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Background <p>Qingre Runzao oral liquid (QRRZ) is a Chinese medicine prescription. Previous studies have confirmed its good therapeutic effect on bronchial asthma (BA), but the mechanisms remain unclear. This study aims to clarify the anti-BA effect and mechanisms of QRRZ, and further reveal the key compounds of QRRZ that ameliorate BA.</p> Methods <p>Firstly, the BA model mice were used to evaluate the therapeutic effect of QRRZ on BA. Then, RNA-seq analysis was performed to reveal the key targets and mechanisms of QRRZ in ameliorating BA, and the results were verified by RT-PCR and Western Blotting. Molecular docking, molecular dynamics simulation, and CETSA were used to screen the key compounds of QRRZ in ameliorating BA. The potential of key compounds on BA was evaluated in vitro. Finally, the mechanisms were verified, and a rescue experiment was conducted.</p> Results <p>QRRZ can ameliorate bronchial pathological changes and airway hyperresponsiveness, alleviate the progression of BA by reducing inflammatory cell infiltration, especially neutrophils. QRRZ significantly inhibits the expression of MUC5AC and Th2-related cytokines IL-6 and IL-13 in BALF solution and upregulates the Th1-related cytokine IL-2. RNA-seq results showed QRRZ mainly blocks CXCL9/CXCR3 axis and inhibits RAS/ERK pathway activation to ameliorate BA, and CXCL9 is the key protein of QRRZ. Molecular docking and molecular dynamics simulation results showed that Ophiopogonin D (Oph D) can bind to CXCR3 (CXCL9 receptor) tightly. CETSA and CO-IP assays confirm that Oph D can bind stably to CXCR3. Then, Oph D exhibited potent anti-BA efficacy both in <i>vitro</i> and in <i>vivo</i>. Furthermore, results indicated Oph D can down-regulate CXCL9 and block the CXCL9/CXCR3 axis to inhibit RAS/ERK pathway activation in 16HBE cells.</p> Conclusion <p>QRRZ could block the CXCL9/CXCR3 axis to inhibit RAS/ERK pathway activation, reduce neutrophil infiltration in bronchioles, and improve bronchial asthma. Among these, Oph D is the key component of QRRZ in ameliorating BA.</p>

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Qingre Runzao oral liquid and its key compound ophiopogonin D inhibit CXCL9 and block CXCL9/CXCR3 axis to ameliorate asthma by suppressing RAS/ERK pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Lingxue Jiang,
  • Huan Li,
  • Wenping Bao,
  • Aihua Zhang,
  • Shiyu Guo,
  • Jianguo Sun,
  • Dongyun Li,
  • Danxia Wei

摘要

Background

Qingre Runzao oral liquid (QRRZ) is a Chinese medicine prescription. Previous studies have confirmed its good therapeutic effect on bronchial asthma (BA), but the mechanisms remain unclear. This study aims to clarify the anti-BA effect and mechanisms of QRRZ, and further reveal the key compounds of QRRZ that ameliorate BA.

Methods

Firstly, the BA model mice were used to evaluate the therapeutic effect of QRRZ on BA. Then, RNA-seq analysis was performed to reveal the key targets and mechanisms of QRRZ in ameliorating BA, and the results were verified by RT-PCR and Western Blotting. Molecular docking, molecular dynamics simulation, and CETSA were used to screen the key compounds of QRRZ in ameliorating BA. The potential of key compounds on BA was evaluated in vitro. Finally, the mechanisms were verified, and a rescue experiment was conducted.

Results

QRRZ can ameliorate bronchial pathological changes and airway hyperresponsiveness, alleviate the progression of BA by reducing inflammatory cell infiltration, especially neutrophils. QRRZ significantly inhibits the expression of MUC5AC and Th2-related cytokines IL-6 and IL-13 in BALF solution and upregulates the Th1-related cytokine IL-2. RNA-seq results showed QRRZ mainly blocks CXCL9/CXCR3 axis and inhibits RAS/ERK pathway activation to ameliorate BA, and CXCL9 is the key protein of QRRZ. Molecular docking and molecular dynamics simulation results showed that Ophiopogonin D (Oph D) can bind to CXCR3 (CXCL9 receptor) tightly. CETSA and CO-IP assays confirm that Oph D can bind stably to CXCR3. Then, Oph D exhibited potent anti-BA efficacy both in vitro and in vivo. Furthermore, results indicated Oph D can down-regulate CXCL9 and block the CXCL9/CXCR3 axis to inhibit RAS/ERK pathway activation in 16HBE cells.

Conclusion

QRRZ could block the CXCL9/CXCR3 axis to inhibit RAS/ERK pathway activation, reduce neutrophil infiltration in bronchioles, and improve bronchial asthma. Among these, Oph D is the key component of QRRZ in ameliorating BA.