Glycation and α-glucosidase inhibitors from boesenbergia rotunda and lansium parasiticum

Abstract

Glycation is spontaneous non-enzymatic reaction between protein and glycation precursors; methylglyoxal (MG) that initially yields advanced glycation end-products (AGEs), which ultimately trigger to several severe complications. Therefore, the inhibition of AGEs formation is the imperative approach for alleviating diabetic complications. Moreover, one of typical diabetic therapy is α-glucosidase inhibition to reduce glucose level in bloodstream. Therefore, this research aims to study bioactivity and mechanism of natural products to inhibit glycation and α-glucosidase. From preliminary study of some phenolic compounds, flavanones from fingerroot (Boesenbergia rotunda) could inhibit glycation. The dichloromethane extract of fingerroot afforded three flavanones (pinocembrin, pinostrobin, and alpinetin), two chalcones (cardamomin and boesenbergin B), two dihydrochalcones (panduratin A and isopanduratin A), and one kavalactone (demethoxyyangonin). Most of isolated compounds showed higher AGEs formation inhibition than aminoguanidine (AG). Subsequent evaluation in MG-trapping assay indicated that their trapping potency was relatively comparable to AG. Their structure-activity relationships (SAR) of MG-trapping activity were investigated using the comparison of the structures of flavonoids. In addition, this is the first time that pinocembrin was tested ⍺-glucosidase inhibitory activity. In this study, we found a promising α-glucosidase inhibition (IC50 2.5-4.3 mg/mL) in the extract of Lansium parasiticum (syn L. domesticum; Meliaceae) fruit peels, which is a popular fruit in South-east Asia. It has been recognized as an important source of diverse triterpenoids, particularly a rare and unique skeleton of onoceranoids. A novel onoceranoid triterpene, named lamesticumin G along with four known compounds (lansionic acid, 3β-hydroxyonocera-8(26),14-dien-21-one, methyl lansiolate and lansiolic acid) were isolated from the ethyl acetate extract of the fruit peels of Lansium parasiticum. The structure of lamesticumin G was fully characterized using spectroscopic data. Lamesticumin G inhibited α-glucosidase (maltase) with IC50 value of 2.27 mM, while other compounds showed no inhibition.