{
  "abstract": "Background: Calcium overload is a central pathological factor in cardiovascular disorders, including arrhythmia and myocardial injury. Recent studies suggest that ginsenoside metabolites may alleviate calcium overload; however, the principal active metabolite and its direct molecular target remain unclear. Methods: This study systematically screened the active components of enzymatically hydrolyzed total ginsenosides by integrating UPLC-Q/TOF-MS, principal component analysis, and calcium antagonistic activity assays. An alkynylated probe of the key active component was then synthesized for target identification using chemical biology approaches. Molecular biology methods were used to investigate the binding mechanisms. Rat models of arrhythmia and myocardial oxidative injury were further used to evaluate its pharmacological effects in vivo and to examine the associated signaling pathway. Results: The study revealed that the calcium antagonistic activity of ginsenosides was closely associated with secondary saponins, particularly ginsenoside CK (G-CK). CaMKII was identified as a key target through which G-CK alleviates calcium overload. G-CK bound to CaMKII and suppressed its autophosphorylation. Molecular biology experiments collectively supported an ATP-competitive mode of CaMKII inhibition by G-CK. Functionally, G-CK reduced intracellular calcium overload, attenuated mitochondrial Ca 2+ accumulation and ROS generation, and ameliorated calcium overload-induced arrhythmia and myocardial oxidative injury in vivo . Conclusion: These findings identify G-CK as a major active metabolite of ginsenosides that alleviates calcium overload-associated cardiac injury by targeting CaMKII. This work provides mechanistic insight into the cardiovascular protective effects of ginseng metabolites and suggests that G-CK may serve as a potential lead compound for the development of novel calcium antagonists.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350, China",
    "Corresponding author."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sihan Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yixu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziyue Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenjuan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Min Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Gang Bai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6d6ms6kq3gr3z.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jgr.2026.101111",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S1226845326001375",
  "id": "6d6ms6kq3gr3z",
  "issns": [
    "1226-8453",
    "2093-4947"
  ],
  "landing_url": "https://doi.org/10.1016/j.jgr.2026.101111",
  "language": "en",
  "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",
      "Research Article"
    ],
    [
      "lcc",
      "QK1-989"
    ],
    [
      "openalex",
      "1312|Ginseng Biological Effects and Applications"
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  "pdf_url": "https://europepmc.org/articles/PMC13711400?pdf=render",
  "pmcid": "PMC13711400",
  "pmid": "42948178",
  "published": "2026-07-15",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/6d6ms6kq3gr3z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:31Z",
      "native_id": "3e51cb92e12c40bba76b2ab499582816",
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      "url": "https://doi.org/10.1016/j.jgr.2026.101111"
    },
    {
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      "url": "https://europepmc.org/article/MED/42948178"
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    {
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      "native_id": "PMC13711400",
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      "url": "https://doi.org/10.1016/j.jgr.2026.101111"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Ginseng Biological Effects and Applications",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Ginsenoside CK, a major active metabolite of ginsenosides, ameliorates calcium overload-induced arrhythmias and myocardial oxidative injury by targeting CaMKII",
  "title_text": "Ginsenoside CK, a major active metabolite of ginsenosides, ameliorates calcium overload-induced arrhythmias and myocardial oxidative injury by targeting CaMKII",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:11Z",
  "url": "https://research.draconitic.com/paper/6d6ms6kq3gr3z",
  "venue": "Journal of Ginseng Research",
  "versions": []
}