{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:40:07Z","timestamp":1785444007181,"version":"3.56.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018570","name":"Special Project of Central Government for Local Science and Technology Development of Hubei Province","doi-asserted-by":"publisher","award":["206Z2501G"],"award-info":[{"award-number":["206Z2501G"]}],"id":[{"id":"10.13039\/501100018570","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018570","name":"Special Project of Central Government for Local Science and Technology Development of Hubei Province","doi-asserted-by":"publisher","award":["20372502D"],"award-info":[{"award-number":["20372502D"]}],"id":[{"id":"10.13039\/501100018570","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018570","name":"Special Project of Central Government for Local Science and Technology Development of Hubei Province","doi-asserted-by":"publisher","award":["H2019423050"],"award-info":[{"award-number":["H2019423050"]}],"id":[{"id":"10.13039\/501100018570","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018570","name":"Special Project of Central Government for Local Science and Technology Development of Hubei Province","doi-asserted-by":"publisher","award":["2021100"],"award-info":[{"award-number":["2021100"]}],"id":[{"id":"10.13039\/501100018570","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hebei Provincial Key Research and Development","award":["206Z2501G"],"award-info":[{"award-number":["206Z2501G"]}]},{"name":"Hebei Provincial Key Research and Development","award":["20372502D"],"award-info":[{"award-number":["20372502D"]}]},{"name":"Hebei Provincial Key Research and Development","award":["H2019423050"],"award-info":[{"award-number":["H2019423050"]}]},{"name":"Hebei Provincial Key Research and Development","award":["2021100"],"award-info":[{"award-number":["2021100"]}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["206Z2501G"],"award-info":[{"award-number":["206Z2501G"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["20372502D"],"award-info":[{"award-number":["20372502D"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["H2019423050"],"award-info":[{"award-number":["H2019423050"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["2021100"],"award-info":[{"award-number":["2021100"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Project of Hebei Administration of Traditional Chinese Medicine","award":["206Z2501G"],"award-info":[{"award-number":["206Z2501G"]}]},{"name":"Scientific Research Project of Hebei Administration of Traditional Chinese Medicine","award":["20372502D"],"award-info":[{"award-number":["20372502D"]}]},{"name":"Scientific Research Project of Hebei Administration of Traditional Chinese Medicine","award":["H2019423050"],"award-info":[{"award-number":["H2019423050"]}]},{"name":"Scientific Research Project of Hebei Administration of Traditional Chinese Medicine","award":["2021100"],"award-info":[{"award-number":["2021100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2021,12,22]]},"abstract":"<jats:p>As a classic TCM prescription, LGZG has been widely used in clinical prevention and treatment of heart failure, nonalcoholic fatty liver, and hyperlipidemia. However, there are few studies on chemical components in recent years, and the basis of quality evaluation is not sufficient. This study was to find the active ingredients of the Lingguizhugan decoction using UPLC-MS\/MS and network pharmacology. By comparing the retention time and MS dates of the reference and self-building database, the cleavage rules of chemical composition whose mass errors are less than 1\u2009ppm(FL less than 3\u2009ppm) are analyzed. On this basis, a network pharmacology method was used to find biomarkers for quantitative analysis. The results show that 149 compounds were preliminaries identified or inferred, including 63 flavonoids, 30 triterpenes, 22 phenylpropanoids, 13 organic acids, 6 lactones, 5 alkaloids, 4 anthraquinones, and 6 other compounds. According to the network pharmacology results, 20 chemical constituents were selected as the biomarkers, which were determined simultaneously for the first time, including poricoic acid A, poricoic acid B, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, isoliquiritin, liquiritigenin, isoliquiritin apioside, cinnamic acid, caffeic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid A, B, and C, atractylenolide I, II, and III, and coumarin. The methodological results show that the linearity, stability, precision, repeatability, and recovery of the method are satisfactory. Therefore, a comprehensive quality assessment system for LGZG was established on the basis of a systematic study of chemical substances and network pharmacology, which provided an important reference for the foundation of pharmacological action and its mechanics.