A classic prescription alleviates inflammation in CUMS model mice via modulating MYDGF/MAP4K4/NF-κB signaling pathway, verified through UPLC-HRMS and proteomics analysis
Ruolan Huang,
Shenglan Gong,
Bocheng Xiong,
Xifei Yang,
Chongyang Chen,
Wei Song,
Ruodai Wu,
Li Yang,
Jia Yin,
Mingtai Chen
Affiliations
Ruolan Huang
Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Shenzhen University General Hospital, Clinical Research Center for Neurological Diseases, Shenzhen University, Shenzhen, Guangdong, China
Shenglan Gong
Department of Cardiovascular Disease, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China; Sixth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
Bocheng Xiong
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020-2024), Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Xifei Yang
Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020-2024), Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
Chongyang Chen
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China
Wei Song
Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Ruodai Wu
Shenzhen University General Hospital, Clinical Research Center for Neurological Diseases, Shenzhen University, Shenzhen, Guangdong, China
Li Yang
Shenzhen University General Hospital, Clinical Research Center for Neurological Diseases, Shenzhen University, Shenzhen, Guangdong, China
Jia Yin
Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Corresponding author. Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Address No. 1023, South Shatai Road, Baiyun District, Guangzhou, Guangdong, China.
Mingtai Chen
Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China; Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao, China; Corresponding author. Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, No.1 Fuhua Road, Futian District, Shenzhen, Guangdong, China.
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.
