Affiliation:
1. Jiangsu Provincial Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine
2. Jinling Institute of Technology
3. Jiangsu Province Hospital of Chinese Medicine,Affiliated Hospital of Nanjing University of Chinese Medicine
Abstract
Abstract
Background: High mobility group box1 (HMGB1)is a chromatin-binding protein that especially regulates inflammatory signaling cascades. Several reports have demonstrated the anti-inflammatory effect of hesperidin. Whether hesperidin attenuates radiation-induced brain injury via inhibiting HMGB1-mediated neuroinflammation remains unclear.
Methods: Morris water maze test and the step-down passive avoidance test were applied to evaluate whether hesperidin could relieve the irradiation-induced cognitive dysfunction. Nissl staining, western blotting and immunofluorescence were performed to uncover the mechanisms.
Results: In this study, we found that radiation reduced the neuronal number and increased the content of the proinflammatory cytokines in the hippocampus, and hesperidin significantly reversed these changes. More importantly, hesperidin significantly improved the learning and memory abilities of X-ray-stimulated mice. We also found that radiation markedly increased Iba-1 expression in the hippocampus and resulted in substantial translocation of HMGB1 from the nucleus to the cytoplasm in the hippocampus and BV-2 cell, and hesperidin reversed the radiation-induced upregulation of Iba-1 and the cytoplasmic translocation of HMGB1. Moreover, hesperidin rescued the radiation-induced the upregulations in the phosphorylation levels of ERK, p38 and p65 in the hippocampus.
Conclusions: This study demonstrated that hesperidin alleviated the radiation-induced cognitive dysfunction via inhibiting HMGB-mediated neuroinflammation, and indicated that hesperidin could be a promising candidate for treatment of radiation- induced brain injury.
Publisher
Research Square Platform LLC