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.
Highlights
Owing to their remarkable scaffold diversity, structures of natural products contribute to the discovery of potent leads for drug development [1]
Natural products isolated from marine microorganisms, green algae, sponges, or cnidarians [2] have always been attractive due to their remarkably high hit rates in biological evaluation [3]
Based on an investigation of the peroxisome proliferatoractivated receptor (PPAR) agonistic components from the jellyfish-derived fungus, A. flavus, a new triterpenoid 1 was identified as a potential PPARγ partial agonist
Summary
Owing to their remarkable scaffold diversity, structures of natural products contribute to the discovery of potent leads for drug development [1]. Natural products isolated from marine microorganisms, green algae, sponges, or cnidarians [2] have always been attractive due to their remarkably high hit rates in biological evaluation [3]. Compared to other marine organisms, microorganisms are more amenable to culture. According to the report of the International Diabetes Federation, worldwide diabetic patients will reach 642 million or more by 2040 [5]. Approximately 90% of diabetic patients have type 2 diabetes (T2DM), which is associated with hyperglycemia, glucose intolerance, and insulin resistance [5]. Peroxisome proliferatoractivated receptor (PPAR) ligands, such as fibric acid and thiazolidinediones (TZDs), have frequently been employed to combat T2DM or metabolic syndrome [6]
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