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Glycyrrhizic acid Attenuates Neuroinflammation and Oxidative Stress in Rotenone Model of Parkinson’s Disease

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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.

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Abbreviations

ABC:

Avidin biotin complex

COX-2:

Cyclooxygenase-2

DAB:

Diamino benzidine

GA:

Glycyrrhizic acid

GFAP:

Glial fibrillary acidic protein

GSH:

Reduced glutathione

IBA-1:

Ionized calcium-binding adaptor molecule-1

iNOS:

Inducible nitric oxide synthase

MDA:

Malondialdehyde

PD:

Parkinson’s disease

ROT:

Rotenone

SOD:

Superoxide dismutase

TH:

Tyrosine hydroxylase

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Acknowledgments

The research grant support from the United Arab Emirates University and the National Research foundation, United Arab Emirates to MEH and SO are duly acknowledged. The authors would also like to acknowledge Mahmoud Hag Ali, Animal Research Facility controller for his help with animal care and welfare.

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    Authors and Affiliations

    1. Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box - 17666, Al Ain, United Arab Emirates

      Shreesh Ojha & Sheikh Azimullah

    2. Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, PO Box - 17666, Al Ain, United Arab Emirates

      Hayate Javed, Salema B. Abul Khair & M. Emdadul Haque

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    1. Shreesh Ojha
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    2. Hayate Javed
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    3. Sheikh Azimullah
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    5. M. Emdadul Haque
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    Correspondence to M. Emdadul Haque.

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    There are no patents, products in development, or marketed products to declare. This study was supported by grants from the College of Medicine & Health Sciences, UAE University, UAE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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    All procedures performed in studies involving animals were in accordance with the ethical standards of the Animal Research Ethics Committee, United Arab Emirates University, UAE.

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    Shreesh Ojha and Hayate Javed have contributed equally to this work.

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    Ojha, S., Javed, H., Azimullah, S. et al. Glycyrrhizic acid Attenuates Neuroinflammation and Oxidative Stress in Rotenone Model of Parkinson’s Disease. Neurotox Res 29, 275–287 (2016). https://doi.org/10.1007/s12640-015-9579-z

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