Inhibitory activity of xanthoangelol isolated from Ashitaba (Angelica keiskei Koidzumi) towards a-glucosidase and dipeptidyl peptidase-IV: in silico and in vitro studies

In Indonesia, the sap of Angelica keiskei Koidzumi has been utilized traditionally as a blood-sugar reducer, nonetheless, its molecular mechanism still needs to be studied. This study aimed to isolate xanthoangelol (XA) from the yellow sap of A. keiskei planted in Mount Rinjani, Indonesia, and to investigate its mechanism by in silico and in vitro methods towards alpha-glucosidase and dipeptidyl peptidase-IV (DPP-IV). The dried yellow sap was macerated using ethanol, subjected to liquid-liquid extraction using a different polarity of solvents, further gradient-eluted with column chromatography. The isolated compound, formed as yellow crystals, melting point 114-114.4 C, lambda(max) 368 nm, m/z 393.20 [M + H](+), was confirmed as XA. Acarbose, an alpha-glucosidase inhibitor, and sitagliptin, a DPP-IV inhibitor, respectively, were employed as the reference drugs for both the in silico and in vitro studies. XA interacts with essential amino acid residues 232-237 in the N-terminal N-loop of alpha-glucosidase by forming a hydrogen bond with Ala234, a salt-bridge with Asp232, and 9 hydrophobic interactions (binding energy-7.81 kcal/mol; Ki = 1.99 mu M). These binding modes resemble those of acarbose. Moreover, XA forms hydrogen bonds with Glu205 and Glu206 in the subsite S2 and pi-pi interaction with Phe357 in the extensive subsite S2 of DPP-IV (binding energy-8.34 kcal/mol; Ki = 0.873 mu M), which are similar to those of sitagliptin. XA inhibits both alpha-glucosidase (IC50 XA = 14.45 mu M; IC50 acarbose = 207 mu M) and DPP-IV (IC50 XA = 10.49 mu M; IC50 sitagliptin = 0.87 mu M). Taken together, XA isolated from the yellow sap of A. keiskei Koidzumi might possess the potential to be further developed as an inhibitor of alpha-glucosidase and DPP-IV.

Automated summary

The yellow sap of Angelica keiskei Koidzumi, traditionally used in Indonesia as a blood sugar reducer, contains xanthoangelol (XA) which shows potential as an inhibitor of alpha-glucosidase and dipeptidyl peptidase-IV (DPP-IV) through in silico and in vitro studies.