The effect of deoxyschizandrin on chronic unpredictable mild stress–induced depression

Ma, Xin; Zhu, Zhenhua; Guo, Sheng; Duan, Jin‐Ao

doi:10.1002/bab.1893

Cited by 11 publications

(7 citation statements)

References 20 publications

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“…Our previous study demonstrated that leptin is essential for the effects of S. chinensis fruit extracts against MetS and NAFLD (Gu et al, 2020). Moreover, several studies have demonstrated that Schisandra chinensis , DS, and its analogues can alleviate diverse CNS diseases including depression, Parkinson's disease, Alzheimer's disease, etc (Ma et al, 2021; Yan et al, 2021; Zhang et al, 2018; Zhi et al, 2019). Therefore, we speculated that the effects of DS on anti‐MetS and satiety may be involved in hypothalamic activation of TGR5 and leptin signaling.…”

Section: Discussionmentioning

confidence: 99%

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Deoxyschizandrin ameliorates obesity and non‐alcoholic fatty liver disease: Involvement of dual Farnesyl X receptor/G protein‐coupled bile acid receptor 1 activation and leptin sensitization

Feng

Chen

et al. 2023

Phytotherapy Research

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Natural dual farnesyl X receptor (FXR)/G protein-coupled bile acid receptor 1 (TGR5) activators have received little attention in the management of metabolic diseases. Deoxyschizandrin (DS), a natural lignan, occurs in S. chinensis fruit and has potent hepatoprotective effects, whereas its protective roles and mechanisms against obesity and non-alcoholic fatty liver disease (NAFLD) are largely elusive. Here, we identified DS as a dual FXR/TGR5 agonist using luciferase reporter and cyclic adenosine monophosphate (cAMP) assays. DS was orally or intracerebroventricularly administrated to high-fat diet-induced obesity (DIO) mice, and methionine and cholinedeficient L-amino acid diet (MCD diet)-induced non-alcoholic steatohepatitis to evaluate its protective effects. Exogenous leptin treatment was employed to investigate the sensitization effect of DS on leptin. The molecular mechanism of DS was explored by Western blot, quantitative real-time PCR analysis, and ELISA. The results showed that DS activated FXR/TGR5 signaling and effectively reduced NAFLD in DIO and MCD diet-fed mice. DS countered obesity in DIO mice by promoting anorexia and energy expenditure and reversing leptin resistance, involving both peripheral and central TGR5 activation and leptin sensitization. Our findings indicate that DS may be a novel therapeutic approach for alleviating obesity and NAFLD through regulating FXR and TGR5 activities and leptin signaling.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, several studies have demonstrated that Schisandra chinensis, DS, and its analogues can alleviate diverse CNS diseases including depression, Parkinson's disease, Alzheimer's disease, etc (Ma et al, 2021;Yan et al, 2021;Zhang et al, 2018;Zhi et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Deoxyschizandrin ameliorates obesity and non‐alcoholic fatty liver disease: Involvement of dual Farnesyl X receptor/G protein‐coupled bile acid receptor 1 activation and leptin sensitization

Feng

Chen

et al. 2023

Phytotherapy Research

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“…Further, PSD 95 is widely involved in the onset and treatment of cognitive and emotional related mental diseases. 57,58 Many studies have shown that protein expression of SYN 1 and PSD 95 are decreased in the prefrontal cortex of patients with major depression. A decrease of presynaptic SYN 1 and postsynaptic PSD 95 in the hippocampus and prefrontal cortex due to chronic stress may lead to depressive behavior and a severe decline in cognitive function in rodents.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Wang

