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Updated: Jan 14, 2026

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Hepatic and Renal Toxicity of Gardenia Yellow: Repeated-Dose Assessment and Human Oral Equivalent Dose Prediction via
Yue-Fei Lai1, Fei-Fei Xu1, Wei-Liang Wu1
1Food Safety and Health Research Center, NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Guangdong-Hongkong-Macao Joint Laboratory for Contaminants Exposure and Health, School of Public Health, Southern Medical University, Guangzhou 510515, P. R. China.
Abstract:
Gardenia yellow, an edible pigment derived from Gardenia jasminoides, has wide food applications; however, its safety profile is insufficiently defined. In this study, we characterized the composition of gardenia yellow and simulated its gastrointestinal digestion, absorption, and metabolism using an in vitro gastrointestinal model. Its hepatotoxicity and nephrotoxicity were assessed using the HepaRG and RPTEC/TERT1 cell lines via cellular viability, oxidative stress, and mitochondrial dysfunction assays. Its lowest effective concentration (LEC), determined after 14 days of repeated exposure, was used to estimate its oral equivalent dose (OED) via the in vitro-to-in vivo extrapolation (IVIVE) method. Crocin, the primary bioactive component of gardenia yellow (44.96%), exhibited 4.68 ± 1.00% oral bioavailability and was biotransformed to crocetin (30.47 ± 1.95%) in the colon. Crocetin induced oxidative stress and mitochondrial dysfunction in hepatic and renal cells. The predicted oral equivalent dose for gardenia yellow (1.43 g/(kg·bw·day)) exceeded the typical Chinese dietary exposure, indicating a favorable safety margin.
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