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      Wenyang-Tianjing-Jieyu Decoction Improves Depression Rats of Kidney Yang Deficiency Pattern by Regulating T Cell Homeostasis and Inflammation Level

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          Abstract

          Purpose

          Chronic inflammation is one of the key mechanisms of depression. Wenyang-Tianjin-Jie Decoction (WTJD) is an effective antidepressant found in the course of diagnosis and treatment, but the mechanism of therapeutic effect is not clear. The study aimed to evaluate the efficacy of WTJD in the kidney yang deficiency (KYD) type of depression rats and reveal its mechanisms.

          Materials and Methods

          We selected forty 6-week-old male Sprague-Dawley rats for the study. We established a KYD [Phellodendron amurense Rupr (Huangbai) solution oral gavage and 4°C environments; 8 weeks] type of depression (chronic unpredictable mild stimulus; 6 weeks) rat model first. After successful modeling, we used WTJD or fluoxetine on rats for 3 weeks. Then we evaluated the depression and KYD behavior. Finally, we observed the expression of key inflammatory factors and proteins in peripheral blood and hippocampus, and further investigated the immune balance of Th17/Treg and Th1/Th2 cells and the activity of their main regulatory pathways JAK2/STAT3 and TLR4/TRAF6/NF-κB.

          Results

          The imbalance of Th17/Treg and Th1/Th2 cells in rats were related to KYD and depressive symptoms. Through this study, we found that WTJD can inhibit the activity of JAK2/STAT3 and TLR4/TRAF6/NF-κB pathways, balance Th17/Treg and Th1/Th2 cell homeostasis, regulate the levels of inflammatory factors in the hippocampus and peripheral blood, and reverse KYD and depression.

          Conclusion

          This study confirmed that WTJD had a reliable effect on depression rats with KYD, and its mechanism was to regulate the immune homeostasis of hippocampal T cells and related inflammatory factors to improve KYD and depression symptoms in rats.

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          Most cited references69

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          Depression

          Major depression is a common illness that severely limits psychosocial functioning and diminishes quality of life. In 2008, WHO ranked major depression as the third cause of burden of disease worldwide and projected that the disease will rank first by 2030.1 In practice, its detection, diagnosis, and management often pose challenges for clinicians because of its various presentations, unpredictable course and prognosis, and variable response to treatment.
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            Th17 and regulatory T cell balance in autoimmune and inflammatory diseases.

            This review focuses on the biology of T helper 17 (Th17) and regulatory T (Treg) cells and their role in inflammatory diseases, such as rheumatoid arthritis. Th17 cells represent a pro-inflammatory subset whereas Treg cells have an antagonist effect. Their developmental pathways are reciprocally interconnected and there is an important plasticity between Th17 and Treg cells. These features implicate that the Th17/Treg balance plays a major role in the development and the disease outcomes of animal model and human autoimmune/inflammatory diseases. During these diseases, this balance is disturbed and this promotes the maintenance of inflammation. Targeting the Th17/Treg imbalance can be performed at different levels such as inhibition of pro-inflammatory cytokines and their receptors, of pathogenic cells or their specific signaling pathways. Conversely, direct effects include administration or induction of protective cells, or stimulation of their specific pathways. Several clinical trials are underway and some positive results have been obtained. Copyright © 2014 Elsevier B.V. All rights reserved.
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              The Balance of Th17 versus Treg Cells in Autoimmunity

              T helper type 17 (Th17) cells and pTreg cells, which share a common precursor cell (the naïve CD4 T cell), require a common tumor growth factor (TGF)-β signal for initial differentiation. However, terminally differentiated cells fulfill opposite functions: Th17 cells cause autoimmunity and inflammation, whereas Treg cells inhibit these phenomena and maintain immune homeostasis. Thus, unraveling the mechanisms that affect the Th17/Treg cell balance is critical if we are to better understand autoimmunity and tolerance. Recent studies have identified many factors that influence this balance; these factors range from signaling pathways triggered by T cell receptors, costimulatory receptors, and cytokines, to various metabolic pathways and the intestinal microbiota. This review article summarizes recent advances in our understanding of the Th17/Treg balance and its implications with respect to autoimmune disease.
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                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatr Dis Treat
                ndt
                Neuropsychiatric Disease and Treatment
                Dove
                1176-6328
                1178-2021
                22 March 2024
                2024
                : 20
                : 631-647
                Affiliations
                [1 ]Basic Medical College, Chengdu University of Traditional Chinese Medicine , Chengdu, People’s Republic of China
                Author notes
                Correspondence: Weihong Li, Basic Medical College, Chengdu University of Traditional Chinese Medicine , Chengdu, Sichuan Province, 610000, People’s Republic of China, Tel/Fax +8613882014290, Email lwh@cdutcm.edu.cn
                Author information
                http://orcid.org/0000-0002-7775-1342
                Article
                445636
                10.2147/NDT.S445636
                10966763
                38545129
                770f1d9b-bbb5-4796-bf66-61ffee7ca2f6
                © 2024 Zhang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 October 2023
                : 11 March 2024
                Page count
                Figures: 7, Tables: 1, References: 70, Pages: 17
                Funding
                Funded by: the National Key Research and Development Program of China;
                Funded by: the National Natural Science Foundation of China;
                Funded by: the Sichuan Science and Technology Program;
                This work was supported by the National Key Research and Development Program of China [grant number 2017YFC1703304], the National Natural Science Foundation of China [grant number 81873204], the Sichuan Science and Technology Program [grant number 2021YFS0040].
                Categories
                Original Research

                Neurology
                depression,immune homeostasis,inflammation,traditional chinese medicine,hippocampus
                Neurology
                depression, immune homeostasis, inflammation, traditional chinese medicine, hippocampus

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