Abstract
Background: Chaihu-Shugan-San is a classical prescription to treat depression. According to the traditional Chinese medicine (TCM) principle, the 2 decomposed recipes in Chaihu-Shugan-San exert synergistic effects, including Shu Gan (stagnated Gan-Qi dispersion) and Rou Gan (Gan nourishment to alleviate pain). However, the specific mechanism of Chaihu-Shugan-San on depression and its compatibility rule remain to be explored. Objective: We aimed to explore the anti-depression mechanisms and analyze the advantage of TCM compatibility of Chaihu-Shugan-San. Methods: The chronic unpredictable mild stress (CUMS) rat model was established. Antidepressant effects were evaluated by sucrose preference test (SPT), and forced swimming test (FST). Tandem Mass Tag (TMT)-based quantitative proteomics of the hippocampus was used to obtain differentially expressed proteins (DEPs). Bioinformatics analysis including Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) networks was utilized to study the DEPs connections. At last, the achieved key targets were verified by western blotting. Results: Chaihu-Shugan-San increased weight gain and food intake, as well as exhibited better therapeutic effects including enhanced sucrose preference and extended immobility time when compared with its decomposed recipes. Proteomics showed Chaihu-Shugan-San, Shu Gan, and Rou Gan regulated 110, 12, and 407 DEPs, respectively. Compared with Shu Gan or Rou Gan alone, the expression of 22 proteins was additionally changed by Chaihu-Shugan-San treatment, whereas the expression of 323 proteins whose expression was changed by Shu Gan or Rou Gan alone were not changed by Chaihu-Shugan-San treatment. Bioinformatics analysis demonstrated that Chaihu-Shugan-San affected neurotransmitter’s release and transmission cycle (e.g., γ-aminobutyric acid (GABA), glutamate, serotonin, norepinephrine, dopamine, and acetylcholine). GABA release pathway is also targeted by the 22 DEPs. Unexpectedly, only 2 pathways were enriched by the 323 DEPs: Metabolism and Cellular responses to external stimuli. Lastly, the expression of Gad2, Vamp2, and Pde2a was verified by western blotting. Conclusions: Chaihu-Shugan-San treats depression via multiple targets and pathways, which may include regulations of 110 DEPs and some neurotransmitter’s transmission cycle. Compared with Shu Gan and Rou Gan, the 22 Chaihu-Shugan-San advanced proteins and the affected GABA pathway may be the advantages of Chaihu-Shugan-San compatibility. This research offers data and theory support for the clinical application of Chaihu-Shugan-San.
Highlights
Depression is one of the most pervasive, disabling, and expensive of all neuropsychiatric disorders (Porcu et al, 2020)
The weight gain (F5,42 31.792, p < 0.01) and food intake (F5,42 5.033, p < 0.01) of the ChaihuShugan-San group, the fluoxetine group, and the Shu Gan group was significantly higher in comparison with the model group (p < 0.05) (Figures 3A,B)
Compared with Shu Gan or Rou Gan alone, the expression of 22 advanced proteins was changed by Chaihu-Shugan-San treatment, whereas the expression of 323 proteins whose expression was changed by Shu Gan or Rou Gan alone were not changed by Chaihu-Shugan-San treatment
Summary
Depression is one of the most pervasive, disabling, and expensive of all neuropsychiatric disorders (Porcu et al, 2020). Chaihu-Shugan-San, a classic TCM prescription was written in Jing Yue Quan Shu, has been extensively utilized in Chinese clinical applications for the treatment of depression (Liu et al, 2020). Other researches support that Chaihu-Shugan-San exerts antidepressant effect by increasing monoamine neurotransmitters, regulating brainderived neurotrophic factor (BDNF), and affecting the BDNFTrkB-ERK/Akt signalling pathway (Li et al, 2009; Qiu et al, 2014b; Liu Q. et al, 2018; Chen et al, 2018) Despite these researches, the mechanisms of the multi-component ChaihuShugan-San are far from being fully understood, which limits its application. The specific mechanism of Chaihu-Shugan-San on depression and its compatibility rule remain to be explored
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.