A New Fungal Triterpene from the Fungus Aspergillus flavus Stimulates Glucose Uptake without Fat Accumulation

Abstract

Through activity-guided fractionation, a new triterpene (asperflagin, 1) was isolated as a PPAR-γ agonist from the jellyfish-derived fungus Aspergillus flavus. Asperflagin displayed selective and moderate transactivation effects on PPAR-γ in Ac2F rat liver cells. Based on further biological evaluation and molecular docking analysis, we postulated that asperflagin might function as a PPAR-γ partial agonist. This compound was calculated to display a typical PPAR-γ ligand–receptor interaction that is distinct from that of full agonistic antidiabetics such as rosiglitazone, and may retain the antidiabetic effect without accompanying weight gain. Weight gain and obesity are typical side effects of the PPAR-γ full agonist rosiglitazone, and lead to suboptimal outcomes in diabetic patients. Compared to rosiglitazone, asperflagin showed higher glucose uptake in HepG2 human liver cells at concentrations of 20 and 40 μM but induced markedly lower adipogenesis and lipid accumulation in 3T3-L1 preadipocytes. These results suggest that asperflagin may be utilized for further study on advanced antidiabetic leads.

Marine natural products

“…136 Cytochalasins 308 and 309 were isolated from a culture of A. flavipes , although the possibility that they may be artefacts of isolation could not be excluded 137 and A. flavus strains yielded triterpene 310 (ref. 138) and α-cyclopiazonic acid alkaloid 311 . 139 …”

Peroxisome Proliferator Activated Receptor‐γ Agonistic Compounds from the Jellyfish‐Derived Fungus Cladosporium oxysporum

“…Additional references cited within the Supporting Information. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]…”

“…Supporting Information for this article is available on the WWW under https://doi.org/10.1002/MS-number. Additional references cited within the Supporting Information [35–50] …”