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Potential Components and Mechanisms of Ganlu Xiaodu Dan in Treatment of Viral Pneumonia

  • role： First author第一作者
  • Affiliation：

    Graduate School，Hebei University of Chinese Medicine，Shijiazhuang 050091，China

  • Email：ydyy1995@163.com
  • Introduction：张玮超，在读博士，从事急危重症研究及中医疫病研究，E-mail：ydyy1995@163.com
ZHANG Weichao1,  
  • Affiliation：

    Graduate School，Hebei University of Chinese Medicine，Shijiazhuang 050091，China

LI Yayun1,  
  • Affiliation：

    Graduate School，Hebei University of Chinese Medicine，Shijiazhuang 050091，China

GAO Tianci1,  
  • Affiliation：

    Graduate School，Hebei University of Chinese Medicine，Shijiazhuang 050091，China

HOU Mengxing1,  
  • Affiliation：

    The First Affiliated Hospital，Hebei University of Chinese Medicine，Shijiazhuang 050011，China

XU Wenzhong2,  
  • role： Corresponding author通信作者
  • Affiliation：

    The First Affiliated Hospital，Hebei University of Chinese Medicine，Shijiazhuang 050011，China

  • Email：chenfenqiao@126.com
  • Introduction：陈分乔，博士，教授，主任医师从事急危重症及中医疫病研究，E-mail：chenfenqiao@126.com
CHEN Fenqiao2*

résumé

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation.MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation.ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）.ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

mots-clés

network pharmacology;molecular docking;Ganlu Xiaodu Dan;viral pneumonia;phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway

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