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

Nguyen Minh Thai; Ton That Huu Dat; Nguyen Thi Thanh Hai; Thanh Q Bui; Nguyen Vinh Phu; Phan Tu Quy; Nguyen Thanh Triet; Duy Toan Pham; Van De Tran; Nguyen Thi Ai Nhung

doi:10.1007/s13205-023-03714-9

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

3 Biotech. 2023 Sep;13(9):292. doi: 10.1007/s13205-023-03714-9. Epub 2023 Aug 4.

Authors

Affiliations

¹ Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, 700000 Vietnam.
² Mientrung Institute for Scientific Research, Vietnam National Museum of Nature, Vietnam Academy of Science and Technology (VAST), Hue, 530000 Vietnam.
³ Department of Chemistry, University of Sciences, Hue University, Hue, 530000 Vietnam.
⁴ Faculty of Basic Sciences, University of Medicine and Pharmacy, Hue University, Hue, 530000 Vietnam.
⁵ Tay Nguyen University, Buon Ma Thuot, Dak Lak 630000 Vietnam.
⁶ Faculty of Traditional Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, 70000 Vietnam.
⁷ Department of Chemistry, College of Natural Sciences, Can Tho University, Campus II, 3/2 Street, Can Tho, 900000 Vietnam.
⁸ Department of Health Organization and Management, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu, Can Tho, 900000 Vietnam.

PMID: 37547918
PMCID: PMC10403485 (available on 2024-09-01)
DOI: 10.1007/s13205-023-03714-9

Abstract

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 β-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 ( $\bar{DS}$ - 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.

Keywords: ADMET; Anti-Alzheimer; Cordyceps militaris; Density functional theory; Molecular docking simulation; QSARIS.

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