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A classic famous prescription alleviates inflammation in CUMS model mice via modulating MYDGF/MAP4K4/NF-κB signaling pathway, verified through UPLC-HRMS and proteomics analysis

ABSTRACT: Major depressive disorder (MDD) has caused a heavy burden on society and affected over 350 million patients worldwide currently. However, there have been 30-50% MDD patients with non-response to antidepressants. Chronic unpredictable mild stress (CUMS) has been considered as a critical trigger factor for MDD, the pathological mechanism of which is strongly associated with stimulating inflammatory responses. Xiaoyaosan (XYS), as a classic famous prescription, has been proven effective for alleviating CUMS induced injury. Purpose: This study aimed to clarify the potential anti-inflammatory mechanisms of XYS treating CUMS model mice. Study design and methods: The therapeutic effects of XYS on the behavior and inflammatory indicators of CUMS model mice were determined. Ultra high performance liquid chromatography - High resolution mass spectrometry (UPLC-HRMS) was applied identify the compounds of XYS and proteomics analysis was utilized to explore the potential mechanism. Additionally, molecular docking and further in vivo experiments were conducted to verify the results of proteomics analysis. Results: The in vivo experiments confirmed XYS not only could significantly improve sucrose preference percentage and behavioral indicators of open field test, but also could decrease the serum levels of inflammatory indexes (CORT, hs-CRP, NFκB, FIB and Lp-PLA2) and inhibit the protein expressions of IL-6 and TNF-α in brain of CUMS model mice. Proteomics analysis presented that MAPK signaling pathway might be the important anti-inflammatory mechanism of XYS alleviating CUMS induced injury. UPLC-HRMS identify the compounds of XYS, which were taken into molecular docking to analysis the interaction between XYS and MYDGF, PKC, MAP4K4, P-p65, p65, P-IKBα, and IKBα. It was validated that XYS could exert regulatory effects on the MYDGF/MAP4K4/NF-κB signaling pathway in CUMS model mice. Conclusion: In conclusion, this study first demonstrated that XYS could alleviate inflammation in CUMS model mice via modulating MYDGF/MAP4K4/NF-κB signaling pathway.

ORGANISM(S): Mus Sp.

SUBMITTER: Xifei Yang

PROVIDER: PXD053391 | iProX | Tue Jun 25 00:00:00 BST 2024

REPOSITORIES: iProX

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A classic prescription alleviates inflammation in CUMS model mice via modulating MYDGF/MAP4K4/NF-κB signaling pathway, verified through UPLC-HRMS and proteomics analysis.

Huang Ruolan R Gong Shenglan S Xiong Bocheng B Yang Xifei X Chen Chongyang C Song Wei W Wu Ruodai R Yang Li L Yin Jia J Chen Mingtai M

Heliyon 20240714 14

<h4>Background</h4>Xiaoyaosan (XYS), a renowned classical traditional Chinese medicinal formula utilized in addressing major depressive disorder (MDD), has garnered significant acclaim for its remarkable efficacy in clinical application. The onset of major depressive disorder (MDD) often correlates with chronic unpredictable mild stress (CUMS), a pivotal instigating factor in its development.<b>Aim of the study</b>: This study aims to clarify the potential anti-inflammatory mechanisms of XYS in ...[more]

PMID: 39114061

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Dataset Information

A classic famous prescription alleviates inflammation in CUMS model mice via modulating MYDGF/MAP4K4/NF-κB signaling pathway, verified through UPLC-HRMS and proteomics analysis

Publications

A classic prescription alleviates inflammation in CUMS model mice via modulating MYDGF/MAP4K4/NF-κB signaling pathway, verified through UPLC-HRMS and proteomics analysis.

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