Sepsis‐Induced Liver Injury Mitigated by Isoferulic Acid Through Inhibition of Hepatic Ferroptosis via the SIRT1 Signaling Pathway

作者：Jian Gan, Tong Xu, Jiayi Zhang, Can Huang, Yue Hua, Honglin Xu, Guoyong Zhang, Changlei Hu, Mingjie Pang, Bin Liu, Yingchun Zhou · 发表于：Phytotherapy Research · 年份：2025 · DOI：10.1002/ptr.70098 · 被引用次数：2 · 研究领域：Ferroptosis and cancer prognosis、Drug Transport and Resistance Mechanisms、Cancer, Lipids, and Metabolism

The liver plays a crucial role in the progression of sepsis in patients. Notably, it is the center of metabolism and detoxification, and is important for immune regulation and inflammatory response. Isoferulic acid (IFA), as a phenolic acid compound naturally found in Cimicifuga plants, is recognized for its anti-inflammatory, antioxidant, and free radical-scavenging properties. However, its protective mechanism underlying sepsis-induced acute liver injury remains unknown. The present work focused on examining the effect of IFA on treating sepsis-mediated liver injury and exploring its potential protective mechanism. In the in vivo experiments, the cecal ligation and puncture (CLP) model was used to induce sepsis in mice. EX-527 was administered through intraperitoneal injection, while IFA was given via intragastric administration. Thereafter, hepatic pathological damage was assessed through hematoxylin-eosin staining. Lipid peroxidation levels were determined by measuring MDA, SOD, GSH, and ferrous iron contents. Meanwhile, relevant gene and target protein levels were analyzed using qPCR, immunohistochemistry, and Western blotting. For the in vitro experiments, ferroptosis was induced in AML12 cells with erastin, followed by transfection with SIRT1-siRNA and treatment with IFA. Subsequently, ROS levels were systematically assessed, the extent of mitochondrial membrane potential (MMP) damage was quantified, and Nrf2 immunofluorescence staining analysis was performed in AML12 ...