Antioxidant activity of trimethoxy-substituted monocarbonyl analogues of curcumin in experimental Alzheimer’s disease in Wistar rats

Introduction. Alzheimer’s disease is a terminal form of dementia, the treatment of which is a significant medical problem, which requires the development of new drugs to correct this condition. Antioxidants may be one of such promising groups.

Aim: To assess the antioxidant properties of monocarbonyl analogues of curcumin in the conditions of experimental Alzheimer’s disease.

Material and Methods. Alzheimer’s disease was modeled in Wistar rats of both genders by injection A_ß1-42 aggregates into the CA1 part of the hippocampus of animals. The analyzed compounds are (1E, 4E)-1.5-bis (3,4,5-trimethoxyphenyl) penta1,4-diene-3-one and (1E, 4E)-1.5-bis (2,4,6-trimethoxyphenyl) penta-1,4-diene-3-one at a dose of 20 mg/kg orally and the reference donepezil at a dose of 50 mg / kg, orally was administered for 30 days from the moment of surgery. After this time, changes in the activity of endogenous antioxidant defense enzymes: superoxide dismutase, glutathione peroxidase and catalase were evaluated in rats in hippocampal tissue, and changes in the concentration of mitochondrial hydrogen peroxide and active products reacting with 2-thiobarbituric acid were also determined.

Results. During the study, it was shown that the use of the analyzed compounds and the reference contributed to an increase in the activity of antioxidant enzymes in hippocampal tissue in rats. At the same time, in animals (both sexes) treated by (1E, 4E)-1.5-bis (3,4,5-trimethoxyphenyl) penta-1,4-diene-3-one and (1E, 4E)-1.5-bis (2,4,6-trimethoxyphenyl) penta-1,4-diene-3-one, the activity of superoxide dismutase was higher (p < 0.05), than in animals treated by donepezil. Also, administration of the analyzed substances, a decrease in the concentration of mitochondrial hydrogen peroxide and active products reacting with 2-thiobarbituric acid was found, which was significantly (p < 0.05) lower when donepezil were administered.

Conclusion. The study showed that the monocarbonyl analogues of curcumin have an antioxidant effect in the conditions of experimental Alzheimer’s disease, while surpassing the reference donepezil. Based on the obtained data, it is reasonable to assume the relevance of further studies analyzing monocarbonyl curcuminoids as a remedies of pathogenetic therapy of Alzheimer’s disease.

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