Zhang

et al. 2022

DDDT

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Background: There is growing evidence to suggest that ginsenoside Rd (GRd) has a therapeutic effect on depression, but the specific mechanisms behind its activity require further study. Objective: This study is designed to investigate the antidepressant-like effect and underlying mechanisms of GRd. Methods: In this study, the behavioral despair mouse model of depression and chronic unpredictable mild stress (CUMS) rat model of depression were established to explore the effects of GRd on depression-like behavior and its underlying mechanisms. Behavioral tests were used to evaluate the replication of animal models and depression-like behaviors. The hypoxia-inducible factor-1α (HIF-1α) blocker 2-methoxyestradiol (2-ME) was injected to determine the role of HIF-1α in the antidepressant-like effect of GRd. In addition, molecular biology techniques were used to determine the mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators, that is synapsin 1 (SYN 1) and postsynaptic density protein 95 (PSD 95). In silico binding interaction studies of GRd with focused target proteins were performed using molecular docking to predict the affinity and optimal binding mode between ligands and receptors. Results: Our data show that GRd significantly reversed depression-like behavior and promoted mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators. However, the antidepressant-like effect of GRd disappeared upon inhibition of HIF-1α expression following administration of 2-ME. Furthermore, molecular docking results showed that GRd possessed significant binding affinity for HIF-1α, VEGF, and VEGFR-2. Conclusion: Our results show that GRd exhibits significant antidepressant-like effect and that HIF-1α signaling pathway is a promising target for the treatment of depression.

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“…Target gene prediction of miRNAs was performed using the Encyclopedia of RNA Interactomes (ENCORI, http://starbase.sysu.edu.cn/index.php ) [ 34 ]. GO and KEGG pathway analyses were performed using WEB-based Gene SeT AnaLysis Toolkit (WebGestalt, http://www.webgestalt.org/ ) [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Immune and nonimmune mechanisms mediate the mental stress-induced tumor growth in a xenograft model of breast cancer

Liu

Zheng

et al. 2021

Cell Death Dis

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Excess mental stress may harm health, and even accelerate cancer initiation and progression. One fourth of breast cancer patients suffer mental stress including anxiety, sadness, or depression, which negatively affect prognosis and survival. However, the regulatory mechanism is yet to be determined. Herein, we applied unpredictable stress stimuli to the breast tumor-bearing mice to establish a xenograft model of breast cancer suffering mental stress, followed by behavioral tests, tumor growth tracking, immune analysis, miRNA screening, and tumor cell proliferation analysis as well. As a result, increased stress hormone levels in serum, decreased percentage of T and NK cells in both blood and tumor samples and accelerated tumor growth in vivo were observed in the mice exposed to mental stress. Promoted cell proliferation was observed in both primary tumor cells derived from the stressed mice and 4T1 breast cancer cells treated with stress hormone corticosterone. In addition, a subset of miRNAs including miR-326, 346, 493, 595, 615, and 665 were identified through a miRNA screening with downregulation in tumors of the stressed mice. CCND1 was identified as a common target gene of miR-346 and miR-493, the top two most significantly downregulated miRNAs by stress exposure. The stress-miRNA-CCND1 signaling regulation of the tumor cell proliferation was further validated in 4T1 cells treated with corticosterone in vitro. GO terms and KEGG pathways analyses on the target genes of miR-346 and miR-493 revealed their involvement in the regulation of human cancer and neuron system, indicating the importance of non-coding genome in mediating the mental stress-induced cancer regulation. In conclusion, this study not only explored immune and nonimmune mechanisms through which mental stress exposure contributes to tumor growth in breast cancer, but also suggested a new therapeutic strategy for cancer patients suffering mental stress.

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The effect of deoxyschizandrin on chronic unpredictable mild stress–induced depression

Cited by 11 publications

References 20 publications

Deoxyschizandrin ameliorates obesity and non‐alcoholic fatty liver disease: Involvement of dual Farnesyl X receptor/G protein‐coupled bile acid receptor 1 activation and leptin sensitization

Deoxyschizandrin ameliorates obesity and non‐alcoholic fatty liver disease: Involvement of dual Farnesyl X receptor/G protein‐coupled bile acid receptor 1 activation and leptin sensitization

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression

Immune and nonimmune mechanisms mediate the mental stress-induced tumor growth in a xenograft model of breast cancer

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