The antidepressant-like effects of Chaihu Shugan San: Dependent on the hippocampal BDNF-TrkB-ERK/Akt signaling activation in perimenopausal depression-like rats

Chen, Xueqin; Li, Cheng-Fu; Chen, Shujiao; Liang, Wenna; Wang, Miao; Wang, Shuangshuang; Dong, Shuqi; Yi, Long; Li, Candong

doi:10.1016/j.biopha.2018.04.035

Cited by 52 publications

(23 citation statements)

References 21 publications

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“…Previous findings have shown that paeoniflorin was the main constituent of Bai-Shao, which played an indispensable role in the antidepressant effect of CSS [24]. Previous studies have also demonstrated that CSS may cause antidepressive effects via regulation of the hippocampal BDNF-TrkB-ERK/Akt signaling pathway [25], while our research has shown that paeoniflorin can exert antidepressive and prokinetic effects similar to those found by CSS [3].…”

supporting

confidence: 66%

Antidepression and Prokinetic Effects of Paeoniflorin on Rats in the Forced Swimming Test via Polypharmacology

Xue

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Paeoniflorin, an organic compound extracted from the roots of the white peony (Paeonia lactiflora) plant, has previously been shown to exert antidepression and prokinetic effects. The traditional Chinese prescription Si-Ni-San, of which paeoniflorin is a constituent, is often used in treating depression and functional gastrointestinal disorders. The effectiveness of Si-Ni-San has been shown to be less effective in a paeoniflorin-deleted form. The present study further investigates whether paeoniflorin alone is as effective as herbal prescriptions in which the compound is a constituent, specifically any antidepressive and prokinetic effect on rats subjected to a forced swimming test (FST). The FST was used to establish the depression model. Sprague-Dawley rats were administrated with 10 mg/kg paeoniflorin by gastrogavage three times before the behavioral test and gastrointestinal motility tests, respectively. In antidepression studies, fluoxetine was used as the positive control. In order to determine the effect of paeoniflorin on the gastrointestinal movement, mosapride was used as the positive control. Plasma and hippocampus monoamine, hypothalamic-pituitary-adrenal axis, plasma brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), ghrelin, motilin, and hippocampus nitric oxide (NO) were assessed using an enzyme-linked immunosorbent assay (ELISA). Gastrointestinal (GI) motility was measured in vivo and in vitro. Rats subjected to FST showed decreased gastric emptying and intestinal transit in vivo, decreased plasma and hippocampus 5-hydroxytryptamine, norepinephrine, dopamine, ghrelin, motilin, and reduced plasma BDNF and SOD as well as increased plasma and hippocampus corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone, plasma MDA, and hippocampus NO. Paeoniflorin reversed these symptoms in a similar manner to fluoxetine and mosapride, respectively. In vitro, paeoniflorin can stimulate the jejunal contract of healthy rats dose-dependently. The results suggest that paeoniflorin can simultaneously exert antidepression and prokinetic effects via polypharmacology.

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supporting

confidence: 66%

Antidepression and Prokinetic Effects of Paeoniflorin on Rats in the Forced Swimming Test via Polypharmacology

Xue

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Although the antidepressant mechanism of different responses to CSGS treatment has been extensively investigated, these studies are mainly focused on hippocampal 5-HT receptor and brain-derived neurotrophic factor (BDNF) either at pre-or post-treated CSGS that correlates with therapeutic outcomes [16][17][18]. Herein, we paid more attention to the overall hippocampal metabolism after CGSG and the combined oral administration broad-spectrum antibiotic treatment and then conducted analyses by the UPLC-Q-TOF/MS-based metabolomics approach.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San

et al. 2020

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Accumulating evidence highlights the link between gut microbiota and depression. As an antidepressant herbal drug in clinic, Chaihu-Shu-Gan-San (CSGS) has also been used in China for the treatment of various gastrointestinal disorders. Therefore, we hypothesize that the gut microbiota might be involved in the effect of CSGS. Here, we investigated the antidepressant effects of CSGS against chronic variable stress (CVS)-induced depression rats with and without antibiotic treatment using 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled with time of flight mass spectrometry (UPLC-Q-TOF/MS) based metabolomics approaches. As a result, the prominent effects of CSGS against the depression-like behavioral disorder of CVS-induced rats were significantly weakened when the gut microbiota was changed after oral administration of the broad-spectrum antibiotic. The mediation of CSGS on hippocampal levels of serotonin (5-HT) and glutamic acid (Glu) was also receded with the antibiotic treatment. Further investigation on the diversity of microbiome indicated that the improvement effect of CSGS on gut microbiota dysbiosis—especially the phylum level of Firmicutes—was attenuated after the CSGS combined antibiotic treatment. Moreover, 3-hydroxypicolinic acid (H4) and inosine (H8) in the hippocampus were considered as important biomarkers for depression and are also associated with gut microbiota mediated CSGS efficacy. Taken together, our current study indicated that gut microbiota is a critical factor in the antidepressant effect of CSGS, which improve depression-related metabolic disturbance partly through gut microbiota.

