{
    "abstract": "Geniposide (GE) has potential efficacy in treating ulcerative colitis (UC). However, its reactivity can be affected by rapid degradation after oral administration. Furthermore, increasing oral doses may lead to hepatotoxicity. Thus, We used enema administration, characterized by smaller dose and higher localized concentration in the lesion, to improve the above situation.\nWe aimed to confirm that enema administration is a better modality than oral administration for GE against UC and to explore its mechanism.\nWe established UC mouse model, monitoring Disease Activity Index (DAI), inflammatory cytokines levels, and histopathology. Macrogenomics and bile acid (BAs) metabolomics analysed the major intestinal flora and BAs. Simultaneouslly, we conducted quantitative proteomics analysis and screened core proteins and pathway. In vitro validation was taken by qPCR, immunofluorescence and immunoblotting experiments.\nGE via enema alleviate UC by inhibiting inflammatory factor production through downregulating S100A8/S100A9/NF-\u03baB pathway. Analysis of the intestinal flora and BAs revealed that the enhanced abundance of Lachnospiraceae, which improves the ratio of primary to secondary BAs, and the reduced abundance of Provocaceae, which increases intestinal permeability and promotes inflammation, favored the restoration of the intestinal barrier. In addition, in vitro experiments confirmed that the key BA metabolites (mainly UDCA, DCA, and LCA) stimulated TGR5 signal to inhibit the assembly of the NLRP3 inflammasome and alleviated inflammation.\nWe firstly confirmed that GE alleviates UC via the enema route in a better manner than the oral route, through enhancing the intestinal barrier, restoring intestinal flora and BAs homeostasis, and inhibiting inflammatory injury. This study initially revealed that GE can alleviate UC through elevating UDCA, DCA, and LCA levels at the colonic site to activate TGR5 receptor for inhibiting the NLRP3 inflammasome, in addition to downregulating the S100A8/S100A9/-TLR4-NF-\u03baB pathway related inflammatory response directly. The evidences offer a promising strategy and profround meaning for UC treatment.",
    "authors": [
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.",
            "firstname": "Bao-Xin",
            "initials": "BX",
            "lastname": "Zheng"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: yyi@icmm.ac.cn.",
            "firstname": "Yan",
            "initials": "Y",
            "lastname": "Yi"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: xwwang@icmm.ac.cn.",
            "firstname": "Xing-Wen",
            "initials": "XW",
            "lastname": "Wang"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: cyli@icmm.ac.cn.",
            "firstname": "Chun-Ying",
            "initials": "CY",
            "lastname": "Li"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: yzhao@icmm.ac.cn.",
            "firstname": "Yong",
            "initials": "Y",
            "lastname": "Zhao"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: jztian@icmm.ac.cn.",
            "firstname": "Jing-Zhuo",
            "initials": "JZ",
            "lastname": "Tian"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: lmwang@icmm.ac.cn.",
            "firstname": "Lian-Mei",
            "initials": "LM",
            "lastname": "Wang"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: jyhan@icmm.ac.cn.",
            "firstname": "Jia-Yin",
            "initials": "JY",
            "lastname": "Han"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: cpan@icmm.ac.cn.",
            "firstname": "Chen",
            "initials": "C",
            "lastname": "Pan"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: syliu@icmm.ac.cn.",
            "firstname": "Su-Yan",
            "initials": "SY",
            "lastname": "Liu"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: cyliu@icmm.ac.cn.",
            "firstname": "Chen-Yue",
            "initials": "CY",
            "lastname": "Liu"
        },
        {
            "affiliation": "Chongqing University Of Chinese Medicine, Chongging 400060, China. Electronic address: 1696505488@qq.com.",
            "firstname": "Sha-Sha",
            "initials": "SS",
            "lastname": "Qin"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: tangxuan052@sina.com.",
            "firstname": "Xuan",
            "initials": "X",
            "lastname": "Tang"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.",
            "firstname": "Mei-Ting",
            "initials": "MT",
            "lastname": "Liu"
        },
        {
            "affiliation": "State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: ahliang@icmm.ac.cn.",
            "firstname": "Ai-Hua",
            "initials": "AH",
            "lastname": "Liang"
        }
    ],
    "conclusions": "We firstly confirmed that GE alleviates UC via the enema route in a better manner than the oral route, through enhancing the intestinal barrier, restoring intestinal flora and BAs homeostasis, and inhibiting inflammatory injury. This study initially revealed that GE can alleviate UC through elevating UDCA, DCA, and LCA levels at the colonic site to activate TGR5 receptor for inhibiting the NLRP3 inflammasome, in addition to downregulating the S100A8/S100A9/-TLR4-NF-\u03baB pathway related inflammatory response directly. The evidences offer a promising strategy and profround meaning for UC treatment.",
    "copyrights": "Copyright \u00a9 2025. Published by Elsevier GmbH.",
    "doi": "10.1016/j.phymed.2025.156791",
    "journal": "Phytomedicine : international journal of phytotherapy and phytopharmacology",
    "keywords": [
        "Bile acid pool",
        "Colitis",
        "Geniposide",
        "Gut microbiota",
        "Immune homeostasis",
        "Intestinal barrier"
    ],
    "methods": null,
    "publication_date": "2025-04-26",
    "pubmed_id": "40279965",
    "results": "GE via enema alleviate UC by inhibiting inflammatory factor production through downregulating S100A8/S100A9/NF-\u03baB pathway. Analysis of the intestinal flora and BAs revealed that the enhanced abundance of Lachnospiraceae, which improves the ratio of primary to secondary BAs, and the reduced abundance of Provocaceae, which increases intestinal permeability and promotes inflammation, favored the restoration of the intestinal barrier. In addition, in vitro experiments confirmed that the key BA metabolites (mainly UDCA, DCA, and LCA) stimulated TGR5 signal to inhibit the assembly of the NLRP3 inflammasome and alleviated inflammation.",
    "title": "Geniposide via enema alleviates colitis by modulating intestinal flora and bile acid metabolites, inhibiting S100A8/S100A9/NF-\u03baB, and promoting TGR5 inhibition of NLRP3 inflammasome.",
    "xml": "<Element 'PubmedArticle' at 0x788501d69f30>"
}