Clavulanic Acid: A Novel Potential Agent in Prevention and Treatment of Scopolamine-Induced Alzheimer's Disease

Background and Aim: Alzheimer's disease (AD) is the most common form of dementia in the elderly. It is characterized as a multifaced disorder with a greater genetic contribution. The contribution of many genes such as BDNF, Sirtuin 6, and Seladin 1 has been reported in the pathogenesis of AD. Current therapies include acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, which are only temporarily beneficial. Therefore, it seems that more studies should be conducted to determine the exact mechanisms of drugs to deal with the diseases' multifactorial features that we face. Methods: In this study, 42 adult rats were randomly divided into 7 groups and received drugs intraperitoneally and orally according to the protocol as follows: scopolamine group, clavulanic acid group, memantine group, scopolamine + memantine group, clavulanic acid pre- and post-treatment, and normal saline group. The Morris water maze method was performed to evaluate the spatial memory of animals, and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay and real-time polymerase chain reaction were performed to study neuronal cell apoptosis and gene expression, respectively. Results: Significant differences were observed in the spatial memory of rats that received clavulanic acid prophylactically compared to the Alzheimer's model on the day of the test. Moreover, the results obtained during the training showed that both memantine and clavulanic acid improved spatial memory by increasing the time of rats present in the platform position and by reducing the swimming time in the scopolamine-induced Alzheimer's group. Besides, rats that received clavulanic acid and memantine had a greater percentage of healthy cells in comparison with the scopolamine-induced Alzheimer's group; however, the results were more significant for clavulanic acid. Furthermore, the expressions of BDNF, Seladin 1, and Sirtuin 6 as neuroprotective target genes were modified after clavulanic acid and memantine administrations; similarly, the results obtained from clavulanic acid were more significant. Conclusion: The results show that the administration of clavulanic acid before and after the use of scopolamine can reduce the percentage of apoptotic cells in the hippocampus and also improve the parameters related to learning and spatial memory; however, its effect in the prophylactic state was stronger. The results obtained from memantine revealed that it has neuroprotective potency against AD; however, clavulanic acid had a greater effect. Also, with increased expression of the neuroprotective genes, clavulanic acid could be considered as an option in the upcoming preclinical and clinical research about Alzheimer's disease.