Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus
Qi Gan, Chun-Yu Lin, Changjun Lu, Yimin Chang, Qian Che, Guojian Zhang, Tianjiao Zhu, Qianqun Gu, Zhiqiang Wu, Mingyu Li, Dehai Li
Abstract
This project was focused on the discovery of novel compounds that promote endogenous β-cell regeneration. Screening of extracts identified the fungus Stachybotrys chartarum as a promising candidate. After fermentation and extraction of S. chartarum, we isolated five new prenylated xanthones, namely, staprexanthones A–E (1–5), with staprexanthone A (1) being the first natural xanthone bearing a rare 4,5-dimethyl-1,3-dioxolane moiety. Compounds 1, 2, and 5 significantly increased β-cell numbers in vivo in a zebrafish model. Further analysis revealed that 2 and 5 promoted β-cell mass expansion by increasing proliferation of existing β-cells though promotion of cell-cycle progression at the G1/S transition. These findings indicate that prenylated xanthones are potential new drug leads for antidiabetes therapy by stimulating β-cell regeneration.