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Molecular docking and molecular dynamics approach to identify potential compounds in Huperzia squarrosa for treating Alzheimer’s disease

  • Bui Thanh Tung EMAIL logo , Ta Thi Thu Hang , Nguyen Bao Kim , Nguyen Hong Nhung , Vu Khanh Linh and Dang Kim Thu
Published/Copyright: May 30, 2022
Journal of Complementary and Integrative Medicine
From the journal Journal of Complementary and Integrative Medicine Volume 19 Issue 4

Abstract

Objectives

Alzheimer’s disease (AD) is a lingering progressive neurodegenerative disorder that causes patients to lose cognitive function. The enzyme Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Monoamine oxidase A (MAO A), Beta-secretase cleavage enzyme (BACE 1) and N-methyl-D-aspartate (NMDA) receptors play an important role in the pathogenesis of Alzheimer’s disease. Therefore, inhibiting enzymes is an effective method to treat Alzheimer disease. In this study, we evaluated in silico inhibitory effects of AChE, BuChE, MAO A, BACE 1 and NMDA enzyme of Huperzia squarrosa’s compounds

Methods

The three-dimensional (3D) of N-methyl-D-aspartate receptor (PDB ID: 1PBQ), enzyme β-secretase 1 (PDB ID: 4X7I), enzyme monoamine oxidase A (PDB ID: 2Z5X), enzyme butyrylcholinesterase (PDB ID: 4BDS) and enzyme acetylcholinesterase (PDB ID: 1EVE) were retrieved from the Protein Data Bank RCSB. Molecular docking was done by Autodock vina software and molecular dynamics (MD) simulation of the ligand-protein complex with the least binding energy pose was perfomed by MOE. Lipinski Rule of Five is used to compare compounds with drug-like and non-drug-like properties. Pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool.

Results

Based on previous publication of Huperzia squarrosa, we have collected 15 compounds. In these compounds, huperzine B, huperzinine, lycoposerramine U N-oxide, 12-epilycodine N-oxide showed strongly inhibit the five AChE, BuChE, MAO A, BACE 1 and NMDA targets for Alzheimer’s treatment. Lipinski rule of five and ADMET predict have shown that four above compounds have drug-likeness properties, good absorption ability and cross the blood-brain barrier, which have the most potential to become drugs for the treatment of Alzheimer’s in the future. Furthermore, MD study showed that huperzine B and huperzinine have stability of the docking pose with NMDA target.

Conclusions

In this study, we found two natural compounds in Huperzia squarrosa including Huperzine B and Huperzinine have drug-likeness properties, good absorption ability and cross the blood-brain barrier, which have potential to become drugs for the treatment of Alzheimer’s in the future.

Keywords: alzheimer; Huperzia squarrosa ; in silico ; molecular docking; molecular dynamics
Corresponding author: Bui Thanh Tung, Department of Pharmacology, University of Medicine and Pharmacy, Vietnam National University Hanoi, Office 506, Y1 Building, 144 Xuan Thuy, Cau Giay, Ha Noi, Vietnam, E-mail:

  1. Research funding: None declared.

  2. Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

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Received: 2021-10-07
Revised: 2022-04-21
Accepted: 2022-05-02
Published Online: 2022-05-30

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jcim-2021-0462
Keywords for this article
alzheimer; Huperzia squarrosa; in silico; molecular docking; molecular dynamics

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. A preliminary systematic review and meta-analysis on the effects of heart rate variability biofeedback on heart rate variability and respiration of athletes
  4. The potential positive epigenetic effects of various mind-body therapies (MBTs): a narrative review
  5. The effect of Chlorella vulgaris on obesity related metabolic disorders: a systematic review of randomized controlled trials
  6. Biological and medicinal application of Cucumis sativus Linn. – review of current status with future possibilities
  7. The effect of the herbal medicine on severity of cyclic mastalgia: a systematic review and meta-analysis
  8. Research Articles
  9. Chemical compositions, antibacterial, antifungal and cytotoxic effects of Alhagi mannifera five extracts
  10. Anticonvulsive and anti-epileptogenesis effects of Echinacea purpurea root extract, an involvement of CB2 receptor
  11. Fermented maize slurry (Ogi) and its supernatant (Omidun) mitigate elevated intraocular pressure by modulating BDNF expression and glial plasticity in the retina-gut axis of glaucomatous rats
  12. Levetiracetam exposure during prenatal and postnatal period induces cognitive decline in rat offsprings, not completely prevented by Bacopa monnieri
  13. Antibiofilm action of Persea americana glycolic extract over Acinetobacter baumannii and absence of toxicity in Galleria mellonella
  14. Validation of Unani concept of Abadāl-i-Adwiya (drug substitution) by physicochemical standardization and hepatoprotective activity of Aristolochia rotunda Linn. and its substitute Curcuma Zedoaria Rosc. in albino Wistar rats
  15. Cinnamon oil as a co-chemotherapy agent through inhibition of cell migration and MMP-9 expression on 4T1 cells
  16. Assessment of biochemical changes in normal and diabetic rats treated by phenolic enriched extracts of Juglans regia L. barks
  17. Influence of Clerodendrum volubile leaf extract on doxorubicin-induced toxicity and inhibition of carbonyl reductase mediated metabolism
  18. Quantification of anacardic acid, the toxic component in raw and purified samples of Semecarpus anacardium L. by Siddha purification processes
  19. Molecular docking and molecular dynamics approach to identify potential compounds in Huperzia squarrosa for treating Alzheimer’s disease
  20. Evaluation of ethanol extracts from three species of Artocarpus as natural gastroprotective agents: in vivo and histopathological studies
  21. Attenuation of cisplatin induced myelosuppression by methanol extract of Cedrus deodara in Wistar rats
  22. Acute and sub-acute toxicity assessment of the standardized extract of Sanguisorba minor in vivo
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