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

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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 (\(\overline{\mathrm{DS} }\) − 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).

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The main data generated in this work is included in the manuscript and the supplementary information. The raw data can be shared upon request from the corresponding author.

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Acknowledgements

This research was partly supported by the Cooperative Research Programme between the Institute of Applied Research in Science and Technology, University of Sciences, Hue University and KeFa Science and Technology Co., Ltd. The authors also acknowledge the partial support of Hue Unversity under grant number DHH2022-01-198. The authors thank the partial support of Hue University under the Core Research Program, Grant No. NCM.DHH.2020.04.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, 700000, Vietnam

    Nguyen Minh Thai

  2. Mientrung Institute for Scientific Research, Vietnam National Museum of Nature, Vietnam Academy of Science and Technology (VAST), Hue, 530000, Vietnam

    Ton That Huu Dat

  3. Department of Chemistry, University of Sciences, Hue University, Hue, 530000, Vietnam

    Nguyen Thi Thanh Hai, Thanh Q. Bui & Nguyen Thi Ai Nhung

  4. Faculty of Basic Sciences, University of Medicine and Pharmacy, Hue University, Hue, 530000, Vietnam

    Nguyen Vinh Phu

  5. Tay Nguyen University, Buon Ma Thuot, Dak Lak, 630000, Vietnam

    Phan Tu Quy

  6. Faculty of Traditional Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, 70000, Vietnam

    Nguyen Thanh Triet

  7. Department of Chemistry, College of Natural Sciences, Can Tho University, Campus II, 3/2 Street, Can Tho, 900000, Vietnam

    Duy Toan Pham

  8. Department of Health Organization and Management, Can Tho University of Medicine and Pharmacy, 179 Nguyen Van Cu, Can Tho, 900000, Vietnam

    Van De Tran

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Thai, N.M., Dat, T.T.H., Hai, N.T.T. et al. Identification of potential inhibitors against Alzheimer-related proteins in Cordyceps militaris ethanol extract: experimental evidence and computational analyses. 3 Biotech 13, 292 (2023). https://doi.org/10.1007/s13205-023-03714-9

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