Gegen Qinlian Decoction treatment of asymptomatic hyperuricemia by targeting circadian immune function

Chinese Medicine

Research

Qiushuang Gao¹  Guannan Zhang²  Zheling Su³  Xuanqi Liu⁴  Xuchao Gu⁵  Xiaojun Wang⁵  Wenhao Wang⁵  Tao Wu⁵  Zhiyuan Sheng⁶  Maoqing Ye⁷ 

[1] China Pharmaceutical University, 210009, Nanjing, China;Department of Immunology, Key Laboratory of Immune Microenvironment and Disease, Nanjing Medical University, 211166, Nanjing, Jiangsu, China;Department of Nephrology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 200437, Shanghai, China;Department of Respiratory and Critical Medicine, Huadong Hospital Affiliated to Fudan University, 200040, Shanghai, China;Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No 221West Yan-An Road, 200040, Shanghai, China;Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, 200040, Shanghai, China;Department of Urology, Huadong Hospital Affiliated to Fudan University, 200040, Shanghai, China;Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, No 221 West Yan-An Road, 200040, Shanghai, China;Department of Cardiology, Huadong Hospital Affiliated to Fudan University, 200040, Shanghai, China;

关键词: Gegen Qinlian Decoction;    Hyperuricemia;    Circadian clock gene;    Innate lymphoid cells;   

DOI  :  10.1186/s13020-023-00775-z

 received in 2023-02-20, accepted in 2023-05-20,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe Gegen Qinlian Decoction (GGQLD) is a renowned traditional Chinese medicinal formula that has been used for centuries to effectively treat asymptomatic Hyperuricemia (HUA). This study aims to investigate the underlying mechanism of GGQLD's therapeutic effects on HUA.MethodsThe study enrolled a total of 25 healthy participants and 32 middle-aged and elderly individuals with asymptomatic HUA. All asymptomatic HUA participants were treated with GGQLD. Venous blood samples were collected from all participants to isolate peripheral blood mononuclear cells (PBMCs), which were then analyzed for biological profiles using flow cytometry. Network pharmacology analysis was utilized to identify the potential pathways involved in the therapeutic effects of GGQLD. Transcriptomic patterns of cultured proximal tubule epithelial cells (PTECs) were evaluated via bulk RNA-seq, and critical differentially expressed genes (DEGs) were identified and verified through ELISA. Molecular docking and molecular dynamics (MD) simulation were employed to investigate the potential compounds in GGQLD that may be involved in treating HUA.ResultsNetwork pharmacology analysis revealed that immune-related pathways might be involved in the therapeutic mechanism of GGQLD. RNA-seq analysis confirmed the involvement of innate lymphoid cell (ILC) development-related genes and clock genes. Polychromatic flow cytometric analysis demonstrated that GGQLD treatment reduced the proportion of ILC3s in total ILCs in asymptomatic HUA patients. ELISA results showed that GGQLD treatment reduced the levels of activating factors, such as ILC3-IL-18 and IL-1β, in the plasma of HUA patients. GGQLD was also found to regulate circadian clock gene expression in PBMCs to treat asymptomatic HUA. Furthermore, the interaction between 40 compounds in GGQLD and HDAC3 (Histone Deacetylase 3), NLRP3 (NOD-like receptor protein 3), RORA (RAR-related orphan receptor A), and REV-ERBα (nuclear receptor subfamily 1) revealed that GGQLD may regulate ILCs and clock genes to treat asymptomatic HUA.ConclusionsThe regulation of circadian clock gene expression and the proportion of ILC cells may be involved in the therapeutic effects of GGQLD on asymptomatic HUA patients.

【 授权许可】

CC BY   
© The Author(s) 2023

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