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“…Recently, several studies have shown changes in the intracellular signalling pathways following longterm antidepressant treatment [48][49][50] . Most antidepressants activate CREB through the activation of Akt and ERK, and ultimately increase BDNF expression and alleviate depression 51 . BDNF belongs to the family of nerve growth factors and is involved in the development of the nervous system.…”

Section: Discussionmentioning

confidence: 99%

Creatine and taurine mixtures alleviate depressive-like behaviour in Drosophila melanogaster and mice via regulating Akt and ERK/BDNF pathways

Kim

Hong

Kim

et al. 2020

Sci Rep

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We investigated the antidepressant effect of creatine (CRE) and taurine (TAU) mixtures on behavioural changes and biomarkers in stress-induced depression in Drosophila melanogaster and a mouse model. Following CRE/TAU mixture administration in the Drosophila model, depression-like state induced by vibration, locomotion, climbing activity, and survival rate were measured. The normal stress (NS) group demonstrated decreased movement than the control (CON) group; movements in the CRE/TAUtreated group (particularly 0.15/0.5%) returned to the CON levels. Antidepressant effects of CRE/TAU mixtures were confirmed in a depressive mouse model induced by chronic mild stress. In behavioural assessments, movement and sucrose preference of the CRE/TAU group increased to a similar level as in the positive control group; hippocampal catecholamine and serotonin levels increased significantly. Stress-related hormones (adrenocorticotropic and corticotropin-releasing hormones) and inflammatory factors (IL-1β, IL-6, and TNF-α) increased in the NS group but significantly decreased in the CRE/TAU-treated group. Brain signalling protein expression ratio of phosphorylated protein kinase B (p-Akt)/Akt, phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK, and brain-derived neurotrophic factor (BDNF) significantly increased in the CRE/TAU-treated group. These results indicate that CRE/TAU-induced antidepressant effects are associated with increased behavioural patterns and downregulation of stress hormones and cytokines, mediated through Akt and ERK/BDNF pathways in vertebrate models. Depression, commonly known to render a person's mental state or physical activity incapacitated, is classified as one of the most dangerous diseases in modern society according to the World Health Organization (WHO), with a prevalence of 15-25% of the world's population 1,2. The etiology of depression remains unclear; however, biological, genetic, and social psychological factors are thought to interact with each other 3,4. Currently, most patients with depression are treated with synthetic drugs, including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, norepinephrine and dopamine reuptake blockers, and monoamine oxidase inhibitors 5. However, these chemically synthesised antidepressants have low reactivity and recovery rates and have side effects such as fatigue, sleep disorders, cognitive disorders, and sexual dysfunctions 6,7. Therefore, several studies have recently been undertaken owing to the increased demand for naturally derived antidepressants from medicinal plants and food-containing ingredients. The important physiological role of creatine (CRE) in depression has been confirmed in several clinical studies 8-10. Reportedly, there is a decrease in phosphocreatine in the brains of severely depressed patients 8. In particular, CRE supplements improve the mood of individuals with post-traumatic stress disorder, depression, fibromyalgia 9 , and therapy-resistant depres...

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The antidepressant-like effects of Chaihu Shugan San: Dependent on the hippocampal BDNF-TrkB-ERK/Akt signaling activation in perimenopausal depression-like rats

Cited by 52 publications

References 21 publications

Antidepression and Prokinetic Effects of Paeoniflorin on Rats in the Forced Swimming Test via Polypharmacology

Antidepression and Prokinetic Effects of Paeoniflorin on Rats in the Forced Swimming Test via Polypharmacology

Gut Microbiota Is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San

Creatine and taurine mixtures alleviate depressive-like behaviour in Drosophila melanogaster and mice via regulating Akt and ERK/BDNF pathways

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