Identification of potential anti-hyperglycemic compounds in Cordyceps militaris ethyl acetate extract: in vitro and in silico studies

• Published in: Journal of biomolecular structure & dynamics 2025-01, Vol.43 (2), p.627-643
• Main Authors: Bui, Thanh Q., Dat, Ton That Huu, Quy, Phan Tu, Hai, Nguyen Thi Thanh, Thai, Nguyen Minh, Phu, Nguyen Vinh, Tuan, Le Van, Huynh, Lam K., Li, Mai Suan, Nhung, Nguyen Thi Ai
• Format: Article
• Language: English
• Subjects: Acetates - chemistry; ADMET; alpha-Amylases - antagonists & inhibitors; alpha-Amylases - metabolism; alpha-Glucosidases - chemistry; alpha-Glucosidases - metabolism; antidiabetics; Computer Simulation; Cordyceps - chemistry; Cordyceps militaris; density functional theory; Glycoside Hydrolase Inhibitors - chemistry; Glycoside Hydrolase Inhibitors - pharmacology; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Molecular Docking Simulation; Molecular Dynamics Simulation; Plant Extracts - chemistry; Plant Extracts - pharmacology; QSARIS
• ISSN: 0739-1102; 1538-0254; 1538-0254
• DOI: 10.1080/07391102.2023.2283156

Cordyceps militaris has been long known for valuable health benefits by folk experience and was recently reported with diabetes-tackling evidences, thus deserving extending efforts on screening for component-activity relationship. In this study, experiments were carried out to find the evidence, justification, and input for computations on the potential against diabetes-related protein structures: PDB-4W93, PDB-3W37, and PDB-4A3A. Liquid chromatography identified 14 bioactive compounds in the ethyl acetate extract (1-14) and quantified the contents of cordycepin (0.11%) and adenosine (0.01%). Bioassays revealed the overall potential of the extract against α-amylase (IC 50 = 6.443 ± 0.364 mg.mL −1 ) and α-glucosidase (IC 50 = 2.580 ± 0.194 mg.mL −1 ). A combination of different computational platforms was used to select the most promising candidates for applications as anti-diabetic bio-inhibitors, i.e. 1 (ground state: −888.49715 a.u.; dipole moment 3.779 Debye; DS ¯ −12.3 kcal.mol −1 ; polarizability 34.7 Å 3 ; logP − 1.30), 10 (ground state: −688.52406 a.u.; dipole moment 5.487 Debye; DS ¯ −12.6 kcal.mol −1 ; polarizability 24.9 Å 3 ; logP − 3.39), and 12 (ground state: −1460.07276 a.u.; dipole moment 3.976 Debye; DS ¯ −12.5 kcal.mol −1 ; polarizability 52.4 Å 3 ; logP − 4.39). The results encourage further experimental tests on cordycepin (1), mannitol (10), and adenosylribose (12) to validate their in-practice diabetes-related activities, thus conducive to hypoglycemic applications. Communicated by Ramaswamy H. Sarma