Ecdysteroids from the Korean Endemic Species Ajuga spectabilis with Activities against Glucocorticoid Receptors and 11β-Hydroxysteroid Dehydrogenase Type 1

Abstract

Two new ecdysteroids, spectasterone A (1) and spectasteroneB (2), together with four known ecdysteroids, breviflorasterone(3), ajugalactone (4), 20-hydroxyecdysone(5), and polypodine B (6) were isolatedfrom the Korean endemic plant Ajuga spectabilis using feature-based molecular networking analysis. The chemicalstructures of 1 and 2 were determined basedon the interpretation of NMR and mass spectrometric data. Their absoluteconfigurations were established using (3) J (H, H) coupling constants, NOESY interactions, Mosher'smethod, and ECD and DP4+ calculations. To identify their biologicaltarget, a machine learning-based prediction system was applied, andthe results indicated that ecdysteroids may have 11 & beta;-hydroxysteroiddehydrogenase type 1 (11 & beta;-HSD1)-related activity, which wasfurther supported by molecular docking results of ecdysteroids with11 & beta;-HSD1. Following this result, all the isolated ecdysteroidswere tested for their ability to affect the expression of 11 & beta;-hydroxysteroiddehydrogenase type 1 and glucocorticoid receptors (GRs) in HaCaT cellsirradiated with UVB. Compounds 2-5 exhibited inhibition of 11 & beta;-HSD1 expression and increasesin GR activity.