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The effect of geniposide on chronic unpredictable mild stress‐induced depressive mice through BTK / TLR4 / NF‐κB and BDNF / TrkB signaling pathways
Author(s) -
Chen Tong,
Liu Shengnan,
Zheng Menglin,
Li Yixuan,
He Ling
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6846
Subject(s) - tlr4 , downregulation and upregulation , tropomyosin receptor kinase b , pharmacology , in vivo , corticosterone , signal transduction , nf κb , chemistry , bruton's tyrosine kinase , tumor necrosis factor alpha , endocrinology , medicine , neurotrophic factors , biology , receptor , biochemistry , tyrosine kinase , microbiology and biotechnology , hormone , gene
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.