 1 h) and compared with emodin (a known inducer of glucose uptake). Fraxidin and maslinic acid were identified as hit compounds for inducing glucose uptake (figure modified from [26]).