The effect of geniposide on chronic unpredictable mild stress-induced depressive mice through BTK/TLR4/NF-κB and BDNF/TrkB signaling pathways
The effect of geniposide on chronic unpredictable mild stress-induced depressive mice through BTK/TLR4/NF-κB and BDNF/TrkB signaling pathways
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DOI：
10.1002/ptr.6846
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发表时间：
2020-11-08
影响因子：
7.2
通讯作者：
He, Ling
中科院分区：
文献类型：
--
作者：
Chen, Tong;Liu, Shengnan;He, Ling
本研究旨在评价京尼平苷（GEN）对慢性不可预见性轻度应激（CITS）所致抑郁症的药理作用，并探讨其可能的作用机制。在为期6周的CRTOS程序期间，通过管饲法每天一次用GEN（10、40 mg/kg）处理小鼠，持续3周。结果，GEN治疗显著改善了行为表现，并抑制了体内和体外炎性细胞因子的产生。皮质酮刺激的PC 12细胞和LPS刺激的小鼠MDA含量显著升高，SOD、GSH-PX活性显著降低。GEN给药显著抑制了这些变化。GEN能下调CNS诱导小鼠脑内p-BTK、TLR 4、MyD 88、p-NF-kappa B蛋白的表达，上调BDNF、p-Trk B代的表达。GEN还能抑制皮质酮诱导的PC 12细胞中p-BTK、TLR 4、MyD 88、p-NF-kappa B蛋白的表达。以上结果提示GEN可能通过调节BTK/TLR 4/NF-κ B和BDNF/Trk B信号通路发挥治疗作用。
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-kappa B 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-kappa B 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-kappa B and BDNF/TrkB signaling pathways.