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

Autor: Ruolan Huang, Shenglan Gong, Bocheng Xiong, Xifei Yang, Chongyang Chen, Wei Song, Ruodai Wu, Li Yang, Jia Yin, Mingtai Chen
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Heliyon, Vol 10, Iss 14, Pp e34596- (2024)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2024.e34596
Popis: Background: 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.Aim of the study: This study aims to clarify the potential anti-inflammatory mechanisms of XYS in treating CUMS model mice. Materials and methods: Utilizing cutting-edge ultra high-performance liquid chromatography - high-resolution mass spectrometry (UPLC-HRMS), the active constituents of XYS were discerned, while employing proteomics analysis to delve into the potential mechanisms of its efficacy. Molecular docking studies, alongside subsequent in vivo experiments utilizing CUMS model mice, were conducted to corroborate the findings derived from the proteomics analysis. Results: In vivo experiments demonstrated that XYS not only markedly ameliorated behavioral markers but also attenuated serum inflammatory markers and suppressed IL-6 and TNF-α expression within the brains of CUMS model mice. Proteomics analysis suggested that the pivotal anti-inflammatory mechanism of XYS against CUMS-induced damage might involve modulation of the MAPK signaling pathway. Utilizing UPLC-HRMS, the active constituents of XYS were successfully identified, while molecular docking investigations explored interactions between XYS and MYDGF, PKC, MAP4K4, P-p65, p65, P-IKBα, and IKBα. The findings revealed XYS's regulatory influence on the MYDGF/MAP4K4/NF-κB signaling cascade. Conclusions: This study is the first to our knowledge to demonstrate that XYS can alleviate inflammation in CUMS model mice by modulating the MYDGF/MAP4K4/NF-κB signaling pathway.
Databáze: Directory of Open Access Journals