title: Neuroprotective effect of nerolidol against neuroinflammation and oxidative stress induced by rotenone.
abstract: Parkinson disease (PD) is a movement disorder affecting 1 % of people over the age of 60. The etiology of the disease is unknown; however, accumulating evidence suggests that mitochondrial defects, oxidative stress, and neuroinflammation play important roles in developing the disease. Current medications for PD can only improve its symptoms, but are unable to halt its progressive nature. Although many therapeutic approaches are available, new drugs are urgently needed for the treatment of PD. Thus, the present study was undertaken to investigate the neuroprotective potential of nerolidol, a sesquiterpene alcohol, on a rotenone-induced experimental model of PD, where male Wistar rats intraperitoneally received rotenone (ROT) at a dose of 2.5 mg/kg of body weight once daily for 4 weeks.
  
  
  
  Nerolidol, which has antioxidant and anti-inflammatory properties, was injected intraperitoneally at 50 mg/kg of body weight, once daily for 4 weeks, and at 30 min prior to ROT administration. ROT administration significantly reduced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the level of the antioxidant tripeptide glutathione (GSH). Moreover, ROT increased the levels of the lipid peroxidation product malondialdehyde (MDA), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), and inflammatory mediators (COX-2 and iNOS) in rat brain tissues. Immunostaining of brain tissue sections revealed a significant increase in the number of activated astrocytes (GFAP) and microglia (Iba-1), along with the concomitant loss of dopamine (DA) neurons in the substantia nigra pars compacta and dopaminergic nerve fibers in the striatum of ROT-treated rats. As expected, nerolidol supplementation to ROT-injected rats significantly increased the level of SOD, CAT, and GSH, and decreased the level of MDA. Nerolidol also inhibited the release of proinflammatory cytokines and inflammatory mediators. Finally, nerolidol treatment prevented ROT-induced glial cell activation and the loss of dopaminergic neurons and nerve fibers, and ultimately attenuated ROT-induced dopaminergic neurodegeneration.
  
  
  
  Our findings are the first to show that the neuroprotective effect of nerolidol is mediated through its anti-oxidant and anti-inflammatory activities, which strongly supports its therapeutic potential for the treatment of PD.
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE.
authors.forename: Hayate
authors.initials: H
authors.lastname: Javed
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE.
authors.forename: Sheikh
authors.initials: S
authors.lastname: Azimullah
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE.
authors.forename: Salema B
authors.initials: SB
authors.lastname: Abul Khair
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE. shreeshojha@uaeu.ac.ae.
authors.forename: Shreesh
authors.initials: S
authors.lastname: Ojha
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE. ehaque@uaeu.ac.ae.
authors.forename: M Emdadul
authors.initials: ME
authors.lastname: Haque
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D000978:Antiparkinson Agents / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D015394:Molecular Structure; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D012402:Rotenone; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; D012402:Rotenone; C037055:nerolidol
keywords: Nerolidol; Neurodegeneration; Oxidative stress; Parkinson disease; Rotenone