Chinese Journal of Pharmacovigilance ›› 2026, Vol. 23 ›› Issue (10): 1115-1122.
DOI: 10.19803/j.1672-8629.20260697

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Isoorientin from Gentiana dahurica Fisch. Flower regulates COPD-related airway inflammation via MAPK pathway: an in vitro study of mechanisms

Song Wenxuan1,2, Zhou Shuhong2, Zhang Wenxue1,2, Wang Ning2, Guo Qi2,3, Ma Ao2,3, Wang Minjie2,4#, Yi Letai2,5*   

  1. 1School of Pharmacy, Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China;
    2Key Laboratory of Quality Research and Efficacy Evaluation of Traditional Chinese Medicine (Mongolian medicine), Inner Mongolia Medical University, Hohhot Inner Mongolia 010059, China;
    3School of Pharmacy, Baotou Medical College, Baotou Inner Mongolia 014040, China;
    4School of Basic Medicine, Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China;
    5Medical Innovation Center for Nationalities, Inner Mongolia Medical University, Hohhot Inner Mongolia 010110, China
  • Received:2026-08-24 Online:2026-10-15 Published:2026-10-16

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Abstract: Objective To explore the role of ISO, an active component of Gentiana dahurica Fisch. Flower in attenuating airway inflammation related to chronic obstructive pulmonary disease (COPD) and the molecular mechanism. Methods ISO, gentiopicroside and loganic acid in Gentiana dahurica Fisch. Flower were quantified via LC-MS/MS. Lipopolysa-ccharide (LPS, 5 μg·mL-1) was used to establish an in-vitro COPD-related inflammatory model in BEAS-2B human bronchial epithelial cells. CCK-8 assay was performed to screen the safe ISO dosage and evaluate its effect of cytoprotection. RT-qPCR was adopted to detect mRNA levels of inflammatory mediators. Transcriptome sequencing was employed to screen differentially expressed genes and key enriched pathways. RT-qPCR and Western blot were used to measure the expression levels of core MAPK-related genes and proteins. Molecular docking was conducted to predict the binding affinity between isoorientin and target proteins. Results ISO was the leading active component of Gentiana dahurica Fisch. Flower. The safe intervention condition of ISO was 5 μmol•L⁻¹ and 12 hours of intervention. Compared with the control group, LPS markedly reduced cell viability (P<0.001) while 5 μmol·L-1 ISO restored cell viability in the model group (P<0.01). The mRNA levels of IL-6, IL-1β, IL-8, TNF-α, MMP-9 and CXCL5 were significantly elevated in LPS-treated cells (P<0.001), and ISO markedly suppressed these up-regulated transcripts (P<0.01, P<0.001). Transcriptome enrichment identified the MAPK pathway as a major anti-inflammatory target. LPS up-regulated EREG, MAPK8 (JNK1) and FOS at the mRNA level (P<0.01, P<0.001), increased EREG, c-Fos protein abundance and elevated the p-JNK/JNK ratio (P<0.01), but ISO reversed these alterations and restrained excessive MAPK activation (P<0.01, P<0.001). Molecular docking suggested that binding energies between ISO and EREG, JNK1 and c-Fos were all less than -5 kcal·mol-1, suggesting favorable binding potentials. Conclusion ISO derived from Gentiana dahurica Fisch. Flower may inhibit aberrant MAPK signaling, reduce pro-inflammatory mediator release and alleviate LPS-provoked airway inflammatory injury related to COPD by interacting with key MAPK-related proteins.

Key words: Gentiana dahurica Fisch. Flower, Isoorientin, Chronic Obstructive Pulmonary Disease (COPD), COPD Related Airway Inflammation, In vitro Cell Experiment, BEAS-2B Human Bronchial Epithelial Cells, Transcriptomics

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