Effect and mechanism of triptolide in alleviating depression induced by corticosterone in mice via CREB/BDNF/TrkB signaling pathway
- VernacularTitle:基于CREB/BDNF/TrkB信号通路探究雷公藤甲素改善皮质酮诱发小鼠抑郁的作用及机制
- Author:
Ya-ru ZHANG
1
;
Yao ZHUANG
;
Zhu TAO
;
Xue LI
;
Shu-min DING
;
Jin-peng LYU
;
Li LIU
Author Information
- Publication Type:Journal Article
- Keywords: triptolide; corticosterone; C57BL/6J mice; depression; apoptosis; autophagy; CREB/BD-NF/TrkB signaling pathway
- From: Chinese Pharmacological Bulletin 2025;41(4):677-685
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of triptolide(TP)on corticosterone(CORT)-induced depression-like behaviors in mice and explore the antidepressant mechanism of TP based on the CREB/BDNF/TrkB sig-naling pathway.Methods Sixty 8-week-old male C57BL/6J mice were randomly divided into five groups:control group,CORT group,TP groups of low and high doses(10,30 μg·kg-1),and fluoxetine(FLU)group(10 mg·kg-1).Except for the control group,the other groups received subcutaneous injec-tions of CORT for three consecutive weeks to establish the model of depression.During the last two weeks of modeling,normal saline,TP and FLU were adminis-tered via intraperitoneal injection respectively.After the administration,depression-like behaviors in mice were assessed using forced swimming test,tail suspen-sion test,and sucrose preference test.Biochemical methods were used to measure the levels of SOD and MDA in the hippocampus and prefrontal cortex(PFC).Cell apoptosis was detected by TUNEL meth-od.Immunohistochemistry,immunofluorescence,and Western blotting were employed to detect the expres-sion of apoptosis/autophagy-related proteins,synaptic structure markers,and proteins related to the CREB/BDNF/TrkB signaling pathway.Results TP signifi-cantly ameliorated CORT-induced depression-like be-haviors in mice,mainly manifested by reduced immo-bility time in the tail suspension test and forced swim-ming test,and increased sucrose preference rate.TP alleviated CORT-induced oxidative stress by increasing SOD levels and reducing MDA production in brain tis-sue.Additionally,TP also inhibited apoptosis and ex-cessive autophagy of neurons in the hippocampus and prefrontal cortex,maintained synaptic plasticity,and significantly upregulated the expression of p-CREB,BDNF,and TrkB.Conclusions TP exhibits potential antidepressant effect in mice by upregulating the CREB/BDNF/TrkB signaling pathway,reducing oxida-tive stress,inhibiting excessive neuronal apoptosis and autophagy,and improving synaptic plasticity.
