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Molecular Simulation Studies of Alpha Pinene, an Alkene in Search for Oxidative Stress Targeted Therapeutic Paradigms for the Treatment of Parkinson’s Disease: A Computational Approach and Its In-Vitro Antioxidant Validation

[ Vol. 18 , Issue. 12 ]

Author(s):

Rajnish Srivastava*, Pratim Kumar Choudhury, Suresh Kumar Dev and Vaibhav Rathore   Pages 1117 - 1135 ( 19 )

Abstract:


Aim: The present study was expected to explore the molecular interaction of five oxidative stress (OS) associated target receptors with Alpha-Pinene and its antioxidant validation for the effective treatment of Parkinson’s disease (PD).

Background: Oxidative stress (OS) via multitudinous cascades is considered to be the leading attribute to dopaminergic cell degeneration in PD. Furthermore, it is also well-linked to other mechanisms involved in the neurodegeneration process, like dysfunction of mitochondria, neuroinflammation and excitotoxicity due to NO.

Objective: The present investigation was to establish a molecular association of OS-associated target receptors with the bioactive compound alpha-pinene and how this molecular interaction empowers the mitigation of PD.

Materials and Methods: Five different molecular targets namely Peroxisome Proliferator-Activated Receptor- Gamma (PPARγ), Liver-X receptor beta (LXR- β), Human Monoamine Oxidase-B (MAO-B), Human Nuclear receptor related-1 protein (Nurr1) and Human Lipoprotein-associated phospholipase A2 (Lp-PLA2) were obtained from RCSB-PDB, which has some leading association in the inhibition of the OS-induced neurodegeneration. Molecular interactions were stuffed by the simulation molecular docking software. Antioxidant activity was validated by in-vitro models as per standardized procedures against 2,2- diphenyl-1- picrylhydrazyl (DPPH), 2,2'-azinobis-(3- ethylbenzothiazoline -6-sulfonic acid) (ABTS), Ferric ion (Fe3+), Hydroxyl (•OH), nitric oxide (•NO), Peroxynitrite (ONOO-) and Hypochlorous acid (HOCl).

Result: Our results indicated that alpha-pinene can interact with all the five different target receptors at the active binding site. Alpha-pinene was found to show better interaction with MAO-B, Nurr1 and PPARγ with binding energy of -5.50, -4.52 and -5.25, respectively as compared to the native ligand. Furthermore, the interaction of alpha-pinene with LXR-β and Lp-PLA2 was also significant with binding energy of -5.6 and -5.12, respectively. It also capable of neutralizing all the different free radicals under consideration with significant IC50 values against HOCl and •NO.

Conclusion: It might be concluded that alpha-pinene could act as a potential inhibitor and scavenger of OS which could act on the multiple target receptors under consideration.

Keywords:

Molecular targets, parkinson’s disease, alpha pinene, in-vitro, antioxidant, molecular docking, ligand.

Affiliation:

Department of Pharmaceutical Science, Mohanlal Sukhadia University, Udaipur, Rajasthan, Department of Pharmaceutical Science, Mohanlal Sukhadia University, Udaipur, Rajasthan, Department of Pharmaceutical Science, Mohanlal Sukhadia University, Udaipur, Rajasthan, Department of Pharmaceutical Science, Mohanlal Sukhadia University, Udaipur, Rajasthan



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