Department of Pharmacology, China Pharmaceutical University, Nanjing, China.
Phytother Res. 2021 Feb;35(2):932-945. doi: 10.1002/ptr.6846. Epub 2020 Nov 8.
The purpose of this study was to estimate the pharmacological effect of geniposide (GEN) on depression, caused by chronic unpredictable mild stress (CUMS), and explore its potential mechanism. During the 6 week CUMS procedure, the mice were treated with GEN (10, 40 mg/kg) by gavage once daily for 3 weeks. As a result, the GEN treatment remarkably improved the behavioral manifestations and suppressed the generations of inflammatory cytokines both in vivo and in vitro. The MDA level was significantly increased, while the activities of SOD, GSH-PX were decreased in CUMS-challenged mice and corticosterone-stimulated PC12 cells. GEN administration significantly inhibited those changes. Moreover, GEN treatment could downregulate the expressions of p-BTK, TLR4, MyD88, p-NF-κB proteins, and upregulate BDNF, p-TrkB generations in CUMS-induced mice. Moreover, GEN administration inhibited the protein levels of p-BTK, TLR4, MyD88, p-NF-κB in corticosterone-induced PC12 cell. In summary, the results suggested that GEN exerted a therapeutic effect on CUMS-induced depressive mice possibly through the regulation of BTK/TLR4/NF-κB and BDNF/TrkB signaling pathways.
本研究旨在评估栀子苷（GEN）对慢性不可预测轻度应激（CUMS）引起的抑郁的药理作用，并探讨其潜在机制。在 6 周 CUMS 处理过程中，通过灌胃每天给予 GEN（10、40mg/kg）一次，连续 3 周。结果表明，GEN 治疗显著改善了体内和体外的行为表现，并抑制了炎症细胞因子的产生。CUMS 应激小鼠和皮质酮刺激的 PC12 细胞中 MDA 水平显著升高，而 SOD、GSH-PX 活性降低。GEN 给药显著抑制了这些变化。此外，GEN 治疗可下调 CUMS 诱导小鼠中 p-BTK、TLR4、MyD88、p-NF-κB 蛋白的表达，并上调 BDNF、p-TrkB 的产生。此外，GEN 给药抑制了皮质酮诱导的 PC12 细胞中 p-BTK、TLR4、MyD88、p-NF-κB 的蛋白水平。综上所述，这些结果表明，GEN 通过调节 BTK/TLR4/NF-κB 和 BDNF/TrkB 信号通路对 CUMS 诱导的抑郁小鼠发挥治疗作用。
