Department of Integrated Chinese and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
School of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China.
PLoS One. 2024 Jun 24;19(6):e0305903. doi: 10.1371/journal.pone.0305903. eCollection 2024.
Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification.
The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments.
A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1β, STAT3, MMP-9, and TGF-β1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-β1/Smad2/3.
QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-β1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.
肺纤维化（PF）是一种常见的间质性肺炎疾病，也发生在 COVID-19 幸存者中。用于治疗 COVID-19 幸存者 PF 的中药配方清肺化痰汤（QFHXD）抗 PF 作用的机制尚不清楚。本研究旨在通过网络药理学分析和实验验证，揭示 QFHXD 抗 PF 的相关机制。
从公共数据库中获得 QFHXD 的候选化学化合物及其用于治疗 PF 的潜在靶点，从而建立相应的 QFHXD“草药-化合物-靶点”网络。还构建了潜在靶点的蛋白质-蛋白质相互作用网络，以筛选核心靶点。此外，通过体内实验验证了基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析预测的靶点和通路。
从数据库中鉴定出 QFHXD 中的 188 种活性化合物和 50 个靶基因。KEGG 和 GO 分析鉴定出 QFHXD 的关键治疗靶点，如 PI3K/Akt、IL-6、TNF、IL-1β、STAT3、MMP-9 和 TGF-β1。QFHXD（呈剂量依赖性）和泼尼松在博莱霉素诱导的 PF 大鼠模型中通过 HE、Masson 染色和天狼猩红染色以及体内 Micro-CT 和免疫组织化学分析证实了抗 PF 作用。此外，QFHXD 显著抑制 PI3K/Akt/NF-κB 和 TGF-β1/Smad2/3 的活性。
QFHXD 通过抑制炎症和上皮间质转化显著减轻博莱霉素诱导的 PF。PI3K/Akt/NF-κB 和 TGF-β1/Smad2/3 通路可能是 QFHXD 治疗 PF 的潜在治疗作用机制。
