{
  "abstract": "The gut microbiota plays a crucial role in the study of drug efficacy and metabolism. YZG-331 exhibits significant sedative and hypnotic effects. However, the oral bioavailability of YZG-331 in female mice remains low at 27.7%, and it exhibits instability in the gut microbiota, undergoing rapid metabolism, with the intestinal hydrolytic metabolite M2 identified as the characteristic metabolite. Both the underlying mechanisms of YZG-331 therapeutic effects on insomnia and its enzyme-mediated metabolic pathways involving the gut microbiota remain incompletely elucidated. In this study, we found that YZG-331 regulated the tryptophan metabolism and 5-HT production pathways by the gut microbiota. Specifically, YZG-331 increased the abundance of Lactobacillus and Muribaculaceae in the gut, with Lactobacillus reuteri playing a critical role in both the metabolic processes of YZG-331 and the biosynthesis of tryptophan-derived metabolites. YZG-331 enhanced the activation of the tetrahydrobiopterin (BH₄) cofactor system, which subsequently promoted tryptophan hydroxylase (TPH) activity, thereby enhancing 5-HT production. Furthermore, YZG-331 and M2 increased intestinal butyric acid levels, thereby promoting sleep regulation and supporting the restoration of the intestinal barrier. Overall, our study provided the first evidence highlighting the crucial role of the gut microbiota in the therapeutic mechanism and metabolic processing of YZG-331 in the treatment of insomnia.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.",
    "Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.",
    "Department of Allergy, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment on Allergic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hengtong Zuo"
    },
    {
      "affs": [
        0
      ],
      "name": "Qinglan Guo"
    },
    {
      "affs": [
        1
      ],
      "name": "Bin Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinyue Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Ru Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingyue Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianye Song"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingyu Jin"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiachun Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Hui Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Tiefeng Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Wanxia Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongmei Tu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lingyu Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifan Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiang Hui"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhihao Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Sheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianjun Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Jinlyu Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiangong Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Yan Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dqz530msvh0n8.bib",
  "cited_by": 0,
  "doi": "10.1016/j.apsb.2026.07.023",
  "fulltext_url": "https://europepmc.org/articles/PMC13712296",
  "id": "dqz530msvh0n8",
  "issns": [
    "2211-3835",
    "2211-3843"
  ],
  "landing_url": "https://europepmc.org/article/MED/42948711",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
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      "openalex",
      "1312|Gut microbiota and health"
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  "openalex": "W7169502397",
  "pdf_url": "https://europepmc.org/articles/PMC13712296?pdf=render",
  "pmcid": "PMC13712296",
  "pmid": "42948711",
  "published": "2026-07-17",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/dqz530msvh0n8.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:36Z",
      "native_id": "MED:42948711",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948711"
    },
    {
      "first_seen": "2026-10-31T12:22:54Z",
      "native_id": "PMC13712296",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.apsb.2026.07.023"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Gut microbiota and health",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Molecular mechanisms of YZG-331 ameliorated insomnia based on the gut microbiota-drug interaction.",
  "title_text": "Molecular mechanisms of YZG-331 ameliorated insomnia based on the gut microbiota-drug interaction.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:54Z",
  "url": "https://research.draconitic.com/paper/dqz530msvh0n8",
  "venue": "Acta pharmaceutica Sinica. B",
  "versions": []
}