title: Glycyrrhizic acid Attenuates Neuroinflammation and Oxidative Stress in Rotenone Model of Parkinson's Disease.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting humans. It is characterized by dopaminergic neurodegeneration, mitochondrial impairment, and oxidative stress, enhanced lipid peroxidation, and induction of pro-inflammatory cytokines. We evaluated the neuroprotective efficacy of glycyrrhizic acid (GA), an active component of licorice, against rotenone-induced-oxidative stress and neuroinflammation in a PD rat model. Since PD is progressive and chronic, we investigated the effect of chronic administration of GA for 4 weeks (50 mg/kg/day), 30 min prior to rotenone administration. Rotenone administration significantly reduced the activity of superoxide dismutase and catalase, and caused the depletion of reduced glutathione. A concomitant increase in the levels of the lipid peroxidation product malondialdehyde was observed. It also significantly enhanced the levels of pro-inflammatory cytokines in the midbrain and elevated the levels of inflammatory mediators such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Immunohistochemical analysis revealed significant increments in ionized calcium-binding adaptor molecule-1 (Iba-1) levels, and in glial fibrillary acidic protein (GFAP) levels, and loss of dopamine neurons in the substantia nigra pars compacta upon rotenone challenge. GA treatment significantly attenuated the dopamine neuron loss and decreased the Iba-1 and GFAP activation induced by the rotenone insult. GA also improved antioxidant enzyme activity, prevented glutathione depletion, inhibited lipid peroxidation, and attenuated induction of pro-inflammatory cytokines. Subsequently, GA attenuated the increased levels of the inflammatory mediators COX-2 and iNOS. In conclusion, GA protects against rotenone-induced-PD. The neuroprotective effects of GA are attributed to its potent antioxidative and anti-inflammatory properties.
authors.affiliation: Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box - 17666, Al Ain, United Arab Emirates.
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, United Arab Emirates.
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, United Arab Emirates.
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, United Arab Emirates.
authors.forename: Salema B
authors.initials: SB
authors.lastname: Abul Khair
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, PO Box - 17666, Al Ain, United Arab Emirates. ehaque@uaeu.ac.ae.
authors.forename: M Emdadul
authors.initials: ME
authors.lastname: Haque
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019695:Glycyrrhizic Acid / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D008840:Microfilament Proteins; D012402:Rotenone; D019695:Glycyrrhizic Acid; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Glycyrrhizic acid; Inflammation; Neurodegeneration; Oxidative stress; Parkinson’s disease; Rotenone