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ID: ALA4334489

Journal: J Nat Prod

Title: Asperpyridone A: An Unusual Pyridone Alkaloid Exerts Hypoglycemic Activity through the Insulin Signaling Pathway.

Authors: Qiao Y, Xu Q, Feng W, Tao L, Li XN, Liu J, Zhu H, Lu Y, Wang J, Qi C, Xue Y, Zhang Y.

Abstract: A pyridone alkaloid, asperpyridone A (1), which possesses an unusual pyrano[3,2-c]pyridine scaffold, was isolated from solid cultures of the endophytic fungus Aspergillus sp. TJ23. Its structure, including its absolute configuration, was determined using a combination of nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, quantum chemical calculations (electronic circular dichroism), and X-ray crystallography. In vitro bioassays demonstrated that asperpyridone A (1) could function as a potential hypoglycemic agent, which exhibited pronounced glucose uptake effect in liver HepG2 cells, under both normal and insulin-resistant conditions, with higher efficacy than metformin. The underlying mechanism of asperpyridone A was elucidated by analyzing the genes expressed, the Gene Ontology (GO) function enrichment, the protein interaction network, and real-time quantitative reverse transcription polymerase chain reaction, which suggested that asperpyridone A exhibits hypoglycemic activity by activating the insulin signaling pathway. Moreover, on the basis of the hypoglycemic potency, fibroblast growth factor 21 (FGF21) was determined to be a potential target for asperpyridone A.

CiteXplore: 31490677

DOI: 10.1021/acs.jnatprod.9b00188