Bavachin ameliorates neuroinflammation and depressive-like behaviors in streptozotocin-induced diabetic mice through the inhibition of PKCδ
Free radical biology & medicine(2024)
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 PKC delta and inhibited the activation of the NF-kappa B pathway in vivo and in vitro. Knockdown of PKC delta with siRNA-PKC delta partially reversed the inhibitory effect of bavachin on the NF-kappa B pathway and the level of pro-inflammatory factors. We further found that PKC delta 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 PKC delta to inhibit the NF-kappa B 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 PKC delta is a potential target for the treatment of diabetes-associated neuroinflammation, including depression.
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关键词
Depression,Diabetes,Bavachin,PKC delta,NF-kappa B
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