{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:02:28Z","timestamp":1771048948727,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204599"],"award-info":[{"award-number":["82204599"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173957"],"award-info":[{"award-number":["82173957"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Qishen granule (QSG) is a widely prescribed herbal formula for the treatment of chronic heart failure. The mechanisms of action of QSG have been clarified; however, the effective substances remain unclear. This lack of clarity hinders quality control and the consistency of the clinical efficacy of QSG. Methods: In the present study, an integrated strategy for an efficacy- and in vivo exposure-oriented study involving metabolite profiling, molecular docking, in vitro bioassays, and in vivo pharmacokinetics was proposed for investigating the potentially effective components of QSG. Results: In total, 101 prototypes\/metabolites were preliminarily identified and characterized by UHPLC-Q TOF-MS\/MS. Molecular docking of the absorbed constituents with targeted proteins suggested that 49 potential components were highly related to chronic heart failure (CHF). Then, the effectiveness of these potential compounds was verified by the oxygen glucose deprivation\/re-oxygenation (OGD\/R)-induced H9c2 cell model. As a result, 14 active components were screened, and their median effective concentration (EC50) was calculated and utilized to generate the weight coefficient for the bioeffect of each constituent. By exploring the kinetic parameters of the active compounds in a pharmacokinetic study, the exposure levels of these pharmacologically active compounds were determined by area under the curve (AUC0\u2192\u221e) calculations. Finally, by calculating the effect\u2013constituent index (ECI) for each compound, five key active components (cryptochlorogenic acid, chlorogenic acid, isochlorogenic acid C, salvianolic acid B, and neochlorogenic acid), which possess both pharmacological activities and higher exposure levels, were revealed to be the key effective substances of QSG. Conclusions: This study is the first to combine pharmacological activities with in vivo exposure for investigating the effective components of QSG. The identification of key active components provides a foundation for improving the quality control of QSG in clinics. The efficacy- and in vivo exposure-oriented integrated method could provide reliable references for other traditional Chinese medicines (TCMs).<\/jats:p>","DOI":"10.3390\/ph18101584","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:27:29Z","timestamp":1760963249000},"page":"1584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Efficacy- and In Vivo Exposure-Oriented Integrated Study to Investigate the Effective Components of Qishen Granule"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5262-3750","authenticated-orcid":false,"given":"Yueting","family":"Li","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tengteng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Huo","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiale","family":"Gao","sequence":"additional","affiliation":[{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1186\/s13063-017-2193-z","article-title":"Safety and efficacy of Qishen granules in patients with chronic heart failure: Study protocol for a randomized controlled trial","volume":"18","author":"Wang","year":"2017","journal-title":"Trials"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.phrs.2016.10.026","article-title":"Systems-biology dissection of mechanisms and chemical basis of herbal formula in treating chronic myocardial ischemia","volume":"114","author":"Guo","year":"2016","journal-title":"Pharmacol. 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