Investigation of the effect of co-administration of caffeic acid and memantine on cell viability in oxidative stress induced by hydrogen peroxide in glioblastoma cells

Alzheimer's disease is a neurodegenerative condition affecting approximately 30 million people and is the most common among the elderly. Currently, there is no definitive cure for this disease, as the existing medications only slow down the neurodegenerative process in Alzheimer's. The molecular mechanisms underlying the pathogenesis of Alzheimer's disease have not been fully elucidated yet. Polyphenols are known to have various pharmaceutical properties, including being natural antioxidants in the human diet, neuroprotective, anti-inflammatory, anti-proliferative, and possessing free radical scavenging activities, as well as cardioprotective properties. These antioxidant compounds have the ability to eliminate free radicals produced within cells, which provides protective effects against neurodegenerative diseases. The widely used Alzheimer's treatment, memantine, has different pharmacological properties, including antioxidant features. When applied in conjunction with caffeic acid, it can contribute to improving overall daily functions and preventing disease progression. Recently, combination therapies involving NMDA receptor antagonists and neuroprotective agents have been shown to be an effective approach in preventing Alzheimer's disease. Therefore, in our study, we aimed to investigate the neuroprotective effects of a combination of the organic compound caffeic acid, a significant representative of hydroxycinnamic acids, and memantine, an NMDA receptor antagonist, against oxidative damage induced by H2O2 in glioblastoma U-118 MG cells. U-118 MG cells were exposed to oxidative stress by treating them with H2O2 after pretreatment with memantine and caffeic acid. Oxidative stress damage was induced by adding 200 µM H2O2 to the U-118 MG cell line, and the cells were incubated at 37°C for 24 hours. To investigate the protective effect of memantine and caffeic acid against oxidative stress induced by H2O2, four different study groups were established. Firstly, the effect of memantine and caffeic acid on cell viability was examined in the U-118 MG cell series. Then, the effective concentration of memantine and caffeic acid before and after application was determined in the formation of oxidative damage induced by H2O2 in the U-118 cell line. Finally, the effect of memantine and caffeic acid combination application on cell viability was investigated. The XTT method was applied to cell series for cell viability testing. As a result of our findings, it was observed that memantine does not have protective or therapeutic effects on cell damage induced by oxidative stress, while caffeic acid and combination applications showed protective or therapeutic effects at all doses in cell damage induced by oxidative stress. The neuroprotective and therapeutic effect of caffeic acid and combination applications may provide a new approach to drug development for the clinical treatment of neurodegenerative diseases.