Mechanisms of Shufeng Jiedu Capsule in treating bacterial pneumonia based on network pharmacology and experimental verification
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摘要:
目的：本研究旨在基于网络药理学和实验验证研究，探讨疏风解毒胶囊（SFJD）在体内治疗细菌性肺炎（BP）的内在机制。 方法：采用网络药理学方法筛选SFJD的活性化合物和潜在治疗靶点。建立多耐药性铜绿假单胞菌（MDR-PA）小鼠致死模型和MDR-PA肺炎模型，评价SFJD治疗细菌性肺炎的药效学作用。采用 Western blot 和 ELISA 检测 IL-17 信号通路和 JAK/STAT 信号通路的蛋白表达水平。 结果：经过筛选共得到172个SFJD的潜在成分，取交集后得到了200个SFJD治疗BP的潜在靶点，并在此基础上构建了SFJD成分-靶点-疾病相互作用网络。GO和KEGG富集显示，SFJD可调控IL-17信号通路和JAK/STAT信号通路。SFJD能明显降低死亡保护模型的死亡率，延长存活天数。SFJD能明显降低肺炎模型肺指数并改善肺部炎症浸润。SFJD可显著降低IL-17A、TRAF6、p-IκB/ IκB、NF-κB pp65、p-AKT/AKT、p-STAT3/ STAT3、p-STAT1/ STAT1的表达，以及IL-6、TNF-α 和IL-1β 的蛋白水平。 结论：结合网络药理学和体内研究发现，SFJD通过抑制IL-17通路和JAK/STAT信号通路发挥其对BP的治疗作用。本研究为SFJD治疗BP提供了新的证据。
Abstract:
Objective: The aim of this study was to investigate the underlying mechanism of Shufeng Jiedu Capsule (SFJD) for treating bacterial pneumonia (BP) in vivo based on network pharmacology and experimental verification study. Methods: Network pharmacology was used to screen the active compounds and target genes of SFJD. Then, the multi drug resistance-Pseudomonas aeruginosa (MDR-PA) mice lethal model and MDR-PA pneumonia model were established to evaluate the therapeutic effects and underlying mechanisms of SFJD. Western blot and ELISA were used to determinate the protein expression level of the IL-17 signaling pathway and JAK/STAT signaling pathway. Results: After screening, 172 potential components of SFJD were generated, based on which we constructed an SFJD-component-target-BP interaction network. The Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment revealed that SFJD could regulate the IL-17 signaling pathway and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Molecular docking showed that the potential target proteins had good combinations with the main active components. SFJD significantly reduced the mortality and prolonged survival days in lethal models. The lung index and pathological changes in the lung were also significantly decreased. SFJD could significantly decrease the expression of interleukin-17A (IL-17A), TNF receptor associated factor 6 (TRAF6), phospho-inhibitor of nuclear factor-kappa B (p-IjB)/inhibitor of NF-jB (IjB), phospho-NF-jB p65 (p-NF-jB p65), phospho-protein kinase B (p-AKT)/AKT, phospho-signal transducer and activator of transcription 3 (p -STAT3)/STAT3, phospho-signal transducer and activator of transcription 1 (p-STAT1)/STAT1, and the protein level of interleukin-6 (IL-6), tumor necrosis factor a (TNF-a), and IL-1b. Conclusion: Combined with network pharmacology and in vivo study, it was found that SFJD exerted its therapeutic effects on BP by inhibiting the IL-17 pathway and JAK/STAT signaling pathway. This study provides new evidence for SFJD in treatment of BP.
关键词:
细菌性肺炎;IL-17 信号通路;JAK/STAT 信号通路;分子对接;网络药理学;疏风解毒胶囊
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This work was supported by the National Natural Science Foundation of China (No. 82104500), the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (No. CI2021B015), National Natural Science Foundation of China (No. 82141206), Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (No. CI2021A04620). We thank Shanghai NewCore Biotechnology Co., Ltd. (https:// www.bioinformatics.com.cn) for providing data analysis and visualization support.
Yingli Xu, Lei Bao, Ronghua Zhao, Zihan Geng, Shuran Li, Bo Pang, Qiyue Sun, Shanshan Guo, Xiaolan Cui *, Jing Sun *. Mechanisms of Shufeng Jiedu Capsule in treating bacterial pneumonia based on network pharmacology and experimental verification[J]. Chinese Herbal Medicines (CHM),2024,16(4):656-666
