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Neuroprotective potential of ferulic acid in the rotenone model of Parkinson's disease.
Drug Des Devel Ther. 2015; 9:5499-510.DD

Abstract

Parkinson's disease (PD) is a chronic, progressive, and the second most common form of neurodegenerative disorders. In order to explore novel agents for the treatment of PD, in the current study, we have evaluated the neuroprotective efficacy of ferulic acid (FA) using rotenone (ROT)-induced rat model of PD. ROT was administered 2.5 mg/kg body weight to male Wistar rats for 4 weeks to induce the PD. Since PD is progressive and chronic in nature, the paradigm for evaluating FA was based on chronic administration for 4 weeks at the dose of 50 mg/kg, 30 minutes prior to ROT administration. ROT administration caused significant reduction in endogenous antioxidants such as superoxide dismutase, catalase, and glutathione. ROT challenge-induced lipid peroxidation evidenced by increased malondialdehyde following perturbation of antioxidant defense. Apart from oxidative stress, ROT also activated proinflammatory cytokines and enhanced inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide synthase. The immunofluorescence analysis revealed a significant increase in the number of activated microglia and astrocytes accompanied by a significant loss of dopamine (DA) neurons in the substantia nigra pars compacta area upon ROT injection. However, treatment with FA rescued DA neurons in substantia nigra pars compacta area and nerve terminals in the striatum from the ROT insult. FA treatment also restored antioxidant enzymes, prevented depletion of glutathione, and inhibited lipid peroxidation. Following treatment with FA, the inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide synthase and proinflammatory cytokines were also reduced. Further, the results were supported by a remarkable reduction of Iba-1 and GFAP hyperactivity clearly suggests attenuation of microglial and astrocytic activation. Results of our study suggest that FA has promising neuroprotective effect against degenerative changes in PD, and the protective effects are mediated through its antioxidant and anti-inflammatory properties.

Authors+Show Affiliations

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE.Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE.Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE.Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE.Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26504373

Citation

Ojha, Shreesh, et al. "Neuroprotective Potential of Ferulic Acid in the Rotenone Model of Parkinson's Disease." Drug Design, Development and Therapy, vol. 9, 2015, pp. 5499-510.
Ojha S, Javed H, Azimullah S, et al. Neuroprotective potential of ferulic acid in the rotenone model of Parkinson's disease. Drug Des Devel Ther. 2015;9:5499-510.
Ojha, S., Javed, H., Azimullah, S., Abul Khair, S. B., & Haque, M. E. (2015). Neuroprotective potential of ferulic acid in the rotenone model of Parkinson's disease. Drug Design, Development and Therapy, 9, 5499-510. https://doi.org/10.2147/DDDT.S90616
Ojha S, et al. Neuroprotective Potential of Ferulic Acid in the Rotenone Model of Parkinson's Disease. Drug Des Devel Ther. 2015;9:5499-510. PubMed PMID: 26504373.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective potential of ferulic acid in the rotenone model of Parkinson's disease. AU - Ojha,Shreesh, AU - Javed,Hayate, AU - Azimullah,Sheikh, AU - Abul Khair,Salema B, AU - Haque,M Emdadul, Y1 - 2015/10/07/ PY - 2015/10/28/entrez PY - 2015/10/28/pubmed PY - 2016/7/7/medline KW - neurodegeneration KW - neuroinflammation KW - neurotoxicity KW - reactive oxygen species SP - 5499 EP - 510 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 9 N2 - Parkinson's disease (PD) is a chronic, progressive, and the second most common form of neurodegenerative disorders. In order to explore novel agents for the treatment of PD, in the current study, we have evaluated the neuroprotective efficacy of ferulic acid (FA) using rotenone (ROT)-induced rat model of PD. ROT was administered 2.5 mg/kg body weight to male Wistar rats for 4 weeks to induce the PD. Since PD is progressive and chronic in nature, the paradigm for evaluating FA was based on chronic administration for 4 weeks at the dose of 50 mg/kg, 30 minutes prior to ROT administration. ROT administration caused significant reduction in endogenous antioxidants such as superoxide dismutase, catalase, and glutathione. ROT challenge-induced lipid peroxidation evidenced by increased malondialdehyde following perturbation of antioxidant defense. Apart from oxidative stress, ROT also activated proinflammatory cytokines and enhanced inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide synthase. The immunofluorescence analysis revealed a significant increase in the number of activated microglia and astrocytes accompanied by a significant loss of dopamine (DA) neurons in the substantia nigra pars compacta area upon ROT injection. However, treatment with FA rescued DA neurons in substantia nigra pars compacta area and nerve terminals in the striatum from the ROT insult. FA treatment also restored antioxidant enzymes, prevented depletion of glutathione, and inhibited lipid peroxidation. Following treatment with FA, the inflammatory mediators such as cyclooxygenase-2 and inducible nitric oxide synthase and proinflammatory cytokines were also reduced. Further, the results were supported by a remarkable reduction of Iba-1 and GFAP hyperactivity clearly suggests attenuation of microglial and astrocytic activation. Results of our study suggest that FA has promising neuroprotective effect against degenerative changes in PD, and the protective effects are mediated through its antioxidant and anti-inflammatory properties. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/26504373/Neuroprotective_potential_of_ferulic_acid_in_the_rotenone_model_of_Parkinson's_disease_ L2 - https://dx.doi.org/10.2147/DDDT.S90616 DB - PRIME DP - Unbound Medicine ER -