Inhibitory activities of <i>Aruncus dioicus</i> alkaloidal glycosides against protein tyrosine phosphatase 1B and <i>α</i>-glucosidase: A methodical theory-experiment investigation

Objective: Aruncus dioicus has been known by the scientific literature and folk experiences for its diverse biological activities, including anti-hyperglycemic effects. Methodology: The aerial parts of the plant collected from Quan Lan Island (Vietnam) were subjected to a methodical theory-experiment investigation for its chemical composition and biological potentials. Results: Firstly, experimental isolation and spectroscopic characterization identified the compositional compounds, ie sambunigrin (1), prunasin (2), uridine (3), and adenosine (4). Secondly, their elucidated structures were predicted with promising bio-chemo-pharmacological potentiality by different computational platforms, ie: docking simulation (docking scores &lt; 10 kcal.mol −1 ); quantum calculation (dipole moments &lt; 3 Debye); QSARIS model (satisfying Lipinski's rule of five); SwissADME model (satisfying Pires’ interpretations). Finally, the compounds (1-4) were under accumulative purification and in vitro tests against diabetes-related enzymes, ie: protein tyrosine phosphatase 1B (1 with lowest IC 50 value 0.39 ± 0.26 μM, 2 with no activity) and α-glucosidase (1 with lowest IC 50 value 44.89 ± 0.93 μM, 2 with no activity); also, the inhibitory kinetics based on Lineweaver-Burk and Dixon plot experiments revealed the competitive inhibition mode of 1 against PTP1B ( K i value 0.49 μM). Conclusions: Altogether, the results obtained suggest that A. dioicus and its bioactive compounds, especially sambunigrin (1), uridine (3), and adenosine (4), could be considered as a natural source for further research and development of anti-diabetic agents.