Exploration of Antidepressant Mechanism of Chaihu and Longgu Mulitang Based on cAMP/PKA/CREB/BDNF Signaling Pathway
10.13422/j.cnki.syfjx.20221709
- VernacularTitle:基于cAMP/PKA/CREB/BDNF信号通路探讨柴胡加龙骨牡蛎汤抗抑郁的作用机制
- Author:
Dike ZHAO
1
;
Jun NIU
1
;
Zhixin DU
1
;
Chunyu ZHOU
1
;
Shenao DING
1
;
Xiaodan DU
1
;
Liping YANG
1
;
Mengdi MAO
2
Author Information
1. Henan University of Chinese Medicine，Zhengzhou 450046，China
2. Zhengzhou Erqi District Center for Disease Control and Prevention，Zhengzhou 450052，China
- Publication Type:Journal Article
- Keywords:
Chaihu and Longgu Mulitang;
depression;
cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP-response element-binding protein （CREB）/brain-derived neurotrophic factor （BDNF） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(3):17-25
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the intervention effect of Chaihu and Longgu Mulitang （CLMT） on rat depression model prepared by chronic unpredictable mild stress （CUMS） based on cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP-response element-binding protein （CREB）-brain-derived neurotrophic factor （BDNF） signaling pathway. MethodSixty SD rats were divided into normal group， model group， and CLMT low-， medium- and high-dose groups and fluoxetine group （positive control） according to random number table. They， except the normal group， were treated with CUMS for 49 days to prepare the rat depression model. The CLMT low-， medium- and high-dose groups were given 2.89， 5.78 11.56 g·kg-1 of CHMD granules， respectively， and the fluoxetine group was given 2.06 mg·kg-1 of fluoxetine hydrochloride on the 29th day. The normal group and the model group received equal volume of normal saline for 21 days. The behavioral performance of rats were observed by open field test and forced swim test. The levels of 5-hydroxytryptamine （5-HT）， norepinephrine （NE） and cAMP in rat hippocampus were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of PKA， CREB， and BDNF in rat hippocampus were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of PKA and BDNF were detected by Western blot. Immunohistochemistry was used to determine the expression of CREB， and hematoxylin and eosin （HE） staining and Nissl staining were used to observe the morphological changes of hippocampus. ResultCompared with the conditions in the normal group， the immobility time of the model group in the forced swim test was increased （P<0.01） and the total movement distance， residence time in central area， number of entries in central area and movement distance in central area were decreased （P<0.01）. Additionally， the contents of 5-HT， NE and cAMP in hippocampus of the model group as well as the protein expressions of PKA， BDNF and CRE，the mRNA expressions of BDNF and CREB were lower than those in the normal group （P<0.01）. Compared with the model group， the CLMT groups had reduced immobility time （P<0.01）， elevated total movement distance， residence time in central area， number of entries in central area and movement distance in central area （P<0.05， P<0.01）， up-regulated contents of 5-HT， NE and cAMP in hippocampus （P<0.05， P<0.01）， and up-regulated protein expressions of PKA， BDNF and CREB and mRNA expressions of BDNF and CREB （P<0.01）. HE staining and Nissl staining showed that CLMT significantly improved the neuronal structure in rat hippocampus. ConclusionCLMT alleviates the anxiety and depression of rats. These effects may be mediated by regulating monoamine neurotransmitters 5-HT and NE in hippocampus of depressed rats， activating cAMP/PKA/CREB/BDNF signaling pathway， up-regulating the expression of BDNF and protecting hippocampal structure and function .
