{
  "abstract": "Context: Current anti-inflammatory drugs often cause significant adverse effects, underscoring the need for safer alternatives. Natural products with rare and distinctive scaffolds represent a promising source of leads for discovering new anti-inflammatory agents.\n\nObjective: This study aimed to find anti-inflammatory flavonoid-sesquiterpenoid hybrids from Syzygium simile (Myrtaceae), and to clarify the structural-activity relationship underlying their inhibition of biomarkers in activated human neutrophils.\n\nMaterials and methods: A range of chromatographic techniques was sequentially applied to isolate pure compounds, the structures of which were elucidated by spectroscopic and spectrometric analyses. Anti-inflammatory activities were evaluated in fMLP/CB-induced human neutrophils by measuring inhibitory effects on superoxide anion generation and elastase release.\n\nResults: Twenty-two flavonoid-sesquiterpenoid hybrids, including thirteen previously undescribed structures, were isolated from S. simile leaves, comprising five flavonoid scaffolds (types I–V) and five sesquiterpenoid moieties (germacrene-, cubebene-, oplopene-, cadinene-, and copaene-types) generated via distinctive electron transfer-mediated biosynthesis. Most compounds potently inhibited superoxide anion generation and elastase release, with IC50 values up to 32-fold lower than that of the positive control, without exhibiting cytotoxicity.\n\nDiscussion and Conclusion: Structure-activity relationship analysis revealed that the combination of a type I flavonoid and a germacrene-type sesquiterpenoid skeleton, integrated through an rA-type ring fusion, represents the optimal pharmacophore. The lead compound, simisyzygin C (3), achieved nanomolar potency with IC50 values of 0.04 μM (superoxide anion) and 0.16 μM (elastase release). These findings identify flavonoid-sesquiterpenoid hybrids as a structurally distinctive class of anti-inflammatory natural products, providing a structural basis for lead optimization.",
  "abstract_shown": true,
  "affiliations": [
    "School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan",
    "Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan",
    "Graduate Institute of Health Industry Technology and Center for Drug Research and Development, Chang Gung University of Science and Technology, Taoyuan, Taiwan",
    "Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, Chinese Medicine Research Center, China Medical University, Taichung, Taiwan",
    "Department of Biotechnology, Asia University, Taichung, Taiwan",
    "Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan",
    "Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan",
    "Department of Pharmacy, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yu-Chun Lin",
      "orcid": "0009-0008-5749-6082"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ho-Cheng Wu",
      "orcid": "0000-0002-6648-6010"
    },
    {
      "affs": [
        2
      ],
      "name": "Tsong-Long Hwang",
      "orcid": "0000-0002-5780-3977"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Yueh-Hsiung Kuo",
      "orcid": "0000-0001-5935-6755"
    },
    {
      "affs": [
        5
      ],
      "name": "Chu-Hung Lin"
    },
    {
      "affs": [
        0,
        1,
        6,
        7
      ],
      "name": "Horng-Huey Ko",
      "orcid": "0000-0003-4203-0200"
    },
    {
      "affs": [
        0,
        1,
        6
      ],
      "name": "Hsun-Shuo Chang",
      "orcid": "0000-0003-2745-139X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7bm6r2mg0kthb.bib",
  "cited_by": 0,
  "doi": "10.1080/13880209.2026.2746239",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13717781/",
  "id": "7bm6r2mg0kthb",
  "issns": [
    "1388-0209",
    "1744-5116"
  ],
  "landing_url": "https://doi.org/10.1080/13880209.2026.2746239",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1110|Phytochemistry and Biological Activities"
    ]
  ],
  "openalex": "W7224105827",
  "pdf_url": "https://www.tandfonline.com/doi/pdf/10.1080/13880209.2026.2746239?needAccess=true",
  "pmcid": "PMC13717781",
  "pmid": "42947618",
  "published": "2026-10-28",
  "publisher": "Taylor & Francis",
  "ris": "https://research.draconitic.com/paper/7bm6r2mg0kthb.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:22:02Z",
      "native_id": "PMC13717781",
      "source": "pmc",
      "url": "https://doi.org/10.1080/13880209.2026.2746239"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1110|Phytochemistry and Biological Activities",
      "subfield": "plant-biology"
    }
  ],
  "title": "Discovery of potent anti-inflammatory flavonoid-sesquiterpenoid hybrids from Syzygium simile: Structure–activity relationships and nanomolar inhibition of human neutrophil activation",
  "title_text": "Discovery of potent anti-inflammatory flavonoid-sesquiterpenoid hybrids from Syzygium simile: Structure–activity relationships and nanomolar inhibition of human neutrophil activation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:02Z",
  "url": "https://research.draconitic.com/paper/7bm6r2mg0kthb",
  "venue": "Pharmaceutical Biology",
  "versions": []
}