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

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.

Keywords:

• depression
• immune homeostasis
• inflammation
• traditional Chinese medicine
• hippocampus

View correction statement:

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

Abbreviation

WTJD, Wenyang-tianjing-jieyu decoction; KYD, Kidney yang deficiency; CUMS, Chronic unpredictable mild stimulus; JAK2, Janus kinase 2; STAT3, Signal transducer and activator of transcription 3; TLR4, Toll-like receptor 4; TRAF6, Tumor necrosis factor receptor-associated factor 6; NF-κB, Nuclear transcription factor-κB; TCM, Traditional Chinese Medicine; RORγt, Retinoic acid receptor-related orphan receptor γ-t; FOXP3, Forkhead box protein P3; T-bet, T-box 21 transcription factor; GATA3, GATA binding protein 3; IL-, Interleukin-; TNF-α, Tumor necrosis factor-α; IFN-γ, Interferon-γ; TGF-β1, Transforming growth factor-β1.

Data Sharing Statement

The data that support the findings of this study are available upon request from the corresponding author, upon reasonable request.

Credit Authorship Contribution Statement

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Acknowledgments

Thanks to Home for Researchers (www.home-for-researchers.com) for the language improvements in this article.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

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].