Affiliation:
1. Henan Key Laboratory of Neurorestoratology The First Affiliated Hospital of Xinxiang Medical University Xinxiang China
2. Department of Physiology and Pathophysiology, Sino‐UK Joint Laboratory of Brain Function and Injury of Henan Province, School of Basic Medical Sciences Xinxiang Medical University Xinxiang China
3. The Third Affiliated Hospital of Xinxiang Medical University Xinxiang China
4. Department of Blood Transfusion Xuchang Central Hospital Xuchang China
5. School of Biomedical Sciences University of Leeds Leeds UK
6. EA4245, Transplantation, Immunology and Inflammation, Faculty of Medicine University of Tours Tours France
7. Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Abstract
AbstractBackgroundOxidative stress is a well‐known pathological factor driving neuronal loss and age‐related neurodegenerative diseases. Melatonin, coenzyme Q10 and lecithin are three common nutrients with an antioxidative capacity. Here, we examined the effectiveness of them administrated individually and in combination in protecting against oxidative stress‐induced neuronal death in vitro, and neurodegenerative conditions such as Alzheimer's disease and associated deficits in vivo.MethodsMouse neuroblastoma Neuro‐2a (N2a) cells were exposed with H2O2 for 6 h, and subsequently treated with melatonin, coenzyme Q10, and lecithin alone or in combination for further 24 h. Cell viability was assessed using the CCK‐8 assay. Eight‐week‐old male mice were intraperitoneally injected with D‐(+)‐galactose for 10 weeks and administrated with melatonin, coenzyme Q10, lecithin, or in combination for 5 weeks starting from the sixth week, followed by behavioral tests to assess the effectiveness in mitigating neurological deficits, and biochemical assays to explore the underlying mechanisms.ResultsExposure to H2O2 significantly reduced the viability of N2a cells and increased oxidative stress and tau phosphorylation, all of which were alleviated by treatment with melatonin, coenzyme Q10, lecithin alone, and, most noticeably, by combined treatment. Administration of mice with D‐(+)‐galactose‐induced oxidative stress and tau phosphorylation, brain aging, impairments in learning and memory, anxiety‐ and depression‐like behaviors, and such detrimental effects were mitigated by melatonin, coenzyme Q10, lecithin alone, and, most consistently, by combined treatment.ConclusionsThese results suggest that targeting oxidative stress via supplementation of antioxidant nutrients, particularly in combination, is a better strategy to alleviate oxidative stress‐mediated neuronal loss and brain dysfunction due to age‐related neurodegenerative conditions.