{
    "abstract": "Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM) without curative interventions currently. Huperzine A (Hup A), a natural alkaloid, has demonstrated significant hypoglycemic and anti-inflammatory effects. We aim to investigate the protective effects of Hup A on DN and explore the underlying mechanisms METHODS: We applied STZ induced diabetic rats as DN model and leveraged combination analysis of the transcriptome, metabolome, microbiome, and network pharmacology (NP). The total effect of Hup A on DN was detected (i.e. urine protein, renal tissue structure) and the differential genes were further verified at the level of diabetic patients, db/db mice and cells. Clinical data and small interfering RNA (siRNA)-Apoe were adopted.\nHup A alleviated kidney injury in DN rats. Transcriptomics data and Western blot indicated that the improvement in DN was primarily associated with Apoe and Apoc2. Additionally, metabolomics data demonstrated that DN-induced lipid metabolism disruption was regulated by Hup A, potentially involving sphingosine. Hup A also enriched microbial diversity and ameliorated DN-induced microbiota imbalance. Spearman's correlation analysis demonstrated significant associations among the transcriptome, metabolome, and microbiome. Apoe level was positively correlated with clinical biomarkers in DN patients. Si-Apoe also played protective role in podocytes. NP analysis also suggested that Hup A may treat DN by modulating lipid metabolism, microbial homeostasis, and apoptosis, further validating our findings.\nCollectively, we provide the first evidence of the therapeutic effect of Hup A on DN, indicating that Hup A is a potential drug for the prevention and treatment of DN.",
    "authors": [
        {
            "affiliation": "Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health,\u00a0Hangzhou,\u00a0Zhejiang,\u00a0China; Institute of Translational Medicine, Zhejiang University School of Medicine,\u00a0Hangzhou 310052,\u00a0China; School of TCM, Hunan University of Chinese Medicine,\u00a0China.",
            "firstname": "Xiangjun",
            "initials": "X",
            "lastname": "Chen"
        },
        {
            "affiliation": "Institute of Translational Medicine, Zhejiang University School of Medicine,\u00a0Hangzhou 310052,\u00a0China.",
            "firstname": "Ying",
            "initials": "Y",
            "lastname": "Zhang"
        },
        {
            "affiliation": "Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health,\u00a0Hangzhou,\u00a0Zhejiang,\u00a0China.",
            "firstname": "Zhongkai",
            "initials": "Z",
            "lastname": "Cao"
        },
        {
            "affiliation": "Hubei Normal University,\u00a0Huangshi 435002,\u00a0China.",
            "firstname": "Yue",
            "initials": "Y",
            "lastname": "Wang"
        },
        {
            "affiliation": "Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health,\u00a0Hangzhou,\u00a0Zhejiang,\u00a0China.",
            "firstname": "Mengqiu",
            "initials": "M",
            "lastname": "Liao"
        },
        {
            "affiliation": "Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health,\u00a0Hangzhou,\u00a0Zhejiang,\u00a0China.",
            "firstname": "Yuelin",
            "initials": "Y",
            "lastname": "Guan"
        },
        {
            "affiliation": "Department of Nephrology, Hangzhou TCM Hospital, Hangzhou, China.",
            "firstname": "Caifeng",
            "initials": "C",
            "lastname": "Zhu"
        },
        {
            "affiliation": "Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health,\u00a0Hangzhou,\u00a0Zhejiang,\u00a0China.",
            "firstname": "Wenmin",
            "initials": "W",
            "lastname": "Wang"
        },
        {
            "affiliation": "The First Clinical Medical College of Lanzhou University,\u00a0Lanzhou 730000,\u00a0China.",
            "firstname": "Wunan",
            "initials": "W",
            "lastname": "Huang"
        },
        {
            "affiliation": "Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health,\u00a0Hangzhou,\u00a0Zhejiang,\u00a0China.",
            "firstname": "Wei",
            "initials": "W",
            "lastname": "Li"
        },
        {
            "affiliation": "State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences,\u00a0China.",
            "firstname": "Yingping",
            "initials": "Y",
            "lastname": "Xiao"
        },
        {
            "affiliation": "Department of Nephrology, Hangzhou TCM Hospital, Hangzhou, China.",
            "firstname": "Yayu",
            "initials": "Y",
            "lastname": "Li"
        },
        {
            "affiliation": "Department of Nephrology, Hangzhou TCM Hospital, Hangzhou, China.",
            "firstname": "Jiazhen",
            "initials": "J",
            "lastname": "Yin"
        },
        {
            "affiliation": "State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University,\u00a0Beijing 100084,\u00a0China.",
            "firstname": "Yuhan",
            "initials": "Y",
            "lastname": "Ding"
        },
        {
            "affiliation": "School of TCM, Hunan University of Chinese Medicine,\u00a0China.",
            "firstname": "Qinghua",
            "initials": "Q",
            "lastname": "Peng"
        },
        {
            "affiliation": "Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health,\u00a0Hangzhou,\u00a0Zhejiang,\u00a0China. Electronic address: hulidan@zju.edu.cn.",
            "firstname": "Lidan",
            "initials": "L",
            "lastname": "Hu"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.",
    "doi": "10.1016/j.phrs.2024.107392",
    "journal": "Pharmacological research",
    "keywords": [
        "Diabetic nephropathy",
        "Hup A",
        "Metabolome",
        "Microbiome",
        "Network pharmacology",
        "Transcriptome"
    ],
    "methods": null,
    "publication_date": "2024-09-05",
    "pubmed_id": "39233057",
    "results": "Hup A alleviated kidney injury in DN rats. Transcriptomics data and Western blot indicated that the improvement in DN was primarily associated with Apoe and Apoc2. Additionally, metabolomics data demonstrated that DN-induced lipid metabolism disruption was regulated by Hup A, potentially involving sphingosine. Hup A also enriched microbial diversity and ameliorated DN-induced microbiota imbalance. Spearman's correlation analysis demonstrated significant associations among the transcriptome, metabolome, and microbiome. Apoe level was positively correlated with clinical biomarkers in DN patients. Si-Apoe also played protective role in podocytes. NP analysis also suggested that Hup A may treat DN by modulating lipid metabolism, microbial homeostasis, and apoptosis, further validating our findings.",
    "title": "Huperzine A targets Apolipoprotein E: A potential therapeutic drug for diabetic nephropathy based on omics analysis.",
    "xml": "<Element 'PubmedArticle' at 0x788505593c40>"
}