Nine biflavonoids (1-9) were isolated from ethanolic extract of Selaginella uncinata (Desv.) Spring. Their structures were determined by spectra analysis. Compounds 1-9 were classified into four types according to the connection styles of the two flavonoid parts. Among them, 1 was elucidated as a new compound, while 4 was one with a new configuration. All isolates exhibited inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) in an enzyme assay with IC values ranging from 4.6 to 16.1 μM, and the relationship between the structures and activities was discussed. Docking simulations of these compounds demonstrated they had tight binding capacities towards the allosteric site of PTP1B. Additionally, the glucose uptake activities of 1-9 were evaluated in insulin-resistant HepG2 cells, while the effect of 1 on the activation of IRS-1/PI3K/Akt pathway was revealed by Western Blot analysis.
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