Integration of transcriptomics and system pharmacology to reveal the therapeutic mechanism underlying Qingfei Xiaoyan Wan to treat allergic asthma

转录组学与系统药理学结合揭示清肺消炎丸治疗过敏性哮喘的治疗机制

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作者:Jing-Yi Hou, Jia-Rong Wu, Dong Xu, Yi-Bing Chen, Dan-Dan Shang, Shu Liu, Guan-Wei Fan, Yuan-Lu Cui

Conclusions

QFXYW may have mediated OVA-induced allergic asthma mainly through the hub genes CXCL2, CXCL1, and the cytokine signaling pathway. This finding will offer a novel strategy to explore effective and safe mechanism of Traditional Chinese Medicine (TCM) formula to treat allergic asthma.

Methods

BALB/c mice were sensitized with ovalbumin (OVA) to establish the allergic asthma model, and its success was confirmed with behavioral observations. Lung histopathological analysis, inflammatory pathology scores, transcription factors were used to evaluate the effects of QFXYW on allergic asthma. The therapeutic mechanism of QFXYW in treating allergic asthma through integrated transcriptomics and system pharmacology was then determined: hub genes were screened out by topological analysis and functional enrichment analysis were performed to identify key signaling pathway. Subsequently, quantitative RP-PCR and protein array were performed to detect the mRNA of hub genes and to predict the key pathway in OVA-induced allergic asthma, respectively.

Results

Our results demonstrated that QFXYW could significantly attenuate inflammatory cell infiltration, mucus secretion, and epithelial damage. The transcriptomics analysis found the six hub genes with the highest values- CXCL10, CXCL2, CXCL1, IL-6, CCL-5, and CCL-4 were screened out. Functional enrichment analysis showed that the differentially expressed genes (DEGs) were mainly enriched in the inflammatory response and cytokine signaling pathway. Moreover, the quantitative RT-PCR verification experiment found the CXCL2 and CXCL1 were significantly suppressed after treatment with QFXYW. The results of protein array showed that QFXYW inhibited the multi-cytokines of OVA-induced allergic asthma via cytokine signaling pathway. Conclusions: QFXYW may have mediated OVA-induced allergic asthma mainly through the hub genes CXCL2, CXCL1, and the cytokine signaling pathway. This finding will offer a novel strategy to explore effective and safe mechanism of Traditional Chinese Medicine (TCM) formula to treat allergic asthma.

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