神经炎症
链脲佐菌素
糖尿病
药理学
抗抑郁药
氧化应激
蛋白激酶C
小胶质细胞
化学
医学
内分泌学
信号转导
内科学
炎症
海马体
生物化学
作者
Zhonghong Zhang,Lingyun Sun,Yiqun Guo,Jie Zhao,Jiaqi Li,Xiaohong Pan,Z. G. Li
标识
DOI:10.1016/j.freeradbiomed.2024.01.010
摘要
Depression and diabetes are closely linked; however, the pathogenesis of depression associated with diabetes is unclear, and there are no clinically effective antidepressant drugs for diabetic patients with depression. Bavachin is an important active ingredient in Fructus Psoraleae. In this study, we evaluated the anti-neuroinflammatory and antidepressant effects associated with diabetes and the molecular mechanisms of bavachin in a streptozotocin-induced diabetes mouse model. We found that bavachin clearly decreased streptozotocin (STZ)-induced depressive-like behaviors in mice. It was further found that bavachin significantly inhibited microglia activation and the phosphorylation level of PKCδ and inhibited the activation of the NF-κB pathway in vivo and in vitro. Knockdown of PKCδ with siRNA-PKCδ partially reversed the inhibitory effect of bavachin on the NF-κB pathway and the level of pro-inflammatory factors. We further found that PKCδ directly bound to bavachin based on molecular docking and pull-down assays. We also found that bavachin improved neuroinflammation-induced neuronal survival and functional impairment and that this effect may be related to activation of the ERK and Akt pathways mediated by the BDNF pathway. Taken together, these data suggested that bavachin, by targeting inhibition PKCδ to inhibit the NF-κB pathway, further reduced the inflammatory response and oxidative stress and subsequently improved diabetic neuronal survival and function and finally ameliorated diabetes-induced depressive-like behaviors in mice. For the first time, we found that bavachin is a potential agent for the treatment of diabetes-associated neuroinflammation and depression and that PKCδ is a potential target for the treatment of diabetes-associated neuroinflammation, including depression.
科研通智能强力驱动
Strongly Powered by AbleSci AI