PMID- 35074456 OWN - NLM STAT- MEDLINE DCOM- 20220316 LR - 20220316 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 289 DP - 2022 May 10 TI - Network pharmacology analysis uncovers the effect on apoptotic pathway by Bu-Fei formula for COPD treatment. PG - 115022 LID - S0378-8741(22)00056-3 [pii] LID - 10.1016/j.jep.2022.115022 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: The Bu-Fei formula (BFF) has a positive effect on chronic obstructive pulmonary disease (COPD). However, its therapeutic mechanisms against COPD remain unknown. AIM OF THE STUDY: To explore BFF's therapeutic effect on COPD and pharmacological mechanisms. MATERIALS AND METHODS: First, the effect of BFF on rats with COPD was studied. Rats were randomly assigned to the blank, COPD, BFF treatment, and aminophylline (APL) treatment groups. From weeks 1-8, the COPD model was established by Klebsiella pneumoniae (KP) and cigarette smoke. Then, rats were given corresponding treatment for 8 weeks. The lung function of the rats was analyzed by whole-body plethysmography and pulmonary function testing, lung histopathology by electron microscopy and hematoxylin and eosin staining, and protein levels by immunohistochemistry. Next, the key components and targets of BFF in COPD were screened by network pharmacology analysis. Finally, the possible mechanism was verified through molecular docking and in vivo experiments. RESULTS: BFF significantly improved lung function and lung histopathology in COPD rats and inhibit inflammation and collagen deposition in lung tissues. Also, 46 bioactive compounds and 136 BFF targets related to COPD were identified; among them, 3 compounds (quercetin, luteolin, and nobiletin) and 6 core targets (Akt1, BCL2, NF-kappaB p65, VEGFA, MMP9, and Caspase 8) were the key molecules associated with the mechanisms of BFF. The target enrichment analysis suggested that BFF's mechanisms might involve the apoptosis-related pathway; this possibility was supported by the molecular docking data. Lastly, BFF was indicated to increase the expression of core target genes and the production of apoptosis-related proteins. CONCLUSIONS: BFF affects COPD by regulating the apoptosis-related pathways and targets. CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Zhang, Lan-Xi AU - Zhang LX AD - Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed By Henan Province & Education Ministry of PR China, Zhengzhou, 450046, Henan Province, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China. Electronic address: 13140101013@163.com. FAU - Tian, Yan-Ge AU - Tian YG AD - Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed By Henan Province & Education Ministry of PR China, Zhengzhou, 450046, Henan Province, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China; Academy of Chinese Medicine Science, Henan University of Chinese Medicine, Zhengzhou, Henan, China. Electronic address: yange0910@126.com. FAU - Zhao, Peng AU - Zhao P AD - Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed By Henan Province & Education Ministry of PR China, Zhengzhou, 450046, Henan Province, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China; Academy of Chinese Medicine Science, Henan University of Chinese Medicine, Zhengzhou, Henan, China. Electronic address: zhaopeng871@126.com. FAU - Feng, Su-Xiang AU - Feng SX AD - Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed By Henan Province & Education Ministry of PR China, Zhengzhou, 450046, Henan Province, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China. Electronic address: fengsx221@163.com. FAU - Han, Xiao-Xiao AU - Han XX AD - Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed By Henan Province & Education Ministry of PR China, Zhengzhou, 450046, Henan Province, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China. Electronic address: 2510592076@qq.com. FAU - Li, Jian-Sheng AU - Li JS AD - Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed By Henan Province & Education Ministry of PR China, Zhengzhou, 450046, Henan Province, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, China. Electronic address: li_js8@163.com. LA - eng PT - Journal Article DEP - 20220122 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Drugs, Chinese Herbal) RN - 0 (bu-fei decoction) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Collagen/metabolism MH - Disease Models, Animal MH - Drugs, Chinese Herbal/*pharmacology MH - Inflammation/drug therapy/pathology MH - Network Pharmacology MH - Pulmonary Disease, Chronic Obstructive/*drug therapy MH - Rats MH - Rats, Sprague-Dawley MH - Respiratory Function Tests OTO - NOTNLM OT - Apoptosis pathway OT - Bu-Fei formula OT - Chronic obstructive pulmonary disease OT - Compounds OT - Core targets OT - Network pharmacology EDAT- 2022/01/26 06:00 MHDA- 2022/03/17 06:00 CRDT- 2022/01/25 05:40 PHST- 2021/09/07 00:00 [received] PHST- 2022/01/16 00:00 [revised] PHST- 2022/01/18 00:00 [accepted] PHST- 2022/01/26 06:00 [pubmed] PHST- 2022/03/17 06:00 [medline] PHST- 2022/01/25 05:40 [entrez] AID - S0378-8741(22)00056-3 [pii] AID - 10.1016/j.jep.2022.115022 [doi] PST - ppublish SO - J Ethnopharmacol. 2022 May 10;289:115022. doi: 10.1016/j.jep.2022.115022. Epub 2022 Jan 22.