PMID- 36353500
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221111
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Chaigui granule exerts anti-depressant effects by regulating the synthesis of 
      Estradiol and the downstream of CYP19A1-E2-ERKs signaling pathway in CUMS-induced 
      depressed rats.
PG  - 1005438
LID - 10.3389/fphar.2022.1005438 [doi]
LID - 1005438
AB  - Background: There is a significant gender difference in the prevalence of 
      depression. Recent studies have shown that estrogen plays a crucial role in 
      depression. Therefore, studying the specific mechanism of estrogen's role in 
      depression can provide new ideas to address the treatment of depression. Chaigui 
      granule has been shown to have exact antidepressant efficacy, and the contents of 
      saikosaponin (a, b(1), b(2), d) and paeoniflorin in Chaigui granule are about 
      0.737% and 0.641%, respectively. Some studies have found that they can improve 
      depression-induced decrease in testosterone (T) levels ( approximately 36.99% decrease compared 
      to control). However, whether Chaigui granule can exert antidepressant efficacy 
      by regulating estrogen is still unclear. This study aimed to elucidate the 
      regulation of estrogen levels by Chaigui granule and the underlying mechanism of 
      its anti-depressant effect. Methods: Eighty-four male Sprague-Dawley (SD) rats 
      were modeled using a chronic unpredictable mild stress (CUMS) procedure. The 
      administration method was traditional oral gavage administration, and behavioral 
      indicators were used to evaluate the anti-depressant effect of Chaigui granule. 
      Enzyme-linked immunosorbent assay (ELISA) was adopted to assess the modulating 
      impact of Chaigui granule on sex hormones. Then, reverse 
      transcription-quantitative PCR (RT-qPCR), and Western blot (WB) techniques were 
      employed to detect extracellular regulated protein kinases (ERK) 
      signaling-related molecules downstream of estradiol in the hippocampus tissue. 
      Results: The administration of Chaigui granule significantly alleviated the 
      desperate behavior of CUMS-induced depressed rats. According to the results, we 
      found that Chaigui granule could upregulate the level of estradiol (E2) in the 
      serum ( approximately 46.56% increase compared to model) and hippocampus ( approximately 26.03% increase 
      compared to model) of CUMS rats and increase the levels of CYP19A1 gene and 
      protein, which was the key enzyme regulating the synthesis of T into E2 in the 
      hippocampus. Chaigui granule was also found to have a significant back-regulatory 
      effect on the gene and protein levels of ERbeta, ERK1, and ERK2. Conclusion: Chaigui 
      granule can increase the synthesis of E2 in the hippocampus of CUMS-induced 
      depressed rats and further exert antidepressant effects by activating the 
      CYP19A1-E2-ERKs signaling pathway.
CI  - Copyright (c) 2022 Tian, Qin, Xu, Gao, Zhou, Gao, Qin and Ren.
FAU - Tian, Jun-Sheng
AU  - Tian JS
AD  - Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi 
      Medical University, Taiyuan, China.
FAU - Qin, Peng-Fei
AU  - Qin PF
AD  - Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi 
      Medical University, Taiyuan, China.
FAU - Xu, Teng
AU  - Xu T
AD  - Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi 
      Medical University, Taiyuan, China.
FAU - Gao, Yao
AU  - Gao Y
AD  - Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi 
      Medical University, Taiyuan, China.
FAU - Zhou, Yu-Zhi
AU  - Zhou YZ
AD  - Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi 
      Medical University, Taiyuan, China.
FAU - Gao, Xiao-Xia
AU  - Gao XX
AD  - Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi 
      Medical University, Taiyuan, China.
FAU - Qin, Xue-Mei
AU  - Qin XM
AD  - Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi 
      Medical University, Taiyuan, China.
FAU - Ren, Yan
AU  - Ren Y
AD  - Department of Psychiatry, Shanxi Bethune Hospital, Shanxi Academy of Medical 
      Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, 
      Taiyuan, China.
AD  - Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
DEP - 20221024
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9637986
OTO - NOTNLM
OT  - CYP19A1-E2-ERKs signaling pathway
OT  - chaigui granule
OT  - chronic unpredictable mild stress
OT  - depression
OT  - xiaoyao san
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/11 06:00
MHDA- 2022/11/11 06:01
PMCR- 2022/10/24
CRDT- 2022/11/10 02:19
PHST- 2022/07/28 00:00 [received]
PHST- 2022/10/10 00:00 [accepted]
PHST- 2022/11/10 02:19 [entrez]
PHST- 2022/11/11 06:00 [pubmed]
PHST- 2022/11/11 06:01 [medline]
PHST- 2022/10/24 00:00 [pmc-release]
AID - 1005438 [pii]
AID - 10.3389/fphar.2022.1005438 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Oct 24;13:1005438. doi: 10.3389/fphar.2022.1005438. 
      eCollection 2022.