{
    "abstract": "This study aimed to explore the main chemical components of Jiangniaosuan Formula (JNSF), the therapeutic effect of JNSF on hyperuricemia (HUA) mice, and the underlying mechanism by which JNSF inhibits renal tubular epithelial cell apoptosis.\nUltra Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry (UPLC-Q-TOF-MS) was used to analyze the chemical composition of JNSF and its serum metabolites. Network pharmacology was performed to predict the potential target genes and pathways. In vitro and in vivo models were established to verify the lower serum uric acid (SUA) and renal protective effects.\nUPLC-Q-TOF-MS identified 61 chemical compounds in JNSF and 56 metabolites in serum after oral administration. Network pharmacology suggested that Hypoxia-Inducible Factor 1-Alpha (HIF-1\u03b1), Cysteine-dependent Aspartate-specific Protease-3 (Caspase-3) and B-cell Lymphoma 2 (Bcl-2) might be the therapeutic targets of JNSF for the HUA treatment and JNSF may exert the therapeutic effect on uric acid nephropathy (UAN) through regulating HIF-1\u03b1 signaling pathway and apoptosis pathway. In vivo experiments showed that JNSF could reduce SUA, protect renal function and tubular function, alleviate renal interstitial edema and fibrosis, reduce the expression of Reactive Oxygen Species (ROS), HIF-1\u03b1 and Enhancer of Zeste Homolog 2 (EZH2), and inhibit cell apoptosis in HUA mice. In vitro experiments demonstrated that JNSF reversed apoptosis induced by EZH2 overexpression plasmid. Furthermore, we found that UA could promote the binding of HIF-1\u03b1 to EZH2 protein and its promoter, enhancing EZH2 transcription, suggesting that JNSF could alleviate the progression of HUA-induced kidney injury by inhibiting the activation of ROS/HIF-1\u03b1/EZH2 pathway.\nJNSF may attenuate HUA-induced renal injury by inhibiting apoptosis through the downregulation of ROS/HIF-1\u03b1/EZH2 pathway.",
    "authors": [
        {
            "affiliation": "Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China; TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, China.",
            "firstname": "Jiabao",
            "initials": "J",
            "lastname": "Zhou"
        },
        {
            "affiliation": "Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China; TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, China.",
            "firstname": "Feng",
            "initials": "F",
            "lastname": "Yang"
        },
        {
            "affiliation": "Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China; TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, China.",
            "firstname": "Xuming",
            "initials": "X",
            "lastname": "Zhang"
        },
        {
            "affiliation": "Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China; TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, China.",
            "firstname": "Chuanxu",
            "initials": "C",
            "lastname": "Wang"
        },
        {
            "affiliation": "Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China; TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, China.",
            "firstname": "Zhiyuan",
            "initials": "Z",
            "lastname": "Wu"
        },
        {
            "affiliation": "Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, China; TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, China. Electronic address: jiandong.gao@shutcm.edu.cn.",
            "firstname": "Jiandong",
            "initials": "J",
            "lastname": "Gao"
        }
    ],
    "conclusions": "JNSF may attenuate HUA-induced renal injury by inhibiting apoptosis through the downregulation of ROS/HIF-1\u03b1/EZH2 pathway.",
    "copyrights": "Copyright \u00a9 2025 The Authors. Published by Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.bioorg.2025.108363",
    "journal": "Bioorganic chemistry",
    "keywords": [
        "Apoptosis",
        "Hyperuricemia",
        "Jiangniaosuan formula (JNSF)",
        "Network pharmacology",
        "ROS/HIF-1\u03b1/EZH2 pathway",
        "Renal injury"
    ],
    "methods": null,
    "publication_date": "2025-03-16",
    "pubmed_id": "40088688",
    "results": "UPLC-Q-TOF-MS identified 61 chemical compounds in JNSF and 56 metabolites in serum after oral administration. Network pharmacology suggested that Hypoxia-Inducible Factor 1-Alpha (HIF-1\u03b1), Cysteine-dependent Aspartate-specific Protease-3 (Caspase-3) and B-cell Lymphoma 2 (Bcl-2) might be the therapeutic targets of JNSF for the HUA treatment and JNSF may exert the therapeutic effect on uric acid nephropathy (UAN) through regulating HIF-1\u03b1 signaling pathway and apoptosis pathway. In vivo experiments showed that JNSF could reduce SUA, protect renal function and tubular function, alleviate renal interstitial edema and fibrosis, reduce the expression of Reactive Oxygen Species (ROS), HIF-1\u03b1 and Enhancer of Zeste Homolog 2 (EZH2), and inhibit cell apoptosis in HUA mice. In vitro experiments demonstrated that JNSF reversed apoptosis induced by EZH2 overexpression plasmid. Furthermore, we found that UA could promote the binding of HIF-1\u03b1 to EZH2 protein and its promoter, enhancing EZH2 transcription, suggesting that JNSF could alleviate the progression of HUA-induced kidney injury by inhibiting the activation of ROS/HIF-1\u03b1/EZH2 pathway.",
    "title": "Jiangniaosuan formula inhibits hyperuricemia-induced apoptosis of renal tubular epithelial cells via ROS/HIF-1\u03b1/EZH2 pathway: A network pharmacology analysis and experimental validation.",
    "xml": "<Element 'PubmedArticle' at 0x7885065fd170>"
}