- Title
-
A New Hypoglycemic Prenylated Indole Alkaloid N-Oxide from Endophytic Fungus Pallidocercospora crystalline
- Authors
- Gao, S., Lin, X., Shi, Y., Zhou, H., Zheng, X., Li, M., Lin, T.
- Source
- Full text @ Int. J. Mol. Sci.
Indium-mediated reduction of N-O bonds. |
Structures of compounds 1–8. |
Key 1H-1H COSY, HMBC and key NOESY correlations for 1 and 2. |
Regression analysis of experimental versus calculated 13C NMR chemical shifts of 1 and 1′. |
Experimental and calculated ECD spectra of 1 and 2 in methanol. |
Compounds decreased the glucose level in a diabetic zebrafish model: (A) Schematic representation of zebrafish diabetic model Tg(−1.2ins:htBidTE-ON; LR). Zebrafish insulin promoter was employed to drive the proapoptotic gene human truncated Bid (htBid) under the control of a TRE-based system. After incubation with doxycycline (Dox) and tebufenozide (Tbf), the htBid will express and cause β-cell apoptosis. The htBid will not express without incubation of Dox and Tbf (red cross). (B) Representative confocal images of the β-cell number from Tg(−1.2ins:htBidTE-ON; LR); Tg(−1.2ins:H2BmCherry) larvae treated with (tBid + Dox + Tbf) or without (tBid) doxycycline and tebufenozide β cells were indicated by the fluorescence of mCherry. Scale bars indicate 10 μm. (C) Total free glucose level of 6 dpf Tg(−1.2ins:htBidTE-ON; LR) treated with or without compounds. Total of 10 μM of each compound was added at 5 dpf after the β-cell ablation, and lasted for 24 h; then, their glucose levels were measured. WT: wild type. RGZ: rosiglitazone, which was used as positive control. The values shown are means ± SEM from three independent experiments. ** p < 0.01, and *** p < 0.001 via one-way ANOVA. |
Compounds increased glucose uptake without any apparent toxicity: (A) The β-cell number of each compound-treated double transgenic zebrafish Tg(−1.2ins:htBidTE-ON; LR) Tg(−1.2ins:H2Bmcherry). Total of 10 μM of each compound was added at 5 dpf after the β-cell ablation for 24 h. (B) The glucose uptake indicated by 2-NBDG fluorescence. The larvae of each group were induced with doxycycline and tebufenozide except the group of tBid in 3 dpf for 48 h. Total of 10 μM of each compound was added at 5 dpf after the β-cell ablation for 24 h. Then, 2-NBDG was incubated for 3 h in dark. RGZ: rosiglitazone. The values shown are means ± SEM from three independent experiments. * p < 0.05, ** p < 0.01 and *** p < 0.001 via one-way ANOVA. (C) Morphology of 24 hpf embryos or 72 hpf zebrafish larvae treated with compounds. (D) Blood vessel morphology of 6 dpf zebrafish larvae Tg(flil:eGFP) treated with compounds. |