Rinsenoside Rg1 and its involvement in Hippo–YAP signaling pathway alleviating symptoms of depressive-like behavior

作者：Linyin Gao, Jiarong Wang, Xiuchang Liu, Lei Wu, Ran Ding, Xuemei Han, X. F. Wang, Hao Ma, Jie Pan, Xiujun Zhang, Haitao Wang, Xueliang Shang · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-99587-4 · 被引用次数：5 · 研究领域：Hippo pathway signaling and YAP/TAZ、Wnt/β-catenin signaling in development and cancer、Hereditary Neurological Disorders

Ginsenoside Rg1 (G-Rg1) has potential antidepressant effects, but the underlying mechanism remains unclear. Presently, sixty 6-8 week-old male C57BL/6 mice were selected and randomly allocated to control, chronic restraint stress (CRS), CRS and low G-Rg1 administration (CRS + L-Rg1), CRS and high G-Rg1 administration (CRS + H-Rg1), and CRS and fluoxetine administration (CRS + FLX) groups. The component of anxiety in psychic processes and neuropathological changes occurring in dentate gyrus (DG) neurons were evaluated, where PC12 cells were assessed for the expression of G-Rg1. Both cell viability and apoptosis were analyzed. G-Rg1 (5 and 10 mg/kg/day) alleviated the behavioral manifestations of neuropathological processes revealed in DG neurons of CRS-induced mice. Western blotting analysis demonstrated the negative correlation of G-Rg1 level and that of Hipp-YAP signaling pathway components including p-YAP/YAP, p-MST1/MST1, and p-LATS1/LATS1, which were triggered by CRS. Combined therapy with G-Rg1 (10 mM) proved to have an inhibitory effect on PC12 cell viability and apoptosis compared to sole cort treatment. In addition, chronic G-Rg1 also reduced the protein expression levels of Hippo-YAP signaling pathway activated by corticosterone (Cort) including p-YAP/YAP, p-MST1/MST1, and p-LATS1/LATS1. The above mentioned improvements could be implemented due to XMU-MP-1 hampering the processes in Hippo-YAP signaling pathway. Importantly, the changes in synaptic plasticity and apop...