Mechanisms of Shufeng Jiedu Capsule in treating bacterial pneumonia based on network pharmacology and experimental verification

doi:https://doi.org/10.1016/j.chmed.2024.01.002

Archive > Volume 16 Issue 4 > 2024,16(4):656-666. DOI:https://doi.org/10.1016/j.chmed.2024.01.002 Prev Next

基于網(wǎng)絡(luò)藥理學(xué)和實(shí)驗(yàn)驗(yàn)證探討疏風(fēng)解毒膠囊治療細(xì)菌性肺炎的藥效及機(jī)制研究

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Mechanisms of Shufeng Jiedu Capsule in treating bacterial pneumonia based on network pharmacology and experimental verification

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摘要:

目的：本研究旨在基于網(wǎng)絡(luò)藥理學(xué)和實(shí)驗(yàn)驗(yàn)證研究，探討疏風(fēng)解毒膠囊（SFJD）在體內(nèi)治療細(xì)菌性肺炎（BP）的內(nèi)在機(jī)制。方法：采用網(wǎng)絡(luò)藥理學(xué)方法篩選SFJD的活性化合物和潛在治療靶點(diǎn)。建立多耐藥性銅綠假單胞菌（MDR-PA）小鼠致死模型和MDR-PA肺炎模型，評(píng)價(jià)SFJD治療細(xì)菌性肺炎的藥效學(xué)作用。采用 Western blot 和 ELISA 檢測(cè) IL-17 信號(hào)通路和 JAK/STAT 信號(hào)通路的蛋白表達(dá)水平。結(jié)果：經(jīng)過(guò)篩選共得到172個(gè)SFJD的潛在成分，取交集后得到了200個(gè)SFJD治療BP的潛在靶點(diǎn)，并在此基礎(chǔ)上構(gòu)建了SFJD成分-靶點(diǎn)-疾病相互作用網(wǎng)絡(luò)。GO和KEGG富集顯示，SFJD可調(diào)控IL-17信號(hào)通路和JAK/STAT信號(hào)通路。SFJD能明顯降低死亡保護(hù)模型的死亡率，延長(zhǎng)存活天數(shù)。SFJD能明顯降低肺炎模型肺指數(shù)并改善肺部炎癥浸潤(rùn)。SFJD可顯著降低IL-17A、TRAF6、p-IκB/ IκB、NF-κB pp65、p-AKT/AKT、p-STAT3/ STAT3、p-STAT1/ STAT1的表達(dá)，以及IL-6、TNF-α 和IL-1β 的蛋白水平。結(jié)論：結(jié)合網(wǎng)絡(luò)藥理學(xué)和體內(nèi)研究發(fā)現(xiàn)，SFJD通過(guò)抑制IL-17通路和JAK/STAT信號(hào)通路發(fā)揮其對(duì)BP的治療作用。本研究為SFJD治療BP提供了新的證據(jù)。

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.

關(guān)鍵詞:

細(xì)菌性肺炎;IL-17 信號(hào)通路;JAK/STAT 信號(hào)通路;分子對(duì)接;網(wǎng)絡(luò)藥理學(xué);疏風(fēng)解毒膠囊

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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.

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