%0 Journal Article
%T Shuganheweitang Ameliorates Chronic Unpredictable Mild Stress-Induced Depression-Like Behaviors in Rats through the PI3K/AKT/mTOR Pathway: Involvement of Amino Acids, Glycerophospholipids, and Energy Metabolism
%A Qi Li
%A Junjie Hu
%A Zhenpeng Qiu
%A Juan Li
%A Misi Zhou
%A Xiao Huang
%A Di He
%A Chuanyu Yuan
%A Kang Yin
%A Yanwen Liu
%A Songlin Liu
%A Xin Chen
%J Chinese Medicine
%P 13-55
%@ 2151-1926
%D 2023
%I Scientific Research Publishing
%R 10.4236/cm.2023.141002
%X <b><span style=\"font-family:;\" \"=\"\">Background:</span></b><span style=\"font-family:;\" \"=\"\"> Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT)
is a clinical formula that effectively treats depression. However, the
potential mechanism used by SGHWT to ameliorate depression-like behaviors is
still unclear. This study investigated the effects of SGHWT on metabolic change
in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced
depression in rats to explore the mechanism of the anti-depressive effect. </span><b><span style=\"font-family:;\" \"=\"\">Methods:</span></b><span style=\"font-family:;\" \"=\"\"> A total of 52 rats were u<span>sed to
create a model of depression by CUMS combined with solitary rearing for 6
weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test
(FST), and body weight (BW) were performed to analyze the pharmacodynamic
effects of SGHWT. H&amp;E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate th</span>e
mechanism of action. Untargeted metabolomics techniques by ultra-performance
liquid chromatography-quantitative time-of-flight tandem mass spectrometry
(UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the
liver and hypothalamus. </span><b><span style=\"font-family:;\" \"=\"\">Results:</span></b><span style=\"font-family:;\" \"=\"\"> SGHWT improved CUMS-induced depression-like behaviors <i>in vivo</i>. SGHWT reduced hepatic c-Fos
protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and
p-mTOR protein expressions were significantly downregulated in the liver
and hypothalamus of CUMS rats. Notably, these alterations were reversed by the
SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5
key differential SPT-associated metabolites in the liver and hypothalamus,
respectively. </span><b><span style=\"font-family:;\" \"=\"\">Conclusion: </span></b><span style=\"font-family:;\" \"=\"\">This study suggests that SGHWT ameliorates chronic unpredictable mild
stress-induced depression-like behaviors, by the involvement of amino acids,
glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. <b>Highlights:</b> 1) Shuganheweitang was derived from the TCM
herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors
in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and
hypothalamus metabolomics. 4) SGHWT regulates amino
%K Shuganheweitang
%K Chronic Unpredictable Mild Stress
%K Depression
%K Metabolomics
%K PI3K/AKT/mTOR
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=123948