Neuroprotective effects of Caffeic acid phenethyl ester administered with levodopa and benserazide in a rat model of Parkinson’s disease

Introduction: Parkinson's disease (PD) is a neurological disorder caused by the pathological destruction of dopaminergic neurons.Although it is commonly associated with motor symptoms, most patients also experience a range of non-motor symptoms, including mental health issues such as anxiety, depression, and memory loss.In this study, we investigated the effect of caffeic acid phenethyl ester (CAPE) on improving PD and reducing the side effects of levodopa.Methods: Forty-nine male rats were randomly divided into seven groups.A PD model was induced by unilateral injection of 6-OHDA.A combination therapy involving three doses of CAPE (10, 20, and 40 mol/kg) was administered, along with levodopa and benserazide.The animals were assessed during the study using various behavioral tests, such as tail suspension swing, apomorphine-induced rotation, elevated plus-maze, and open field.Additionally, histological tests, including Nissl staining and tyrosine hydroxylase (TH) immunohistochemistry, were performed to evaluate the animals further.Results: Our research demonstrates that CAPE effectively reduces side effects associated with levodopa.Moreover, at higher doses, CAPE significantly improves non-motor symptoms, including anxiety and depression, in addition to enhancing motor function.Histological analysis also suggests a protective effect of CAPE on dopaminergic neurons in the substantia nigra. Conclusion:The findings of this study suggest that co-administration of CAPE can help prevent L-DOPA-induced anxiety-like behaviors through its neuroprotective properties.Therefore, CAPE may have the potential as an adjunct therapy for the management of PD.