The neuroprotective effect of elderberry diet on the tramadol-induced toxicity in the hippocampus of adult male rats

Pain relievers such as tramadol are among the most commonly prescribed around the world. However, Long-term tramadol use has been shown to cause neurotoxicity, neuroinflammation, and cognitive impairment, which has limited its clinical use. Elderberry (EB), a plant extract widely recognized for its medicinal properties, is used in this study to investigate the effects of a plant-based diet on tramadol's adverse effects in the hippocampus region. The effects of EB oral diet on the devastating effects of tramadol on the hippocampus structure and function of 36 male albino rats were evaluated using behavioral, electrophysiological, and histological setups. Three groups (Control, Tramadol, and Tramadol+EB) were examined using behavioral, electrophysiological, and histological setups. The behavioral findings showed that the EB diet could improve most of the memory-related indices in Tramadol+EB compared to the Tramadol group. Regarding the fEPSP slope and population spike amplitude, these electrophysiological parameters returned to control levels in the Tramadol+EB group. Additionally, a decrease in caspase-3 expression was observed in hippocampal cells. While there was a reduction in astrogliosis in the Tramadol+EB group compared to the Tramadol group, no significant differences were noted in the morphological variations of astrocytes between the groups. In conclusion, although further studies are necessary to elucidate other aspects of EB's effects on the brain, it may be considered a potential neuroprotective agent in