α‐Bisabolol, a Dietary Bioactive Phytochemical Attenuates Dopaminergic Neurodegeneration through Modulation of Oxidative Stress, Neuroinflammation and Apoptosis in Rotenone‐ Induced Rat Model of Parkinson’s disease

Hayate Javed, M. F.Nagoor Meeran, Sheikh Azimullah, Lujain Bader Eddin, Vivek Dhar Dwivedi, Niraj Kumar Jha, Shreesh Ojha

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Rotenone (ROT), a plant‐derived pesticide is a well‐known environmental neurotoxin associated with causation of Parkinson’s disease (PD). ROT impairs mitochondrial dysfunction being mitochondrial complex‐I (MC‐1) inhibitor and perturbs antioxidant‐oxidant balance that contributes to the onset and development of neuroinflammation and neurodegeneration in PD. Due to the scarcity of agents to prevent the disease or to cure or halt the progression of symptoms of PD, the focus is on exploring agents from naturally occurring dietary phytochemicals. Among numerous phytochemicals, α‐Bisabolol (BSB), natural monocyclic sesquiterpene alcohol found in many ornamental flowers and edible plants garnered attention due to its potent pharmacological properties and therapeutic potential. Therefore, the present study investigated the neuroprotective effects of BSB in a rat model of ROT‐induced dopaminergic neurodegeneration, a pathogenic feature of PD and underlying mechanism targeting oxidative stress, inflammation and apoptosis. BSB treatment significantly prevented ROT‐induced loss of dopaminergic neurons and fibers in the substantia nigra and striatum respectively. BSB treatment also attenuated ROT‐induced oxidative stress evidenced by inhibition of MDA formation and GSH depletion as well as improvement in antioxidant enzymes, SOD and catalase. BSB treatment also attenuated ROT‐induced activation of the glial cells as well as the induction and release of proinflammatory cytokines (IL‐1β, IL‐6 and TNF‐α) and inflammatory mediators (iNOS and COX‐2) in the striatum. In addition to countering oxidative stress and inflammation, BSB also attenuated apoptosis of dopaminergic neurons by attenuating downregulation of anti‐apoptotic protein Bcl‐2 and upregulation of pro‐apoptotic proteins Bax, cleaved caspases‐3 and 9. Further, BSB was observed to attenuate mitochondrial dysfunction by inhibiting mitochondrial lipid peroxidation, cytochrome‐C release and reinstates the levels/activity of ATP and MC‐I. The findings of the study demonstrate that BSB treatment salvaged dopaminergic neurons, attenuated microglia and astrocyte activation, induction of inflammatory mediators, proinflammatory cytokines and reduced the expression of pro‐apoptotic markers. The in vitro study on ABTS radical revealed the antioxidant potential of BSB. The results of the present.

Original languageEnglish
Article number1421
Pages (from-to)1-22
Number of pages22
JournalBiomolecules
Volume10
Issue number10
DOIs
Publication statusPublished - Oct 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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