<\/jats:p>","DOI":"10.1155\/2021\/7849032","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T23:05:10Z","timestamp":1640214310000},"page":"1-19","source":"Crossref","is-referenced-by-count":14,"title":["Phytochemical Analysis Using UPLC-MS\/MS Combined with Network Pharmacology Methods to Explore the Biomarkers for the Quality Control of Lingguizhugan Decoction"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8917-1687","authenticated-orcid":true,"given":"Baolin","family":"Li","sequence":"first","affiliation":[{"name":"College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"},{"name":"Hebei Traditional Chinese Medicine Formula Granule Engineering & Technology Innovate Center, Shijiazhuang 050091, China"},{"name":"Quality Evaluation & Standardization Hebei Province Engineering Research Center of Traditional Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-7661","authenticated-orcid":true,"given":"Shuaishuai","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-2913","authenticated-orcid":true,"given":"Jingnan","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0023-6745","authenticated-orcid":true,"given":"Yongben","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4143-8119","authenticated-orcid":true,"given":"Yu","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-9383","authenticated-orcid":true,"given":"Fengxia","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2886-6941","authenticated-orcid":true,"given":"Xinguo","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"},{"name":"Hebei Traditional Chinese Medicine Formula Granule Engineering & Technology Innovate Center, Shijiazhuang 050091, China"},{"name":"Quality Evaluation & Standardization Hebei Province Engineering Research Center of Traditional Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3779-097X","authenticated-orcid":true,"given":"Liying","family":"Niu","sequence":"additional","affiliation":[{"name":"College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"},{"name":"Hebei Traditional Chinese Medicine Formula Granule Engineering & Technology Innovate Center, Shijiazhuang 050091, China"},{"name":"Quality Evaluation & Standardization Hebei Province Engineering Research Center of Traditional Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"issue":"1","key":"1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1186\/s12906-019-2771-6","article-title":"Lingguizhugan decoction attenuates doxorubicin-induced heart failure in rats by improving TT-SR microstructural remodeling","volume":"19","author":"X. Li","year":"2019","journal-title":"BMC Complementary and Alternative Medicine"},{"key":"2","doi-asserted-by":"crossref","first-page":"918","DOI":"10.3389\/fphys.2019.00918","article-title":"Linggui zhugan formula improves glucose and lipid levels and alters gut microbiota in high-fat diet-induced diabetic mice","volume":"10","author":"R. Wu","year":"2019","journal-title":"Frontiers in Physiology"},{"issue":"36","key":"3","first-page":"2867","article-title":"Protective effects of Lingguizhugan decoction on amyloid-beta peptide (25-35)-induced cell injury: anti-inflammatory effects","volume":"7","author":"F. Xi","year":"2012","journal-title":"Neural Regeneration Research"},{"key":"4","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2019.112397","article-title":"Integrative serum metabolomics and network analysis on mechanisms exploration of Ling-Gui-Zhu-Gan Decoction on doxorubicin-induced heart failure mice","volume":"250","author":"X. Wang","year":"2020","journal-title":"Journal of Ethnopharmacology"},{"issue":"5","key":"5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s11655-018-3024-0","article-title":"Linggui zhugan decoction () inhibits ventricular remodeling after acute myocardial infarction in mice by suppressing TGF-\u03b2(1)\/smad signaling pathway","volume":"26","author":"L. Wang","year":"2020","journal-title":"Chinese Journal of Integrative Medicine"},{"issue":"1","key":"6","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1186\/s13063-020-04362-7","article-title":"Traditional Chinese medicine Lingguizhugan decoction treating non-alcoholic fatty liver disease with spleen-yang deficiency pattern: study protocol for a multicenter randomized controlled trial","volume":"21","author":"J. Xu","year":"2020","journal-title":"Trials"},{"issue":"27","key":"7","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.3748\/wjg.v25.i27.3590","article-title":"Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota","volume":"25","author":"M. T. Liu","year":"2019","journal-title":"World Journal of Gastroenterology"},{"issue":"1","key":"8","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s12906-017-1557-y","article-title":"Modified lingguizhugan decoction incorporated with dietary restriction and exercise ameliorates hyperglycemia, hyperlipidemia and hypertension in a rat model of the