Abstract
Mitochondrial abnormalities and redox imbalance are major pathogenic factors in progression of Huntington’s disease (HD), manifested clinically by affective, motor, cognitive, and psychiatric incompetence. Antioxidants behold much promise in mitigation of several pathological facets in HD. Ellagic acid (EA) is a naturally derived polyphenol acknowledged for potent neuroprotective abilities that enabled its significance amongst popular brain tonics. The present study is aimed to examine the outcome of EA pre-treatment in 3-nitropropionic acid (3-NP) rat prototype of HD. Separate rat groups were pre-treated with EA (25, 50, and 100 mg/kg, p.o.) for 21 days and 3-NP (10 mg/kg, i.p.) was given for 14 days alongside to induce symptoms of HD. The physical/motor functions (narrow beam paradigm, footprint study, hanging-wire assessment) and cognitive abilities using elevated plus maze and novel object recognition task were evaluated. Entire brain was isolated and succinate dehydrogenase activity and parameters of oxido-nitrosative stress were assessed in mitochondrial fraction. 3-NP accrued oxido-nitrosative stress and significant decrease in succinate dehydrogenase activity caused motor and cognitive deficits in rats. EA pre-treatment resurrected succinate dehydrogenase activity in 3-NP treated rats that indicated preservation of mitochondrial function. A significant decrease in thiobarbituric acid reactive substances and nitrite levels and increase in glutathione and catalase activity by EA in 3-NP treated rats was noted. EA protected the rats against 3-NP triggered cognitive insufficiency and motor disturbances. It can be inferred that ellagic acid protects against 3-NP induced mitochondrial dysfunction and oxido-nitrosative stress in the brain. EA supplements or nutraceuticals might possess protective potential against symptoms of HD.
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The authors are thankful to the management of A.S.B.A.S.J.S.M. College of Pharmacy, Bela (Ropar) for providing the necessary research facilities.
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NB conceived and designed this research. PS and MK conducted experiments. MK drafted the original and revised manuscript. All authors read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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This study was approved by the “Institutional Animal Ethics Committee (IAEC)” of the A.S.B.A.S.J.S.M. College of Pharmacy, Bela (Ropar) vide protocol no. ASCB/IAEC/09/16/113 (dated: 24–09-2016). The guidelines of “The Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA),” Ministry of Forests & Environment, and Government of India (New Delhi) were followed for all animal experiments and care of animals.
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Sharma, P., Kumar, M. & Bansal, N. Ellagic acid prevents 3-nitropropionic acid induced symptoms of Huntington’s disease. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1917–1928 (2021). https://doi.org/10.1007/s00210-021-02106-1
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DOI: https://doi.org/10.1007/s00210-021-02106-1