RESUMO
ObjectiveTo investigate the targets and mechanism of Baofeikang granules in the treatment of pulmonary fibrosis based on network pharmacology and verify the predicted mechanism based on animal experiment. MethodThe active ingredients and targets of Baofeikang granules were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform， and the targets of pulmonary fibrosis were searched in various disease databases. The common targets shared by Baofeikang granules and the disease were extracted for the establishment of the protein-protein interaction （PPI） network in STRING. Cytoscape 3.8.0 was used to analyze the network topology of the key targets and to establish the ''active ingredient-target'' network. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed on the core targets to explore their possible molecular mechanisms. The rats were assigned into four groups： normal group， model group， prednisone acetate group， and Baofeikang granules group. The rat model of interstitial lung fibrosis was established by tracheal instillation of bleomycin. After 21 days of gavage， the lung tissues of rats were stained with hemotoxylin and eosin （HE） for the observation of morphological changes， and phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt） were detected via immunohistochemical （IHC） staining. ResultBased on network pharmacology， 18 key targets of Baofeikang granules were identified for the treatment of pulmonary interstitial fibrosis， including Akt1， mitogen-activated protein kinase （MAPK） 1， myelocytomatosis oncogene （MYC）， hypoxia-inducible factor-1α （HIF-1α）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， and Runt-related transcription factor （RUNX2）. KEGG pathway enrichment predicted that Baofeikang granules exerted anti-fibrotic effect mainly through PI3K/Akt， tumor necrosis factor （TNF）， and interleukin-17 （IL-17） signaling pathways. The IHC results in animal experiment showed that the protein levels of PI3K and Akt were lower in the Baofeikang granules group than in the model group （P<0.05， P<0.01）. ConclusionBaofeikang granules has low toxicity， multiple targets， and multiple pathways in the treatment of pulmonary fibrosis. It may alleviate pulmonary fibrosis through regulating PI3K/Akt signaling pathway， so as to improve the lung function.
RESUMO
ObjectiveTo investigate the targets and mechanism of Baofeikang granules in the treatment of pulmonary fibrosis based on network pharmacology and verify the predicted mechanism based on animal experiment. MethodThe active ingredients and targets of Baofeikang granules were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform， and the targets of pulmonary fibrosis were searched in various disease databases. The common targets shared by Baofeikang granules and the disease were extracted for the establishment of the protein-protein interaction （PPI） network in STRING. Cytoscape 3.8.0 was used to analyze the network topology of the key targets and to establish the ''active ingredient-target'' network. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed on the core targets to explore their possible molecular mechanisms. The rats were assigned into four groups： normal group， model group， prednisone acetate group， and Baofeikang granules group. The rat model of interstitial lung fibrosis was established by tracheal instillation of bleomycin. After 21 days of gavage， the lung tissues of rats were stained with hemotoxylin and eosin （HE） for the observation of morphological changes， and phosphatidylinositol 3-kinase （PI3K） and protein kinase B （Akt） were detected via immunohistochemical （IHC） staining. ResultBased on network pharmacology， 18 key targets of Baofeikang granules were identified for the treatment of pulmonary interstitial fibrosis， including Akt1， mitogen-activated protein kinase （MAPK） 1， myelocytomatosis oncogene （MYC）， hypoxia-inducible factor-1α （HIF-1α）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， and Runt-related transcription factor （RUNX2）. KEGG pathway enrichment predicted that Baofeikang granules exerted anti-fibrotic effect mainly through PI3K/Akt， tumor necrosis factor （TNF）， and interleukin-17 （IL-17） signaling pathways. The IHC results in animal experiment showed that the protein levels of PI3K and Akt were lower in the Baofeikang granules group than in the model group （P<0.05， P<0.01）. ConclusionBaofeikang granules has low toxicity， multiple targets， and multiple pathways in the treatment of pulmonary fibrosis. It may alleviate pulmonary fibrosis through regulating PI3K/Akt signaling pathway， so as to improve the lung function.