Ellagic acid prevents 3-nitropropionic acid induced symptoms of Huntington’s disease

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2021-09, Vol.394 (9), p.1917-1928
• Main Authors: Sharma, Priya, Kumar, Manish, Bansal, Nitin
• Format: Article
• Language: English
• Subjects: 3-Nitropropionic acid; Acids; Animals; Antioxidants; Biomedical and Life Sciences; Biomedicine; Catalase; Catalase - metabolism; Cognition Disorders - prevention & control; Cognitive ability; Dehydrogenases; Disease Models, Animal; Dose-Response Relationship, Drug; Ellagic acid; Ellagic Acid - administration & dosage; Ellagic Acid - pharmacology; Functional foods & nutraceuticals; Glutathione; Glutathione - metabolism; Huntington Disease - prevention & control; Huntington's disease; Huntingtons disease; Male; Maze Learning - drug effects; Mitochondria; Mitochondria - drug effects; Neuroprotection; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Neurosciences; Nitro Compounds; Original Article; Oxidative stress; Pattern recognition; Pharmacology/Toxicology; Propionates; Rats; Rats, Wistar; Succinate dehydrogenase; Thiobarbituric acid
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-021-02106-1

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.