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In addition, we established a rat model of cigarette smoke- and bacterial infection-induced COPD to validate the mechanisms of BYF action that were predicted in systems pharmacology study. The systems pharmacology model derived 216 active compounds from BYF and 195 potential targets related to various diseases. The compound-target network showed that each herbal drug in the BYF formula acted on similar targets, suggesting potential synergistic effects among these herbal drugs. The ClueGo assay, a Cytoscape plugin, revealed that most targets were related to activation of MAP kinase and matrix metalloproteinases. By using target-diseases network analysis, we found that BYF had great potential to treatment of multiple diseases, such as respiratory tract diseases, immune system and cardiovascular diseases. Furthermore, we found that BYF had the ability to prevent COPD and its comorbidities, such as ventricular hypertrophy, <jats:italic>in vivo<\/jats:italic>. Moreover, BYF inhibited the inflammatory cytokine and hypertrophic factors expression, protease-antiprotease imbalance and the collagen deposition, which may be the underlying mechanisms of action of BYF.<\/jats:p>","DOI":"10.1038\/srep15290","type":"journal-article","created":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T13:03:15Z","timestamp":1444914195000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease"],"prefix":"10.1038","volume":"5","author":[{"given":"Jiansheng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yange","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"key":"BFsrep15290_CR1","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1164\/rccm.201209-1665OC","volume":"187","author":"LE Vanfleteren","year":"2013","unstructured":"Vanfleteren, L. 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