(-)-Epicatechin Protects against Fatty Liver Hemorrhagic Syndrome in Laying Hens by Integrating Multitarget Mechanisms via ERα Signaling

  • J Agric Food Chem. 2026 Jun 17;74(23):18051-18071. doi: 10.1021/acs.jafc.6c04072.
Yulei Wang  1  2 ,  Ping Gong  1  2 ,  Shujuan Zhao  1  2 ,  Fuya He  1  2 ,  Haitian Ma  1  2
Affiliations
  • 1. Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
  • 2. MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
PMID: 42231735 DOI: 10.1021/acs.jafc.6c04072
Abstract

Fatty liver hemorrhagic syndrome (FLHS) is a common metabolic disorder in laying hens with limited preventive strategies. This study evaluated whether (-)-epicatechin (EC) protects against FLHS induced by a high-energy, low-protein diet. EC supplementation alleviated hepatic lipid accumulation, dyslipidemia, liver injury, oxidative stress, inflammation, and Apoptosis. Network pharmacology identified Estrogen receptor α (ERα) as a core target, and molecular docking predicted EC binding to the ERα Ligand cavity. In vivo and in vitro validation confirmed an ERα-dependent mechanism: EC-activated ERα reprogrammed lipid metabolism, suppressed the HIF-1α pathway to enhance antioxidant capacity, and inhibited Src kinase to block NF-κB and MAPK signaling, thereby reducing inflammation and Apoptosis. These findings demonstrate that EC counteracts FLHS through an ERα-centered multitarget mechanism, supporting its potential as a dietary supplement for managing FLHS in poultry.

Keywords
(−)-epicatechin; ERα signaling pathway; fatty liver hemorrhagic syndrome; molecular docking; network pharmacology.
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