{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:30:40Z","timestamp":1791430240455,"version":"4.3.3"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274274"],"award-info":[{"award-number":["82274274"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3502600"],"award-info":[{"award-number":["2023YFC3502600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytochemical Analysis"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Traditional Chinese medicine (TCM) comprises complex matrices with largely unidentified constituents, which has resulted in clinical insecurity and difficulty in quality control. Substantial efforts have been made to screen drug combinations to replace TCM formulas; however, these methods fail to consider biotransformation among phytochemicals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>A \u201cbiomimetic extracted substances (BESs)\u201d based strategy was proposed\u2014which fully considers in\u00a0vivo processes\u2014to identify anti\u2013chronic obstructive pulmonary disease (COPD) combinations from Bufei Yishen formula (BYF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BES of each BYF ingredient was prepared via sequential coculture with artificial gastric juice, intestinal fluid, intestinal flora, and liver S9, with the compositions identified by UHPLC\u2010Q Exactive MS. Cytotoxicity and effects on IL\u20106 secretion were analyzed in LPS\u2010induced macrophages to compare BYF ingredients and their BESs, screening for optimal anti\u2010COPD combinations. Therapeutic effects were evaluated in a smoking\u2010induced rat COPD model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty\u2010six metabolites were identified in the BESs of five BYF ingredients from different metabolic sites. Bionic extraction reduced cytotoxicity and changed the anti\u2010inflammatory efficacy of BYF ingredients. Based on BES activity, nobiletin and icariin showed the highest anti\u2010inflammatory activity. In the COPD model, their combination significantly alleviated lung injury and inflammatory responses. Combined with metabolic analysis, the efficacy of nobiletin may be attributed to its prototype component, whereas icariin may be attributed to its deglycosylated metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BESs more closely mimics the cytotoxicity and bioactivity of TCM after metabolism. Screening based on BES thus improves consistency between in\u00a0vitro and in\u00a0vivo results. Using this strategy, nobiletin and icariin were identified as a potentially effective combination within BYF for alleviating COPD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pca.70070","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T01:31:10Z","timestamp":1775439070000},"page":"636-653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Strategy of Screening Drug Combination From Traditional Chinese Medicine Based on Biomimetic Extracted Substances: Bufei Yishen Formula as a Case"],"prefix":"10.1002","volume":"37","author":[{"given":"Xuemei","family":"Xu","sequence":"first","affiliation":[{"name":"Co\u2010Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan &amp; Education Ministry of P.R. China Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Henan Key Laboratory of Chinese Medicine for Respiratory Disease Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Academy of Chinese Medical Sciences Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Qin","sequence":"additional","affiliation":[{"name":"Co\u2010Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan &amp; Education Ministry of P.R. China Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Henan Key Laboratory of Chinese Medicine for Respiratory Disease Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Academy of Chinese Medical Sciences Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxia","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Pharmacy Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuyue","family":"Yin","sequence":"additional","affiliation":[{"name":"Co\u2010Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan &amp; Education Ministry of P.R. China Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Henan Key Laboratory of Chinese Medicine for Respiratory Disease Henan University of Chinese Medicine  Zhengzhou China"},{"name":"College of Pharmacy Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Li","sequence":"additional","affiliation":[{"name":"Co\u2010Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan &amp; Education Ministry of P.R. 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China Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Henan Key Laboratory of Chinese Medicine for Respiratory Disease Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Academy of Chinese Medical Sciences Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Co\u2010Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan &amp; Education Ministry of P.R. China Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Henan Key Laboratory of Chinese Medicine for Respiratory Disease Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Academy of Chinese Medical Sciences Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6485-2371","authenticated-orcid":false,"given":"Jiansheng","family":"Li","sequence":"additional","affiliation":[{"name":"Co\u2010Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan &amp; Education Ministry of P.R. China Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Henan Key Laboratory of Chinese Medicine for Respiratory Disease Henan University of Chinese Medicine  Zhengzhou China"},{"name":"Lung Disease Diagnosis and Treatment Center, National Medical Center The First Affiliated Hospital of Henan University of Chinese Medicine  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6172-1328","authenticated-orcid":false,"given":"Xinguang","family":"Liu","sequence":"additional","affiliation":[{"name":"Co\u2010Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan &amp; Education Ministry of P.R. 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