Dataset Information

Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

ABSTRACT: Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: 60 adult C57BL/6J mice were randomly divided into four groups, including control group, CUMS group, Xiaoyaosan treatment group and fluoxetine treatment group. Mice in the control group and CUMS group received 0.5 mL physiological saline once a day by intragastric administration. Mice in two treatment groups received Xiaoyaosan (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. After 21 days of modeling with CUMS, the expression of apelin and APJ in hypothalamus were measured by real-time fluorescence quantitative PCR, western blot and immunohistochemical staining. The physical condition, body weight, food intake and behavior tests such as open field test, sucrose preference test and force swimming test were measured to evaluate depressive-like behaviors. Results: In this study, significant behavioral changes were found in CUMS-induced mice, meanwhile the expressions of apelin and APJ in the hypothalamus were changed after modeling. The body weight, food-intake and depressive-like behaviors in CUMS-induced mice could be improved by Xiaoyaosan treatment which is similar with the efficacy of fluoxetine, while the expressions of apelin and APJ in hypothalamus were modified by Xiaoyaosan. Conclusions: The data suggest that apelin-APJ system changes in the hypothalamus may be a target of depressive disorders, and the beneficial effects of Chinese compound prescription Xiaoyaosan on depressive-like behaviors may be mediated by the apelin-APJ system.

SUBMITTER: Yan Z

PROVIDER: S-EPMC6102542 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

Yan Zhiyi Z Jiao Haiyan H Ding Xiufang X Ma Qingyu Q Li Xiaojuan X Pan Qiuxia Q Wang Tingye T Hou Yajing Y Jiang Youming Y Liu Yueyun Y Chen Jiaxu J

Molecules (Basel, Switzerland) 20180503 5

Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: ...[more]

PMID: 29751542

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Project description:BackgroundAt present, the pathogenesis of depression is not fully understood, and nearly half of depression patients experience no obvious effects during treatment. This study aimed to establish a depression mouse model to explore the possible role of ferroptosis in the pathogenesis of depression, and observe the effects of Xiaoyaosan on PEBP1-GPX4-mediated ferroptosis in the hippocampus.MethodsForty-eight male C57BL/6 mice were randomly divided into a control group, CUMS group, Xiaoyaosan group and fluoxetine group, and the model was established by chronic unpredictable mild stress (CUMS) for a successive 6 weeks. The medication procedure was performed from the 4th to the 6th week of modeling. The behavioral evaluations were measured to evaluate depressive-like behaviors. The expressions of GPX4, FTH1, ACSL4 and COX2 were detected as ferroptosis-related indicators. Then, the total iron and ferrous content in the hippocampus were measured. The levels of PEBP1 and ERK1/2 were observed, and the expressions of GFAP and IBA1 were also detected to measure the functions of astrocytes and microglia in the hippocampus.ResultsEight herbs of Xiaoyaosan had 133 active ingredients which could regulate the 43 ferroptosis-related genes in depression. After 6 weeks of modeling, the data showed that mice in the CUMS group had obvious depressive-like behaviors, and medication with Xiaoyaosan or fluoxetine could significantly improve the behavioral changes. The expressions of GPX4, FTH1, ACSL4, COX2, PEBP1, ERK1/2, GFAP and IBA1 changed in the CUMS group mice, while the total iron and ferrous content also changed. Xiaoyaosan and fluoxetine had obvious curative effects that could significantly alleviate the above changes in the hippocampus.ConclusionOur results revealed that the activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs.

Dataset Information

Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

Publications

Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

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