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

Yan, Zhonghua; Hu, Jiao; Ding, Xin; Ma, Qingyu; Li, Xiaojuan; Pan, Qiuxia; Wang, Tingye; Hou, Yajing; Jiang, You-Ming; Liu, Yueyun; Chen, Jiaxu

doi:10.3390/molecules23051073

Cited by 40 publications

(30 citation statements)

References 59 publications

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“…Moreover, the HPA axis and brain-derived neurotrophic factor (BDNF) have also been widely studied in the context of pathogenesis and treatment of depressive disorders (Jiang et al, 2016). Previous studies have demonstrated that XYS could reverse chronic stress-induced anxiety-like symptoms by regulating the apelin-APJ system in the hypothalamus and activity of the HPA axis (Yan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

An Integrated Pharmacology-Based Analysis for Antidepressant Mechanism of Chinese Herbal Formula Xiao-Yao-San

et al. 2020

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Clinical studies and basic science experiments have widely demonstrated the antidepressant and anxiolytic effects of the herbal formula Xiao-Yao-San (XYS). However, the system mechanism of these effects has not been fully characterized. The present study conducted a comprehensive network pharmacological analysis of XYS and sorted all pharmacologically active components (149) through the TCMSP webserver. Then, all potential molecular targets (449) were predicted, of which there were 99 genes clearly related to depression. To further investigate the mechanism of antidepressant effects of XYS, a compound-depression targets (C-DTs) network was constructed, and Gene Ontology (GO) functional and KEGG pathway enrichment analyses were performed for the 99 targets. Enrichment results revealed that XYS could regulate multiple aspects of depression through these targets, related to metabolism, neuroendocrine function, and neuroimmunity. Prediction and analysis of protein-protein interactions resulted in selection of three hub genes (AKT1, TP53, and VEGFA). In addition, a total of seven ingredients from XYS could act on these hub genes and they were identified through ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS), including paeoniflorin, quercetin, luteolin, acacetin, aloe-emodin, Glyasperin C, kaempferol. Hereafter, we investigated the effects of paeoniflorin and its predicted target, the results suggest that it can reverse the neurotoxicity produced by CORT and could be a neuroprotective effect by promoting the phosphorylation of Akt. Overall, our research revealed the complicated antidepressant mechanism of XYS, and also provided a rational strategy for revealing the complex composition and function of Chinese herbal formula.

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Section: Discussionmentioning

confidence: 99%

An Integrated Pharmacology-Based Analysis for Antidepressant Mechanism of Chinese Herbal Formula Xiao-Yao-San

et al. 2020

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“…Exposure to CUMS, which utilizes a battery of different stressors over a time course of several weeks, relatively consistently led to decreases in food intake (Patterson et al, 2010;Yao et al, 2016;He et al, 2018;Yan et al, 2018) and body weight in mice and rats (Forbes et al, 1996;Harris et al, 1997;Patterson et al, 2010;Lopez Lopez et al, 2018;Simas et al, 2018;Yan et al, 2018;Li et al, 2019;Yun et al, 2020). A few studies reported decreases in body weight or body weight gain, while food intake was not significantly altered (Harris et al, 1997;Lopez Lopez et al, 2018;Simas et al, 2018).…”

Section: Effects Of Stress On Food Intake and Body Weight In Rodents mentioning

confidence: 99%

“…In line with this notion, several of the previously mentioned studies also evaluated sucrose or saccharine preference. Some found no differences (Forbes et al, 1996;Harris et al, 1997;Yun et al, 2020), but in several studies CUMS exposure led to reduced sucrose or saccharine intake (Yao et al, 2016;Huang et al, 2017;He et al, 2018;Yan et al, 2018), which may reflect stress-induced anhedonia.…”

Section: Effects Of Stress On Food Intake and Body Weight In Rodents mentioning

confidence: 99%

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

Fritz

Singewald

Bundel

2020

Front. Synaptic Neurosci.

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Ghrelin is a peptide hormone released by specialized X/A cells in the stomach and activated by acylation. Following its secretion, it binds to ghrelin receptors in the periphery to regulate energy balance, but it also acts on the central nervous system where it induces a potent orexigenic effect. Several types of stressors have been shown to stimulate ghrelin release in rodents, including nutritional stressors like food deprivation, but also physical and psychological stressors such as foot shocks, social defeat, forced immobilization or chronic unpredictable mild stress. The mechanism through which these stressors drive ghrelin release from the stomach lining remains unknown and, to date, the resulting consequences of ghrelin release for stress coping remain poorly understood. Indeed, ghrelin has been proposed to act as a stress hormone that reduces fear, anxiety-and depression-like behaviors in rodents but some studies suggest that ghrelin may-in contrast-promote such behaviors. In this review, we aim to provide a comprehensive overview of the literature on the role of the ghrelin system in stress coping. We discuss whether ghrelin release is more than a byproduct of disrupted energy homeostasis following stress exposure. Furthermore, we explore the notion that ghrelin receptor signaling in the brain may have effects independent of circulating ghrelin and in what way this might influence stress coping in rodents. Finally, we examine how the ghrelin system could be utilized as a therapeutic avenue in stressrelated psychiatric disorders (with a focus on anxiety-and trauma-related disorders), for example to develop novel biomarkers for a better diagnosis or new interventions to tackle relapse or treatment resistance in patients.

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“…APJ and apelin are distributed in the hypothalamic nuclei, especially in the supraoptic nucleus and paraventricular nucleus (PVN; De Mota et al, ; Pope, Roberts, Lolait, & O'Carroll, ). Studies have suggested that the apelin/APJ system plays a role in regulating the activity of the hypothalamic–pituitary–adrenal axis (Kagiyama et al, ; Yan et al, ). Moreover, the apelin/APJ system affects behavior and physiology in the brain.…”

Section: Agonists Of Apjmentioning

confidence: 99%

Targeting drugs to APJ receptor: From signaling to pathophysiological effects

Huang

Chen

et al. 2018

Journal Cellular Physiology

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G-protein-coupled receptors (GPCRs) are recognized as the largest protein receptor superfamily, which are widely distributed in various tissues and organs. In addition, GPCRs are involved in many physiological and pathological longitudinal responses. Studies have indicated that putative receptor protein related to AT1 (APJ receptor) is an orphan GPCRs until its endogenous ligand apelin is found. Recently, Elabela, a new APJ receptor endogenous ligand was also found. Some evidence showed that the APJ receptor is distributed in the central nervous and cardiovascular systems. Moreover, the APJ receptor and its ligand are involved in many physiological functions and pathophysiological effects, making it a promising drug target for future treatment of diseases such as ischemic heart disease, hypertension, heart failure, and others. Although APJ is closely associated with many diseases, there are no drugs that can activate or inhibit APJ directly. In the current review, we try our best to summarize all agonists and antagonists targeting APJ, including peptides and small molecules. Given the role of apelin/APJ and Elabela/APJ in cardiovascular and other diseases, we believe that the combination of these agonists and antagonists with apelin and Elabela will play a corresponding role in various pathophysiological effects with further development of research.

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

Cited by 40 publications

References 59 publications

An Integrated Pharmacology-Based Analysis for Antidepressant Mechanism of Chinese Herbal Formula Xiao-Yao-San

An Integrated Pharmacology-Based Analysis for Antidepressant Mechanism of Chinese Herbal Formula Xiao-Yao-San

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

Targeting drugs to APJ receptor: From signaling to pathophysiological effects

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