FIGURE SUMMARY
Title

Brasilterpenes A-E, Bergamotane Sesquiterpenoid Derivatives with Hypoglycemic Activity from the Deep Sea-Derived Fungus Paraconiothyrium brasiliense HDN15-135

Authors
Wang, W., Shi, Y., Liu, Y., Zhang, Y., Wu, J., Zhang, G., Che, Q., Zhu, T., Li, M., Li, D.
Source
Full text @ Mar. Drugs
Fig. 1

Structures of compounds 1–5.
Fig. 2

Key HMBC and COSY correlations of compounds 1–5.
Fig. 3

Key NOESY correlations of compounds 1–5.

Fig. 4

Calculated ECD spectra of compounds 1–5 and the experimental ECD curves: (A) ECD spectra of compounds 1 and 2. (B) ECD spectra of compounds 3 and 4. (C) ECD spectra of compound 5.

Fig. 5

ORTEP drawing for the crystal structure of 1 (30% probability ellipsoids).

Fig. 6

Compounds 1 and 3 had hypoglycemic activity and low toxic effect in zebrafish: (A) Schematic diagram of β-cell ablation of transgenic zebrafish Tg(-1.2ins:htBidTE−ON; LR). In the transgene, the proapoptotic gene human truncated Bid (htBid) is under the control of a TRE-based promoter that is activated by a TE-ON driven by the zebrafish insulin promoter. After incubation with doxycycline (Dox) and tebufenozide (Tbf), the htBid will express and cause β-cell apoptosis. (B) The total free glucose level of 6 dpf Tg(-1.2ins:htBidTE−ON; LR) was treated with 10 μM of different compounds. After induction of the β-cell ablation, 10 μM of each compound was incubated with these larvae individually for 24 h, then their glucose levels were measured. Teton−, without β-cell ablation. Teton+, β-cell ablation without compound incubation. Rosiglitazone (RGZ) was used as a positive control. The values shown are means ± SEM from three independent experiments. ** p < 0.01, and **** p < 0.0001 by one-way ANOVA. (C) Compounds 1 and 3 did not show any toxic effect in zebrafish up to 200 μM, and the concentration of each compound was indicated.
Fig. 7

Compounds 1 and 3 did not increase β-cell regeneration: (A) Representative confocal images of the β-cell number from Tg(-1.2ins:htBidTE−ON; LR); Tg(-1.2ins:H2BmCherry) larvae treated with or without 10 μM of compounds. Scale bar indicates 10 μm. (B) Quantification of β-cell number from the larvae treated with or without compounds. Teton−, without β-cell ablation. Teton+, β-cell ablation without compound incubation. Rosiglitazone (RGZ) was used as control. The values shown are means ± SEM from three independent experiments. * p < 0.05, and **** p < 0.0001 by one-way ANOVA.
Fig. 8

Compounds 1 and 3 improved insulin sensitivity and suppressed gluconeogenesis: (A) Western blot for phosphorylated Akt (p-Akt) and total Akt (t-Akt) in ablated Tg(-1.2ins:htBidTE−ON; LR) larvae treated with or without 10 μM of compounds. GAPDH was used as an internal control. (B–E) Quantitative RT-PCR analysis of the expression of key gluconeogenic genes insa (B), gcga (C), pck1 (D), and g6pc1a.2 (E). Expression of β-actin was used as an internal control for all real-time PCR experiments. Teton−, without β-cell ablation. Teton+, β-cell ablation without compound incubation. Rosiglitazone (RGZ) was used as a control compound. All the values shown are means ± SEM from three independent experiments. * p < 0.05, ** p < 0.01, and *** p < 0.001 by one-way ANOVA.
Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Mar. Drugs
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Please check the highlighted fields and try again.
Thank you for submitting comments. Your input has been emailed to ZFIN curators who may contact you if additional information is required.
Oops. Something went wrong. Please try again later.