{
  "abstract": "Soy isoflavones exhibit diverse health-promoting effects, including antioxidant and anti-inflammatory activities. However, these biological effects have largely been attributed to the modulation of cellular signaling pathways, whereas the influence of intestinal microbial metabolism on their direct radical-scavenging properties remains poorly understood. In this study, synthetic routes were established for the major intestinal bacterial metabolites daidzein and genistein, equol (Eq), dehydroequol (DEq), 5-hydroxyequol (5-OH-Eq), and, for the first time, 5-hydroxydehydroequol (5-OH-DEq), and their direct radical-scavenging activities, reaction mechanisms, radical-scavenging capacities, and DNA protective effects were systematically evaluated. Introduction of a C-ring double bond markedly enhanced direct radical-scavenging activity, whereas the parent isoflavones and their reduced metabolites exhibited little or no activity. Among the compounds examined, 5-OH-DEq exhibited the highest antioxidant activity, scavenging radicals predominantly through hydrogen atom transfer, with a second-order rate constant of 1.44 × 10³ M⁻¹ s⁻¹, exceeding that of Trolox and a radical-scavenging capacity of approximately three radical equivalents per molecule. Moreover, 5-OH-DEq protected plasmid DNA against radiation-induced oxidative damage. These findings demonstrate that intestinal microbial metabolism can function as a form of metabolic activation, converting dietary isoflavones into potent direct antioxidants. 5-OH-DEq was identified as a previously unexplored antioxidant metabolite and a promising lead scaffold for further development of next-generation phenolic antioxidants.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Organic and Medicinal Chemistry, Showa Medical University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan.",
    "Quantum RedOx Chemistry Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Chiba-shi 263-8555, Chiba, Japan.",
    "Institute for Open and Transdisciplinary Research Initiatives (OTRI), The University of Osaka, Suita 565-0871, Osaka, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sakurako Okada"
    },
    {
      "affs": [
        1
      ],
      "name": "Yoshimi Shoji"
    },
    {
      "affs": [
        0
      ],
      "name": "Masao Morita"
    },
    {
      "affs": [
        0
      ],
      "name": "Mika Hayashi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wakana Shimizu"
    },
    {
      "affs": [
        2
      ],
      "name": "Kei Ohkubo",
      "orcid": "0000-0001-8328-9249"
    },
    {
      "affs": [
        1
      ],
      "name": "Hiromu Ito"
    },
    {
      "affs": [
        1
      ],
      "name": "Ikuo Nakanishi",
      "orcid": "0000-0001-9204-0664"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kiyoshi Fukuhara",
      "orcid": "0000-0001-9677-7911"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cjah1a162sawr.bib",
  "cited_by": 0,
  "doi": "10.3390/antiox15101240",
  "fulltext_url": "https://europepmc.org/articles/PMC13700811",
  "id": "cjah1a162sawr",
  "issns": [
    "2076-3921"
  ],
  "landing_url": "https://europepmc.org/article/MED/42939813",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2734|Phytoestrogen effects and research"
    ]
  ],
  "openalex": "W7214335138",
  "pdf_url": "https://europepmc.org/articles/PMC13700811?pdf=render",
  "pmcid": "PMC13700811",
  "pmid": "42939813",
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cjah1a162sawr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42939813",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42939813"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Phytoestrogen effects and research",
      "subfield": "general"
    }
  ],
  "title": "Intestinal Microbial Metabolic Activation Converts Soy Isoflavones into Potent Direct Antioxidants: First Total Synthesis and Mechanistic Characterization of 5-Hydroxydehydroequol.",
  "title_text": "Intestinal Microbial Metabolic Activation Converts Soy Isoflavones into Potent Direct Antioxidants: First Total Synthesis and Mechanistic Characterization of 5-Hydroxydehydroequol.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/cjah1a162sawr",
  "venue": "Antioxidants (Basel, Switzerland)",
  "versions": []
}