Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

• Published in: Hepatobiliary & pancreatic diseases international Vol. 23; no. 1; pp. 25 - 34
• Main Authors: Bao, Hai-Li, Chen, Chuan-Zhi, Ren, Chang-Zhen, Sun, Ke-Yan, Liu, Hao, Song, Shao-Hua, Fu, Zhi-Ren
• Format: Journal Article
• Language: English
• Published: Singapore Elsevier B.V 01.02.2024; Department of Organ Transplantation,Shanghai Changzheng Hospital,Navy Military Medical University,Shanghai 200003,China%Department of Surgical Oncology,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China%Department of Cardiology,Shanghai Changzheng Hospital,Naval Military Medical University,Shanghai 200003,China%Department of General Surgery,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China
• Subjects: Animals; Apoptosis; Glucosides - metabolism; Glucosides - pharmacology; Hepatic ischemia-reperfusion injury; Inflammation; Liver - pathology; Macrophage; Macrophages - metabolism; Mice; NF-kappa B - metabolism; Oxidative Stress; Polarization; Polydatin; Reperfusion Injury - pathology; Polarization; Inflammation; Hepatic ischemia-reperfusion injury; Polydatin; Macrophage
• ISSN: 1499-3872
• DOI: 10.1016/j.hbpd.2022.08.009

Polydatin, a glucoside of resveratrol, has shown protective effects against various diseases. However, little is known about its effect on hepatic ischemia-reperfusion (I/R) injury. This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism. After gavage feeding polydatin once daily for a week, mice underwent a partial hepatic I/R procedure. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hematoxylin-eosin (H&E) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response and reactive oxygen species (ROS) production was also investigated. Furthermore, immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages. Compared with the I/R group, polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis. The oxidative stress marker (dihydroethidium fluorescence, malondialdehyde, superoxide dismutase and glutathione peroxidase) and I/R related inflammatory cytokines (interleukin-1β, interleukin-10 and tumor necrosis factor-α) were significantly suppressed after polydatin treatment. In addition, the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro. Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway. Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NF-κB signaling.