Identification of potential inhibitors against Alzheimer-related proteins in Cordyceps militaris ethanol extract: experimental evidence and computational analyses

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 mu g 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 beta-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) over bar - 13.6 kcal mol(-1)), polarized compatibility (polarizability 25.8 angstrom(3); 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).

Automated summary

Laboratory experiments were conducted to identify the chemical composition of Cordyceps militaris and provide evidence of its potential effects on Alzheimer's disease. Analysis revealed 21 bioactive compounds, with cordycepin content quantified at 0.32%. Bioassays demonstrated the extract's anti-Alzheimer potential. Computational predictions highlighted specific compounds as effective inhibitors and brain-penetrating agents.