Ganmai Dazao Tang Treats Breast Cancer-related Depression via MAPK/NF-κB Signling Pathway
10.13422/j.cnki.syfjx.20242122
- VernacularTitle:基于MAPK/NF-κB信号通路探讨甘麦大枣汤对乳腺癌相关抑郁症的治疗作用及机制
- Author:
Jieyuan LIU
1
;
Yanli WANG
1
;
Delian NIU
1
;
Mengting LI
1
;
Lijinchuan DONG
1
;
Xinmin LIU
2
;
Hongping HOU
1
;
Guangping ZHANG
1
;
Ying CHEN
1
;
Bo PENG
1
Author Information
1. Institute of Chinese Materia Medica， China Academy of Chinese Medical Sciences， Beijing 100700， China
2. Institute of Drug Discovery Technology， Ningbo University， Ningbo 315211， China
- Publication Type:Journal Article
- Keywords:
Ganmai Dazao Tang;
depression;
kynurenine/tryptophan （Kyn/Trp）;
neuroinflammation;
p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor-κB （NF-κB）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(23):170-178
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the therapeutic effect of Ganmai Dazao Tang on breast cancer-related depression and explore the mechanism of the decoction in regulating immune inflammation and neurotransmitters via the mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） pathway. MethodBALB/c mice were randomized into control， model， fluoxetine （5 mg·kg-1·d-1）， and low- and high-dose （crude drug 20 and 40 g·kg-1， respectively） Ganmai Dazao Tang groups （n=10）. The mouse model of 4T1 orthotopic transplantation-induced breast cancer-related depression-like behavior was established. The depression-like behavior of mice was assessed by the tail suspension test and the forced swimming test. RT-qPCR was employed to determine the mRNA levels of interleukin （IL）-17A， forkhead box P3 （FoxP3），IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in the cerebral cortex. Flow cytometry was employed to measure the proportions of immune cell subsets in the spleen and thymus. HPLC-MS/MS was employed to measure neurotransmitter levels in the cerebral cortex. Western blotting was employed to detect the activation of the MAPK/NF-κB pathway. ResultCompared with the model group， administration of Ganmai Dazao Tang at a dose of 40 g crude drug·kg-1 continuously for 4 weeks shortened the immobility time of modeled mice in the tail suspension and forced swimming tests （P<0.05）， down-regulated the mRNA levels of IL-1β， IL-17A， and TNF-α （P<0.05）， increased the proportions of T cells， CD4+ T cells， B cells， helper T 17 （Th17） cells， and regulatory T （Treg） cells， and reduced the proportion of CD8+ T cells （P<0.05）. Furthermore， it lowered the levels of 5-hydroxyindoleacetic acid （5-HIAA） and kynurenine （Kyn）， decreased the kynurenine/tryptophan （Kyn/Trp） ratio （P<0.05）， increased the content of 5-hydroxytryptamine （5-HT）， and down-regulated the protein levels of phosphorylated extracellular signal-regulated kinase （p-ERK）， phosphorylated p38 MAPK， and phosphorylated nuclear factor-κB p65 （P<0.05）. ConclusionGanmai Dazao Tang can down-regulate the expression of inflammatory cytokines such as IL-1β， IL-17A， and TNF-α， restore 5-HT metabolism and Kyn/Trp balance， increase the 5-HT content， and reduce the activation of p38 MAPK， ERK， and the MAPK-mediated NF-κB signaling pathway to reduce neuroinflammation in the treatment of cancer-related depression.
