FOLLOWUS
1.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing (102488), China
2.School of Basic Medicine Science, Beijing University of Chinese Medicine, Beijing (100102), China
3.Experiment Center, Encephalopathy Department, Affiliated Hospital of Shandong University of Chinese Medicine, Jinan (250014), China
Associate Prof. XU Xiang-qing, E-mail:happyxiangqing@163.com
纸质出版日期:2021-07-01,
网络出版日期:2019-11-29,
录用日期:2019-04-22
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Bo ZHANG, Hong-sheng CHANG, Kai-li HU, 等. Combination of Geniposide and Eleutheroside B Exerts Antidepressant-Like Effect on Lipopolysaccharide-Induced Depression Mice Model[J]. Chinese Journal of Integrative Medicine, 2021,27(7):534-541.
Bo ZHANG, Hong-sheng CHANG, Kai-li HU, et al. Combination of Geniposide and Eleutheroside B Exerts Antidepressant-Like Effect on Lipopolysaccharide-Induced Depression Mice Model[J]. Chinese Journal of Integrative Medicine, 2021,27(7):534-541.
Bo ZHANG, Hong-sheng CHANG, Kai-li HU, 等. Combination of Geniposide and Eleutheroside B Exerts Antidepressant-Like Effect on Lipopolysaccharide-Induced Depression Mice Model[J]. Chinese Journal of Integrative Medicine, 2021,27(7):534-541. DOI: 10.1007/s11655-019-3051-5.
Bo ZHANG, Hong-sheng CHANG, Kai-li HU, et al. Combination of Geniposide and Eleutheroside B Exerts Antidepressant-Like Effect on Lipopolysaccharide-Induced Depression Mice Model[J]. Chinese Journal of Integrative Medicine, 2021,27(7):534-541. DOI: 10.1007/s11655-019-3051-5.
Objective:
2
To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide (LPS)-induced depression mice model.
Methods:
2
Depression mice model was established by lipopolysaccharide (LPS) injection. Totally 48 mice were randomly divided into 6 groups (8 rats per group) according to a random number table
including normal
model
fluoxetine (20 mg/kg)
geniposide (100 mg/kg) + eleutheroside B (100 mg/kg)
geniposide + eleutheroside B + WAY 100635 (0.03 mg/kg)
geniposide + eleutheroside B+ N-methyl-D-aspartic acid receptor (NMDA
75 mg/kg) groups
respectively. After continuous administration for 10 days
autonomic activity tests after 30 min of administration were performed on the 10th day. On the 11th day
except for the normal group
the mice in the other groups were intraperitoneally injected with LPS (1 mg/kg)
and the behavioral tests were performed 4 h later. Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels in mice serum. The mRNA expression of indoleamine 2
3-dioxygenase (IDO) and nuclear transcription factor (NF-κB) were detected by real-time quantitative polymerase chain reaction. Western-blot analysis was used to detect IDO and NF-κB protein expressions in hippocampus tissue.
Results:
2
Compared with the normal group
a single administration of LPS increased the immobility time in the forced swimming test (FST) and tail suspension test (TST
P
<
0.01)
without affecting autonomous activity. Compared with the model group
fluoxetine and geniposide + eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST
decreased serum IL-1β content
inhibited the expression levels of NF-κB gene and protein in hippocampus tissues (
P
<
0.05 or
P
<
0.01). Compared with the model group
geniposide + eleutheroside B treatment significantly reduced serum TNF-α content and inhibited IDO mRNA and protein expressions in hippocampus (
P
<
0.05 or
P
<
0.01). In addition
NMDA partly prevented the inhibition of IDO mRNA expression by geniposide + eleutheroside B; NMDA and WAY-100635 also partly prevented the reduction of IL-1β content induced by geniposide + eleutheroside B treatment (
P
<
0.05 or
P
<
0.01).
Conclusions:
2
The combination of geniposide and eleutheroside B showed a certain antidepression-like effect. Its main mechanism of action may be contributed to inhibiting the activation of NF-κB
decreasing the proinflammatory cytokines such as TNF-α
IL-1β
and inhibiting in the neuroinflammatory reaction. Additionally
it also affects tryptophan metabolism
reduces the expression of a key enzyme of tryptophan metabolism
IDO. And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.
geniposideeleutheroside Bantidepressant effectmechanism5-hydroxytryptamineglutamate
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