Staprexanthones, Xanthone-Type Stimulators of Pancreatic β-Cell Proliferation from a Mangrove Endophytic Fungus

作者：Qi Gan, Chun-Yu Lin, Changjun Lu, Yimin Chang, Qian Che, Guojian Zhang, Tianjiao Zhu, Qianqun Gu, Zhiqiang Wu, Mingyu Li, Dehai Li · 发表于：Journal of Natural Products · 年份：2020 · DOI：10.1021/acs.jnatprod.0c00535 · 被引用次数：20 · 研究领域：Pancreatic function and diabetes、Plant tissue culture and regeneration

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.