In silico studies of Ruellia tuberosa L. compounds as aldose reductase, dipeptidyl peptidase 4, and α-glucosidase inhibitors against type 2 diabetes mellitus

Abstract

Context: The search for a safe and effective anti-diabetic medication has escalated due to the unfavorable side effects of synthetic drugs and the geometric rise in diabetes mellitus cases. Ruellia tuberosa is an important medicinal plant that can potentially reduce postprandial hyperglycemia. Aims: To identify the inhibition of aldose reductase, dipeptidyl peptidase 4 (DPP-4), and α-glucosidase for anti-diabetic drug discovery from Ruellia tuberosa bioactive compounds using computational methods, including molecular docking, binding free energy estimates and ADMET predictions. Methods: A molecular docking study of betulin, betulinic acid, cirsiliol, cirsimarin, cirsimaritin, and pedalitin with aldose reductase, DPP-4, and α-glucosidase inhibitors was done using Glide XP-docking module. The adsorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was carried out by the QikProp module, and ligand binding energy was ascertained by the prime molecular mechanics with generalized born and surface area (MM/GBSA) module, Schrodinger suite 2020-2. Results: The molecular docking and complexes' MM/GBSA show specific interactions and high binding free energies. The ADMET prediction demonstrates the excellent safety profile, pharmacokinetic characteristics, and favorable drug-likeness of betulin, betulinic acid, cirsiliol, cirsimarin, cirsimaritin, and pedalitin. This study shows the inhibition potential of Ruellia tuberosa compounds against aldose reductase, DPP-4, and α-glucosidase inhibitors. Conclusions: Therefore, for this chemical to be developed further into novel pharmaceuticals for treating type 2 diabetes mellitus, optimization and experimental research are required.

Keywords

• anti-diabetic
• in silico admet
• mm/gbsa
• molecular docking
• ruellia tuberosa