{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T17:02:01Z","timestamp":1772470921050,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFF1106702"],"award-info":[{"award-number":["2024YFF1106702"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: There is high demand for Anshenbunao syrup (ABS) in Chinese medicine owing to its steady therapeutic efficacy for insomnia and neurasthenia. However, it contains a substantial proportion of Polygoni Multiflori Radix Praeparata (PMRP), which is associated with reported cases of drug-induced liver injury (DILI). Here, we aim to establish an integrated approach combining PK screening with a dual-model toxicity verification system to systematically identify liver injury components (from high to low concentrations and from direct to idiosyncratic hepatotoxicity) to accurately uncover diverse potential hepatotoxicity markers. Methods: A sensitive UPLC-MS\/MS method was used to accurately quantify the components in plasma at the ng\/mL level and conduct a pharmacokinetic analysis. Rat models were used to evaluate exposure levels of the eight active constituents and three major metabolites after a single oral gavage dose of 10 mL\/kg ABS and identify the quality markers. The early-stage and high-throughput assessment of direct and idiosyncratic hepatotoxicity was conducted in vitro utilizing HepG2 cells. After the administration of the quality markers (0.01\u201380 \u03bcM), CCK-8 was used to detect cell viability on both normal and susceptible cells, and the latter was induced by lipopolysaccharide. Results: As a result, seven quality markers were screened based on their contents and exposure levels in rat plasma by UPLC\u2013MS\/MS, including emodin (EM), liquiritin (LI), 2,3,5,4\u2032\u2013Tetrahydroxystilbene\u20132\u2013O\u2013\u03b2\u2013D\u2013glucoside (TSG), icariin, emodin\u20138\u2013O\u2013\u03b2\u2013D\u2013glucoside, baohuoside I (BA), and 18\u03b2\u2013glycyrrhetinic acid (GTA). Moreover, the half maximal inhibitory concentration values of both normal cells and the lipopolysaccharide-induced immune stress liver injury cells were fitted within the concentration range of 0.01\u201380 \u03bcM, based on which, EM, BA, and GTA were identified as the principal hepatotoxic constituents in ABS at elevated concentrations. This study is the first to demonstrate that TSG, EM, LI, and GTA exhibit synergistic cytotoxicity in LPS-sensitized hepatocytes at clinically relevant concentrations, whereas EM was also a direct hepatotoxic component. Given that TSG is one of the major ingredients in ABS, the underappreciated idiosyncratic hepatotoxicity could elevate the risk of adverse clinical outcomes. Conclusions: In conclusion, this study effectively identifies hepatotoxic constituents in ABS and evaluates their hazards under immune stress and toxicity profiles in clinical concentrations, which also provides a robust foundation for the awareness of PMRP-induced DILI due to ABS.<\/jats:p>","DOI":"10.3390\/ph19030404","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatotoxicity Assessment of Anshenbunao Syrup by Multi-Component Quantification In Vivo\/In Vitro and Cell Biological Evaluations"],"prefix":"10.3390","volume":"19","author":[{"given":"Lan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhizhen","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5134-6228","authenticated-orcid":false,"given":"Pengwei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shixiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adouani","family":"Imene","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Ferhat Abbas Setif 1, Setif 19000, Algeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3225-2769","authenticated-orcid":false,"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Shenyang 110122, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengming","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Food Safety, Chinese Academy of Quality and Inspection & Testing, Beijing 100176, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taijun","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"116754","DOI":"10.1016\/j.biopha.2024.116754","article-title":"Neuroprotective effects of Anshen Bunao Syrup on cognitive dysfunction in Alzheimer\u2019s disease rat models","volume":"176","author":"Sun","year":"2024","journal-title":"Biomed. 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