title: Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation of β-Arrestin 2-Mediated Pathways in Hippocampus.
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.
authors.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.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhu
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China ; Dean's Office, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Oudong
authors.initials: O
authors.lastname: Xia
authors.affiliation: Hygiene Detection Center, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Han
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Shao
authors.affiliation: Traditional Chinese Medicine Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510305, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Jing
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fan
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Diao
authors.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.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Lv
authors.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.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Sun
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