Evaluation of the inhibitory potentials of selected compounds from Costus spicatus (Jacq.) rhizome towards enzymes associated with insulin resistance in polycystic ovarian syndrome: an in silico study

Abstract

Abstract Background Polycystic ovary syndrome (PCOS) is a chronic endocrine disorder prevalent in premenopausal women and is characterized by a range of physiological and biochemical abnormalities which may include reproductive, endocrine, and metabolic alterations such as insulin resistance. Insulin resistance is the hallmark of PCOS as it predisposes the affected subjects to a higher risk of impaired glucose tolerance and type 2 diabetes mellitus (T2DM). In this study, the inhibitory activities of phytosterols and saccharides from aqueous extract of Costus spicatus rhizome were investigated against phosphoenolpyruvate carboxykinase (PEPCK), α-amylase, β-glucosidase, and fructose 1,6-biphosphatase (FBPase) in silico as potential novel therapeutic targets for T2DM-associated-PCOS. Phytochemical constituents of the plant were determined using gas chromatography-mass spectrophotometry (GC-MS), while molecular docking of the compounds with PEPCK, α-amylase, β-glucosidase, and FBPase was conducted using Vina. Thereafter, the binding modes were determined using Discovery Studio Visualizer, 2020. Results GCMS analysis of an aqueous extract of Costus spicatus rhizome revealed the presence of three compounds with a higher binding affinity for all enzymes studied compared to metformin. The compounds also interacted with key amino acid residues crucial to the enzyme’s activities. This study identified Lyxo-d-manno-nononic-1,4-lactone as potential multi-target inhibitors of PEPCK, α-amylase, β-glucosidase, and FBPase with reasonable pharmacokinetic properties and no significant toxicity. Conclusion These compounds can be explored as potential therapeutic agents for the management of insulin resistance in PCOS, subject to further experimental validation.

Keywords

• Polycystic ovary syndrome (PCOS)
• PEPCK
• α-amylase
• β-glucosidase
• FBPase
• GC-MS