Valencene derived from essential oils of Psidium guajava L. as multi-target neurodegenerative inhibitor: a computational study

Ram Lal Swagat Shrestha; Sujan Dhital; Nirmal Parajuli; Prabhat Neupane; Manila Poudel; Timila Shrestha; Samjhana Bharati; Binita Maharjan; Bishnu Prasad Marasini; Jhashanath Adhikari Subin

doi:10.1071/CH24117

RESEARCH ARTICLE (Open Access)

Previous Contents Vol 78(6)

Valencene derived from essential oils of Psidium guajava L. as multi-target neurodegenerative inhibitor: a computational study

Ram Lal Swagat Shrestha ^A , Sujan Dhital

^A , Nirmal Parajuli ^A , Prabhat Neupane ^A , Manila Poudel

^B , Timila Shrestha ^A , Samjhana Bharati ^A , Binita Maharjan ^A , Bishnu Prasad Marasini

^C ^* and Jhashanath Adhikari Subin ^D ^*

+ Author Affiliations

- Author Affiliations

^A Department of Chemistry, Amrit Campus, Tribhuvan University, Lainchaur, Kathmandu, 44600, Nepal.

^B Department of Biotechnology, National College, Tribhuvan University, Lainchour, Kathmandu, 44600, Nepal.

^C Nepal Health Research Council, Ministry of Health and Population, Ramshah Path, Kathmandu, 44600, Nepal.

^D Bioinformatics and Cheminformatics Division, Scientific Research and Training Nepal Pty Ltd, Bhaktapur, 44800, Nepal.

^* Correspondence to: bishnu.marasini@gmail.com, subinadhikari2018@gmail.com

Handling Editor: Amir Karton

Australian Journal of Chemistry 78, CH24117 https://doi.org/10.1071/CH24117

Submitted: 15 August 2024 Accepted: 4 May 2025 Published online: 16 June 2025

© 2025 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

The prevalence of neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s has been gradually increasing in recent times. These diseases could respectively be treated through the inhibition of acetylcholinesterase (AChE), monoamine oxidase B (MAO-B) and huntingtin (Htt) proteins. This study aims to identify the compounds present in the oil of Psidium guajava L. using GC-MS analysis and the potent neurodegenerative inhibitors through computational methods. The results revealed the presence of 42 different phytocompounds, and molecular docking calculations demonstrated the firm binding of valencene with the receptor proteins AChE, MAO-B and HTT, with respective binding affinities of −9.246, −9.794 and −9.541 kcal mol^–1, better than that of reference drugs. All three complexes, valencene–AChE, valencene–MAO-B and valencene–HTT demonstrated good geometrical stability, showing smooth RMSD curves and ligand RMSD of ~3.5, ~3.0 and ~6.0 Å respectively from 100-ns molecular dynamics simulation. The thermodynamic stability assessed through the MMPBSA method, in terms of binding free energy changes, revealed sustained spontaneity and feasibility of the adduct formations. The pharmacodynamics and pharmacokinetics predicted the drug-like properties of the hit candidate. Therefore, after validating the computational results through in vivo and in vitro experiments, valencene could be a potential remedy for neurological disorders.

Keywords: ADMET, essential oil, free energy changes, molecular docking, molecular dynamics, neurodegenerative disorders, Psidium guajava.

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