metabolic syndrome","volume":"17","author":"L. Yao","year":"2017","journal-title":"BMC Complementary and Alternative Medicine"},{"key":"9","article-title":"Clinical efficacy of Linggui Zhugan decoction in the treatment of decreased gastric motility caused by chronic heart failure","author":"X. Hou","year":"2021","journal-title":"Minerva Medica"},{"issue":"16","key":"10","doi-asserted-by":"crossref","first-page":"e25563","DOI":"10.1097\/MD.0000000000025563","article-title":"Linggui Zhugan Decoction for peripheral vertigo: a protocol for systematic review and meta-analysis","volume":"100","author":"H. Ma","year":"2021","journal-title":"Medicine (Baltimore)"},{"key":"11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.compbiomed.2019.05.007","article-title":"Network pharmacology-based identification for therapeutic mechanism of Ling-Gui-Zhu-Gan decoction in the metabolic syndrome induced by antipsychotic drugs","volume":"110","author":"S. Y. Xiang","year":"2019","journal-title":"Computers in Biology and Medicine"},{"issue":"11","key":"12","first-page":"1371","article-title":"Chemical profile Analysis of ling-gui-zhu-Gan decoction by LC\u2013QTOF MS and simultaneous determination of nine major components using QAMS method","volume":"83","author":"X. Y. Li","year":"2019","journal-title":"Chromatographia"},{"key":"13","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.talanta.2018.08.020","article-title":"LC-ESI-MS\/MS method for simultaneous determination of eleven bioactive compounds in rat plasma after oral administration of Ling-Gui-Zhu-Gan Decoction and its application to a pharmacokinetics study","volume":"190","author":"B. Ji","year":"2018","journal-title":"Talanta"},{"issue":"4","key":"14","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/pca.3007","article-title":"Rapid classification and identification of chemical constituents in Epimedium koreanum Nakai by UPLC-Q-TOF-MS combined with data post-processing techniques","volume":"32","author":"N. Li","year":"2021","journal-title":"Phytochemical Analysis"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2793058"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9915027"},{"issue":"14","key":"17","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1080\/14786419.2019.1569013","article-title":"Identification and quantification of main flavonoids in the leaves of Bambusa multiplex cv. Fernleaf","volume":"34","author":"X. L. Qiu","year":"2020","journal-title":"Natural Product Research"},{"issue":"10","key":"18","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1615\/IntJMedMushrooms.2018027398","article-title":"Identification and quantification of triterpenoids in lingzhi or reishi medicinal mushroom, ganoderma lucidum (agaricomycetes), with HPLC-MS\/MS methods","volume":"20","author":"H. Xin","year":"2018","journal-title":"International Journal of Medicinal Mushrooms"},{"key":"19","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2021.111735","article-title":"Systematic investigation of the pharmacological mechanism for renal protection by the leaves of Eucommia ulmoides Oliver using UPLC-Q-TOF\/MS combined with network pharmacology analysis","volume":"140","author":"Q. Huang","year":"2021","journal-title":"Biomedicine & Pharmacotherapy"},{"issue":"6","key":"20","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/pca.2963","article-title":"Chemical characterisation and quantification of the major constituents in the Chinese herbal formula Jian-Pi-Yi-Shen pill by UPLC-Q-TOF-MS\/MS and HPLC-QQQ-MS\/MS","volume":"31","author":"F. Wang","year":"2020","journal-title":"Phytochemical Analysis"},{"key":"21","article-title":"Mori ramulus (Chin.Ph.)-the dried twigs of morus alba L.\/Part 1: discovery of two novel coumarin glycosides from the anti-hyperuricemic ethanol extract","volume":"24","author":"J. Yao","year":"2019","journal-title":"Molecules"},{"key":"22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jpba.2018.03.005","article-title":"Chemical profiling and quantitation of bioactive compounds in Platycladi Cacumen by UPLC-Q-TOF-MS\/MS and UPLC-DAD","volume":"154","author":"B. Zhuang","year":"2018","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"issue":"7","key":"23","doi-asserted-by":"crossref","first-page":"e4829","DOI":"10.1002\/bmc.4829","article-title":"Analysis of chemical constituents and six compounds in Qu-feng-sheng-shi Granules via HPLC-ESI-Q\/TOF-MS(n) and HPLC-UV technique","volume":"34","author":"P. Yang","year":"2020","journal-title":"Biomedical Chromatography"},{"issue":"5","key":"24","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1002\/pca.3029","article-title":"Cleavage rules of mass spectrometry fragments and rapid identification of chemical components of Radix Paeoniae Alba using UHPLC-Q-TOF-MS","volume":"32","author":"S. Yang","year":"2021","journal-title":"Phytochemical