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

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 ; log P  - 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 ; log P  - 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 ; log P  - 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.