20(S)-Protopanaxadiol Exerts Antidepressive Effects in Chronic Corticosterone-Induced Rodent Animal Models as an Activator of Brain-Type Creatine Kinase

• DOI: 10.1021/acs.jafc.4c00415
• Publication Date: 2024-04-25T11:08:53Z
• Authors: Zhu Zhu; Yao Cheng; Xu Han; Tiantian Wang; Hantao Zhang; Qi Yao; Feiyan Chen; Ling Gu; Dongqing Yang; Lin Chen; Yunan Zhao
• Keywords: Corticosterone; Creatine kinase

20(S)-Protopanaxadiol (PPD) is one of the bioactive ingredients in ginseng and possesses neuroprotective properties. Brain-type creatine kinase (CK-BB) an enzyme involved brain energy homeostasis via phosphocreatine–creatine system. We previously identified PPD as directly bound to CK-BB activated its activity vitro. In this study, we explored antidepressive effects that target CK-BB. First, conducted time course studies on CK-BB, behaviors, hippocampal structural plasticity responses corticosterone (CORT) administration. Five weeks CORT injection reduced protein levels induced depression-like behaviors impairment. Next, a CK inhibitor adeno-associated virus-targeting CKB were used diminish or expression brain. The loss led depressive morphological damage spines hippocampus. Then, polyclonal antibody against was determine distribution tissues. detected hippocampus cortex observed astrocytes, neurons, vascular endotheliocytes. Finally, different doses chronic CORT-induced depression model. Treatment with high dose significantly increased after long-term injection. addition, alleviated depressive-like by repeated Overall, our study revealed critical role mediating therapeutic for PPD, allowing us treat stress-related mood disorders.