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Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation of β-Arrestin 2-Mediated Pathways in Hippocampus.

Zhu X, Xia O, Han W, Shao M, Jing L, Fan Q, Liu Y, Diao J, Lv Z, Sun X - Evid Based Complement Alternat Med (2014)

Bottom Line: XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT.XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2.In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou 510515, China ; The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.

ABSTRACT
Xiao Yao San (XYS) is a classical Chinese medicine formula that has been widely used to treat mood disorders for hundreds of years. To confirm the effect of XYS and better understand its underlying mechanism, high-performance liquid chromatography-mass spectrometry analysis-based quality control of XYS extracts and proteomics-based identification of differential proteins in the hippocampus were adopted in social isolation and chronic unpredictable mild stress- (CUMS-) treated rats. The depressive-like behavior of rats induced by CUMS resembled the manifestation of human depression. The upregulated corticosterone (CORT) and urocortin 2 (UCN2) levels demonstrated the existence of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT. XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2. The expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and mammalian target of rapamycin (mTOR) were also elevated by XYS. In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2. The upregulation of BDNF/TrkB and the phosphorylation of mTOR require β-arrestin 2 as a scaffold to regulate stress signaling.

No MeSH data available.


Related in: MedlinePlus

2D gel images of protein expression and MALDI-TOF MS identification of samples from the hippocampus. 2D gel image of protein expression (a). Mascot search results of spot 7 (b). MALDI-TOF MS was obtained from spot 7 after trypsin digestion (c). 2DE, 2D electrophoresis, MALDI-TOF MS, and matrix-assisted laser desorption/ionization time of flight mass spectrometry.
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fig5: 2D gel images of protein expression and MALDI-TOF MS identification of samples from the hippocampus. 2D gel image of protein expression (a). Mascot search results of spot 7 (b). MALDI-TOF MS was obtained from spot 7 after trypsin digestion (c). 2DE, 2D electrophoresis, MALDI-TOF MS, and matrix-assisted laser desorption/ionization time of flight mass spectrometry.

Mentions: Based on the reproducible 2D gel electrophoresis, two downregulated and eight upregulated spots were observed in the model group unlike the control group (Figure 5(a)). The two upregulated spots by XYS were identified as prohibitin and proteasome subunit beta type-6. Among the eight spots downregulated by XYS, five spots were identified as tubulin alpha-1A chain, DCN1-like protein 3, serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform (PP2Ab), tubulin beta-2C chain, sodium channel, and clathrin linker 1 (Table 1). Figure 5(b) illustrates the peptide mass fingerprint obtained from the seven spots. Figure 5(c) shows the mascot research results.


Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation of β-Arrestin 2-Mediated Pathways in Hippocampus.

Zhu X, Xia O, Han W, Shao M, Jing L, Fan Q, Liu Y, Diao J, Lv Z, Sun X - Evid Based Complement Alternat Med (2014)

2D gel images of protein expression and MALDI-TOF MS identification of samples from the hippocampus. 2D gel image of protein expression (a). Mascot search results of spot 7 (b). MALDI-TOF MS was obtained from spot 7 after trypsin digestion (c). 2DE, 2D electrophoresis, MALDI-TOF MS, and matrix-assisted laser desorption/ionization time of flight mass spectrometry.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4109698&req=5

fig5: 2D gel images of protein expression and MALDI-TOF MS identification of samples from the hippocampus. 2D gel image of protein expression (a). Mascot search results of spot 7 (b). MALDI-TOF MS was obtained from spot 7 after trypsin digestion (c). 2DE, 2D electrophoresis, MALDI-TOF MS, and matrix-assisted laser desorption/ionization time of flight mass spectrometry.
Mentions: Based on the reproducible 2D gel electrophoresis, two downregulated and eight upregulated spots were observed in the model group unlike the control group (Figure 5(a)). The two upregulated spots by XYS were identified as prohibitin and proteasome subunit beta type-6. Among the eight spots downregulated by XYS, five spots were identified as tubulin alpha-1A chain, DCN1-like protein 3, serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform (PP2Ab), tubulin beta-2C chain, sodium channel, and clathrin linker 1 (Table 1). Figure 5(b) illustrates the peptide mass fingerprint obtained from the seven spots. Figure 5(c) shows the mascot research results.

Bottom Line: XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT.XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2.In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2.

View Article: PubMed Central - PubMed

Affiliation: Department of Traditional Chinese Medicine, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou 510515, China ; The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.

ABSTRACT
Xiao Yao San (XYS) is a classical Chinese medicine formula that has been widely used to treat mood disorders for hundreds of years. To confirm the effect of XYS and better understand its underlying mechanism, high-performance liquid chromatography-mass spectrometry analysis-based quality control of XYS extracts and proteomics-based identification of differential proteins in the hippocampus were adopted in social isolation and chronic unpredictable mild stress- (CUMS-) treated rats. The depressive-like behavior of rats induced by CUMS resembled the manifestation of human depression. The upregulated corticosterone (CORT) and urocortin 2 (UCN2) levels demonstrated the existence of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT. XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression of β-arrestin 2. The expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and mammalian target of rapamycin (mTOR) were also elevated by XYS. In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2. The upregulation of BDNF/TrkB and the phosphorylation of mTOR require β-arrestin 2 as a scaffold to regulate stress signaling.

No MeSH data available.


Related in: MedlinePlus