{
  "abstract": "Background: Neutrophilic asthma (NA) is a severe, corticosteroid-resistant phenotype associated with neutrophil extracellular traps (NETs) formation and Th17/Treg imbalance. Cold exposure exacerbates NA progression, increasing the global clinical burden. Currently, combination therapy with corticosteroids is considered a viable approach. This study aimed to investigate the therapeutic potential and mechanisms of ginsenoside Rk2 (Rk2) combined with dexamethasone (DEX) against cold-stimulated neutrophilic asthma (CSNA). Methods: A corticosteroid-resistant BEAS-2B cell model was established by NTHi stimulation. A CSNA mouse model was established via ovalbumin sensitization, NTHi infection, and cold stimulation, followed by Rk2 and/or DEX treatment. Airway hyperresponsiveness, histopathology, and neutrophil infiltration were measured to assess therapeutic efficacy. Th17/Treg populations were analyzed by flow cytometry. NETs formation was quantified in PMA-stimulated primary mouse neutrophils. A NETs-naïve CD4 + T cell co-culture system was used to examine the causal role of NETs in Th17/Treg imbalance. Transcriptomics and agonist-based gain-of-function experiments were conducted to validate the mechanism of Rk2 combined with DEX. Results: Rk2 reversed DEX resistance by rebalancing GR α /GR β , upregulating HDAC2, and promoting GR α nuclear translocation. Compared with monotherapy, Rk2 combined with DEX ameliorated airway inflammation and restored Th17/Treg homeostasis. Mechanistically, this combination therapy suppressed NETs formation by reducing NETs components, DNA release and ROS generation. NETs drove Th17/Treg imbalance via STAT1/NLRP3 inflammasome axis. Pharmacological activation of either STAT1 or NLRP3 reversed the beneficial effects. Conclusion: Our findings demonstrate for the first time that Rk2, a potent natural corticosteroid potentiator, acts in combination with DEX to alleviate CSNA by suppressing the STAT1/NLRP3 inflammasome-NETs-Th17/Treg cascade.",
  "abstract_shown": true,
  "affiliations": [
    "School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China",
    "College of Basic Medical Sciences, Jilin University, Changchun, 130021, China",
    "College of Basic Medical Sciences, Jilin University, Changchun, 130021, China; Corresponding author.",
    "School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China; Corresponding author."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Luying Tan"
    },
    {
      "affs": [
        0
      ],
      "name": "Junzhe Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyu Geng"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuwei Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Liurong Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Linxuan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Fang Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Cuizhu Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Hongqiang Lin"
    },
    {
      "affs": [
        3
      ],
      "name": "Jinping Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/05r58zkm3qgfg.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jgr.2026.101116",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S1226845326001429",
  "id": "05r58zkm3qgfg",
  "issns": [
    "1226-8453",
    "2093-4947"
  ],
  "landing_url": "https://doi.org/10.1016/j.jgr.2026.101116",
  "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",
      "2737|Asthma and respiratory diseases"
    ]
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  "openalex": "W7172418023",
  "pdf_url": "https://europepmc.org/articles/PMC13711451?pdf=render",
  "pmcid": "PMC13711451",
  "pmid": "42948214",
  "published": "2026-08-04",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/05r58zkm3qgfg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:35Z",
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      "url": "https://doi.org/10.1016/j.jgr.2026.101116"
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      "url": "https://europepmc.org/article/MED/42948214"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Asthma and respiratory diseases",
      "subfield": "physiology"
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  ],
  "title": "Ginsenoside Rk2 combined with dexamethasone enhances the anti neutrophilic asthma effect via STAT1/NLRP3-NETs-Th17/Treg axis",
  "title_text": "Ginsenoside Rk2 combined with dexamethasone enhances the anti neutrophilic asthma effect via STAT1/NLRP3-NETs-Th17/Treg axis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:13Z",
  "url": "https://research.draconitic.com/paper/05r58zkm3qgfg",
  "venue": "Journal of Ginseng Research",
  "versions": []
}