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Herbal weight loss supplements (WLS) are a group of HDS that are frequently implicated in cases of toxicity; however, the causative substances often remain unknown due to the complex chemical nature of such supplements. This study aimed to analyse the\n                    <jats:italic>in vitro<\/jats:italic>\n                    safety (in human liver carcinoma (HepG2) cells and colon carcinoma (Caco\u20102) cells) of 12 active compounds commonly found in WLS, first with safety screening using the MTT cytotoxicity assay, followed by metabolic profiling with\n                    <jats:sup>1<\/jats:sup>\n                    H NMR spectroscopy. Of the phytochemicals evaluated, epigallocatechin\u20103,0\u2010gallate (EGCG) was the only compound that caused a significant reduction in the viability of both cell lines (25.3% in HepG2 cells and 18.5% in Caco\u20102 cells), and this decrease was potentiated by CYP450 induction with rifampicin. Subsequent\n                    <jats:sup>1<\/jats:sup>\n                    H NMR analysis showed changes in key metabolites such as amines, amino acids, carboxylic acids, and glucose that were indicative of protein degradation and disrupted energy and lipid metabolism. While the remaining 11 active compounds analysed did not demonstrate significant toxicity in isolation, these require further assessment to determine their safety when used in combination with other phytochemicals. Given that the majority of WLS contain multiple herbal ingredients, each with a complex chemical composition, it is important to understand the role of interactions in adverse events.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70170","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T21:40:16Z","timestamp":1765316416000},"page":"906-920","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of\n                    <i>in vitro<\/i>\n                    toxicity of common phytochemicals included in weight loss supplements using\n                    <scp>\n                      <sup>1<\/sup>\n                      H NMR\n                    <\/scp>\n                    spectroscopy"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-8395","authenticated-orcid":false,"given":"Emily C.","family":"Davies","sequence":"first","affiliation":[{"name":"Centre for Computational and Systems Medicine Murdoch University  Perth Australia"},{"name":"Medical, Molecular and Forensic Sciences Murdoch University  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth L.","family":"Maker","sequence":"additional","affiliation":[{"name":"Centre for Computational and Systems Medicine Murdoch University  Perth Australia"},{"name":"Medical, Molecular and Forensic Sciences Murdoch University  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1016-0588","authenticated-orcid":false,"given":"Ian F.","family":"Musgrave","sequence":"additional","affiliation":[{"name":"Adelaide Medical School The University of Adelaide  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9193-0462","authenticated-orcid":false,"given":"Samantha","family":"Lodge","sequence":"additional","affiliation":[{"name":"Centre for Computational and Systems Medicine Murdoch University  Perth Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phanu.2021.100282"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2021.100539"},{"key":"e_1_2_11_4_1","unstructured":"(2025)Dietary supplements: what you need to know. [cited 2025 Oct 8]. Available from:https:\/\/ods.od.nih.gov\/factsheets\/WYNTK\u2010Consumer\/"},{"key":"e_1_2_11_5_1","unstructured":"Therapeutic Goods Administration(2023)Complementary medicines. [cited 2025 Oct 8]. Available from:https:\/\/www.tga.gov.au\/products\/medicines\/non\u2010prescription\u2010medicines\/complementary\u2010medicines"},{"key":"e_1_2_11_6_1","unstructured":"Human Food Program (HFP) FY(2025)Priority deliverables. [cited 2025 Oct 8]. Available from:https:\/\/www.fda.gov\/about\u2010fda\/human\u2010foods\u2010program\/human\u2010food\u2010program\u2010hfp\u2010fy\u20102025\u2010priority\u2010deliverables"},{"key":"e_1_2_11_7_1","unstructured":"(2025)Registered complementary medicines. [cited 2025 Oct 8]. 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