Ginsenoside Rk2 combined with dexamethasone enhances the anti neutrophilic asthma effect via STAT1/NLRP3-NETs-Th17/Treg axis
4 affiliations
- 1School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China
- 2College of Basic Medical Sciences, Jilin University, Changchun, 130021, China
- 3College of Basic Medical Sciences, Jilin University, Changchun, 130021, China; Corresponding author.
- 4School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China; Corresponding author.
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.
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BibTeX
@article{tan2026ginsenoside,
title = {{Ginsenoside Rk2 combined with dexamethasone enhances the anti neutrophilic asthma effect via STAT1/NLRP3-NETs-Th17/Treg axis}},
author = {Luying Tan and Junzhe Wu and Xiaoyu Geng and Jia Wang and Yuwei Liu and Liurong Zhang and Linxuan Liu and Fang Wang and Cuizhu Wang and Hongqiang Lin and Jinping Liu},
journal = {Journal of Ginseng Research},
year = {2026},
month = aug,
doi = {10.1016/j.jgr.2026.101116},
url = {https://doi.org/10.1016/j.jgr.2026.101116},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Ginsenoside Rk2 combined with dexamethasone enhances the anti neutrophilic asthma effect via STAT1/NLRP3-NETs-Th17/Treg axis
AU - Luying Tan
AU - Junzhe Wu
AU - Xiaoyu Geng
AU - Jia Wang
AU - Yuwei Liu
AU - Liurong Zhang
AU - Linxuan Liu
AU - Fang Wang
AU - Cuizhu Wang
AU - Hongqiang Lin
AU - Jinping Liu
PY - 2026
DA - 2026/08/04
JO - Journal of Ginseng Research
DO - 10.1016/j.jgr.2026.101116
UR - https://doi.org/10.1016/j.jgr.2026.101116
AB - 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.
SN - 1226-8453
SN - 2093-4947
ER -