Cyanidin-3-glucoside mitigates zearalenone-enhanced hepatic lipotoxicity via inhibition of PXR activation

  • Food Res Int. 2026 Sep 30:240:119687. doi: 10.1016/j.foodres.2026.119687.
Bingxin Huangfu  1 ,  Teng Wang  1 ,  Dongbao Cai  2 ,  Jia Xu  3 ,  Kunlun Huang  4 ,  Zhihong Liang  4 ,  Weibin Bai  2 ,  Xiaoyun He  5
Affiliations
  • 1. Key Laboratory of Precision Nutrition and Food Quality, Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
  • 2. Department of Food Science and Engineering, Institute of Food Safety and Nutrition, Jinan University, Guangzhou, 510632, PR China.
  • 3. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
  • 4. Key Laboratory of Precision Nutrition and Food Quality, Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China; Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), The Ministry of Agriculture and Rural Affairs of the PR China, Beijing, 100083, China.
  • 5. Key Laboratory of Precision Nutrition and Food Quality, Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China; Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), The Ministry of Agriculture and Rural Affairs of the PR China, Beijing, 100083, China. Electronic address: [email protected].
PMID: 42409506 DOI: 10.1016/j.foodres.2026.119687
Abstract

Zearalenone (ZEA) is a mycotoxin frequently detected in food. Cyanidin-3-glucoside (C3G), an anthocyanin abundant in food, exhibits regulatory effects on hepatic metabolism; however, its role in ZEA-induced hepatic lipotoxicity remains unclear. In this study, C57BL/6 J mice were exposed to low-dose ZEA (0.5 mg/kg·bw) combined with a combined with a high-fat diet (HFD) for 96 days, and HepG2 and HepaRG cells were treated with ZEA and oleic acid to investigate chronic ZEA-induced metabolic disturbances. C3G was administered to evaluate its protective effects. ZEA disrupted hepatic energy metabolism, promoted lipid accumulation, and induced more severe lipotoxicity. Mechanistically, ZEA activated the pregnane X receptor (PXR), upregulating fatty acid transporters CD36 and FABP4, thereby enhancing fatty acid uptake and lipid synthesis. C3G inhibits ZEA-induced PXR activation, thereby suppressing PXR signaling and alleviating ZEA-induced hepatic lipotoxicity under HFD conditions. Collectively, C3G mitigates ZEA-induced hepatic lipotoxicity by inhibiting PXR activation, highlighting anthocyanins as potential interventions against mycotoxin-associated metabolic injury.

Keywords
Anthocyanins; Cyanidin-3-O-glucoside; Metabolic associated fatty liver disease; Pregnane X receptor; Zearalenone.
Products