Kaempferol Protects Against Hindlimb Ischemia‐Reperfusion Injury via Activation of PPARα Signaling

作者：Yue-He Liu, Muliang Lin, Hong Qian, Weiwei Wang, Tao Yuan, Zheng-Kai Ren, Jianlun Hu, Yang Wang, Guoyin Liu, Zhong-Yang Sun, Peng Gou, Zhao-Rui Sun, Yuan-Yuan Chen, Yan Sun, Yunfei He, Xin Yu, Shinan Nie · 发表于：Journal of biochemical and molecular toxicology · 年份：2026 · DOI：10.1002/jbt.70914 · 研究领域：Medicine

Limb ischemia‐reperfusion (I/R) injury is a life‐threatening complication of acute limb ischemia that can result in severe skeletal muscle damage and limb loss, yet effective pharmacological therapies remain limited. Kaempferol (KAE), a naturally occurring dietary flavonoid with well‐documented anti‐inflammatory, antioxidant, and anti‐apoptotic properties, has been shown to confer protection in myocardial and cerebral I/R models. Nevertheless, its therapeutic potential and molecular mechanisms in limb I/R injury have not yet been elucidated. In this study, we systematically investigated the protective effects and underlying mechanisms of KAE in a mouse hindlimb I/R model. A network pharmacology approach was initially applied to provide a global overview of potential biological processes associated with KAE treatment. The therapeutic efficacy and molecular mechanisms of KAE were subsequently evaluated using in vivo experiments combined with transcriptomic profiling. Mice subjected to 4 h of hindlimb ischemia followed by 24 h of reperfusion received KAE (50 or 100 mg/kg, intraperitoneally) for 7 consecutive days prior to I/R induction. KAE markedly improved hindlimb microcirculation, alleviated tissue edema and infarction, preserved muscle histological integrity, and attenuated elevations of circulating muscle injury biomarkers. In parallel, KAE significantly suppressed I/R‐induced oxidative stress, inflammatory infiltration, and apoptotic cell death, as evidenced by reduced RO...