RESUMEN
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 (IC50 = 6.443 ± 0.364 mg.mL-1) and α-glucosidase (IC50 = 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 Å3; logP - 1.30), 10 (ground state: -688.52406 a.u.; dipole moment 5.487 Debye; DS¯ -12.6 kcal.mol-1; polarizability 24.9 Å3; 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 Å3; 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.
RESUMEN
Laboratory experiments were carried out to identify the chemical composition of Cordyceps militaris and reveal the first evidence of their Alzheimer-related potential. Liquid chromatography-mass spectrometry analysis identified 21 bioactive compounds in the ethanol extract (1-21). High-performance liquid chromatography quantified the content of cordycepin (0.32%). Bioassays revealed the overall anti-Alzheimer potential of the extract against acetylcholinesterase (IC50 = 115.9 ± 11.16 µg mL-1). Multi-platform computations were utilized to predict the biological inhibitory effects of its phytochemical components against Alzheimer-related protein structures: acetylcholinesterase (PDB-4EY7) and ß-amyloid protein (PDB-2LMN). In particular, 7 is considered as a most effective inhibitor predicted by its chemical stability in dipole-based environments (ground state - 467.26302 a.u.; dipole moment 11.598 Debye), inhibitory effectiveness (DS¯ - 13.6 kcal mol-1), polarized compatibility (polarizability 25.8 Å3; logP - 1.01), and brain penetrability (logBB - 0.244; logPS - 3.047). Besides, 3 is promising as a brain-penetrating agent (logBB - 0.257; logPS - 2.400). The results preliminarily suggest further experimental attempts to verify the pro-cognitive effects of l(-)-carnitine (7). Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03714-9.