Analysis"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5546446"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8861765"},{"key":"27","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpba.2021.114229","article-title":"Identification and characterization of quinoline alkaloids from the root bark of Dictamnus dasycarpus and their metabolites in rat plasma, urine and feces by UPLC\/Qtrap-MS and UPLC\/Q-TOF-MS","volume":"204","author":"K. Chang","year":"2021","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"key":"28","article-title":"Global identification and quantitative analysis of representative components of Xin-Nao-Kang Capsule, a traditional Chinese medicinal formula, by UHPLC-Q-TOF-MS and UHPLC-TQ-MS","volume":"198","author":"Z. Ji","year":"2021","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"issue":"10","key":"29","doi-asserted-by":"crossref","first-page":"e4627","DOI":"10.1002\/jms.4627","article-title":"Method for rapidly discovering active components in Yupingfeng granules by UPLC-ESI-Q-TOF-MS","volume":"55","author":"M. Li","year":"2020","journal-title":"Journal of Mass Spectrometry"},{"key":"30","article-title":"Characterization of chemical profile and quantification of representative components of DanLou tablet, a traditional Chinese medicine prescription, by UHPLC-Q\/TOF-MS combined with UHPLC-TQ-MS","volume":"180","author":"P. Lin","year":"2020","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"issue":"2","key":"31","doi-asserted-by":"crossref","first-page":"e4401","DOI":"10.1002\/bmc.4401","article-title":"Chemical profiling by LC-MS\/MS and HPLC fingerprint combined with chemometrics and simultaneous determination of 16 characteristic ingredients for the quality consistency evaluation of Shaoyao-Gancao Decoction","volume":"33","author":"P. Lu","year":"2019","journal-title":"Biomedical Chromatography"},{"key":"32","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jchromb.2018.10.011","article-title":"A UHPLC-QTOF-MS\/MS method for the simultaneous determination of eight triterpene compounds from Poria cocos (Schw.) Wolf extract in rat plasma: application to a comparative pharmacokinetic study","volume":"1102-1103","author":"Q. Qian","year":"2020","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"33","doi-asserted-by":"crossref","first-page":"114267","DOI":"10.1016\/j.jpba.2021.114267","article-title":"Simultaneous determination of twenty-five compounds with anti-inflammatory activity in Spatholobi Caulis by using an optimized UFLC-MS\/MS method: an application to pharmacokinetic study","volume":"204","author":"X. Y. Liu","year":"2021","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"key":"34","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.phymed.2018.09.002","article-title":"Pharmacokinetics study of 16 representative components from Baoyuan Decoction in rat plasma by LC-MS\/MS with a large-volume direct injection method","volume":"57","author":"Y. Y. Lu","year":"2019","journal-title":"Phytomedicine"},{"issue":"7","key":"35","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1080\/14786419.2019.1641808","article-title":"Simultaneous determination of multiple components in formula and preparations of Xiaoyaosan","volume":"35","author":"H. Su","year":"2019","journal-title":"Natural Product Research"},{"key":"36","article-title":"Simultaneous determination of six components of Danzhi Xiaoyao Pill in beagle plasma by HPLC-MS\/MS and a study of pharmacokinetic of paeoniflorin and geniposide after single-dose administration","volume":"186","author":"Y. L. Zhu","year":"2019","journal-title":"Journal of Pharmaceutical and Biomedical Analysis"},{"issue":"11","key":"37","doi-asserted-by":"crossref","first-page":"e4334","DOI":"10.1002\/bmc.4334","article-title":"Pharmacokinetics of Sijunzi decoction in rat plasma after oral administration using ultra-high-performance liquid chromatography electrospray ionization quadrupole-time of flight mass spectrometry","volume":"32","author":"G. Qu","year":"2019","journal-title":"Biomedical Chromatography"}],"container-title":["Evidence-Based Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/7849032.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/7849032.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ecam\/2021\/7849032.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T23:05:48Z","timestamp":1640214348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ecam\/2021\/7849032\/"}},"subtitle":[],"editor":[{"given":"Nahla S.","family":"Abdel Azim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":37,"alternative-id":["7849032","7849032"],"URL":"https:\/\/doi.org\/10.1155\/2021\/7849032","relation":{},"ISSN":["1741-4288","1741-427X"],"issn-type":[{"value":"1741-4288","type":"electronic"},{"value":"1741-427X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,12,22]]}}}