{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:41:32Z","timestamp":1761198092300,"version":"build-2065373602"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Ethnopharmacological relevance<\/jats:title>\n                    <jats:p>\n                      The toxicity of\n                      <jats:italic>Polygonum multiflorum<\/jats:italic>\n                      (PM) is widely recognized. However, its toxic constituents and the mechanisms underlying their interactions remain insufficiently characterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aims to establish a new evaluation model that integrates multiparameter chemometric analysis with combined statistical approaches to assess and monitor the toxicity of PM. The multi-index framework included crude drug morphological traits, main chemical constituents (anthraquinones, stilbene glycosides, flavonoids and phenols), and hepatotoxicity across different PM batches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      An ultra-performance liquid chromatography\u2013electrospray ionization\u2013triple-quadrupole tandem mass spectrometry (UPLC-ESI-QqQ-MS\/MS) method was first developed to quantify 26 compounds in 61 batches of commercial PM samples. Chemometric analyses, including principal component analysis (PCA) and hierarchical cluster analysis (HCA), were then applied to classify the samples into four groups based on chemical composition. Hepatotoxicity comparisons among these groups were conducted using the Cell Counting Kit-8 assay in HepaRG cells. Subsequently, toxicity-related morphological traits were investigated by quantifying chromaticity values of crude drugs from groups with distinct toxicity profiles. Two key between-group toxicity variables were identified through chemometric analyses, including orthogonal partial least squares discriminant analysis (OPLS-DA) and\n                      <jats:italic>t<\/jats:italic>\n                      -tests. Systematic correlations between toxicity-related morphological traits and chemical composition were then established. Finally, emodin-8-\n                      <jats:italic>O<\/jats:italic>\n                      -\u03b2-\n                      <jats:italic>D<\/jats:italic>\n                      -glucoside (EG) and 2,3,5,4\u2032-tetrahydroxystilbene-2-\n                      <jats:italic>O<\/jats:italic>\n                      -\u03b2-\n                      <jats:italic>D<\/jats:italic>\n                      -glucopyranoside (THSG), the two most abundant and distinctive components, were co-administered to explore potential toxic interactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The established chemical profiling library of PM demonstrated a strong correlation with hepatocytotoxicity. White decoction pieces of PM were found to be safer, while THSG and EG were identified as potential hepatotoxic constituents. Moreover, THSG enhanced the hepatotoxicity of EG, indicating a synergistic effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The proposed model offers a novel framework linking morphological traits, chemical composition, and hepatotoxicity of PM, offering a reference for the safety evaluation of other medicinal herbs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1666300","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:35:57Z","timestamp":1761197757000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated chemometric evaluation of morphological traits, chemical composition, and hepatotoxicity of Polygonum multiflorum"],"prefix":"10.3389","volume":"16","author":[{"given":"Yanyi","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanrong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1124\/dmd.105.006759","article-title":"Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells","volume":"34","author":"Aninat","year":"2006","journal-title":"Drug Metab. 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