Narirutin treatment accelerates the process of diabetic wound repair by regulating phenotype switching of macrophages through affecting metabolic reprogramming

作者：Liang Liu, Han Wang, Juan Zhou, Jing Lu, Yan Zhang, Haiyan Liu, Li Lü · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1614967 · 被引用次数：5 · 研究领域：Wound Healing and Treatments、Immune cells in cancer、Mangiferin and Mango Extracts

Introduction: Diabetic foot ulcer (DFU) is one of the most common complications of diabetes, with substantial morbidity and mortality. Narirutin (Nar), a bioactive phytochemical derived from citrus peel, has been suggested to possess anti-inflammatory abilities. However, the involvement of Nar in DFU development remains poorly understood. Methods: The polarization traits of bone marrow derived macrophages (BMDMs) with indicated treatments were determined by flow cytometry, immunofluorescence staining, western blot and qRT-PCR. Levels of lactate and α-ketoglutarate were measured for investigating the metabolic profiles. The cutaneous wounds of diabetic mice were established for evaluating the promotive roles of Nar in wound healing Results: We found that high glucose treatment significant elevated the contents of TNF-α and IL-1β and lactate and reduced the levels of TGF-β1 and IL-4 and α-ketoglutarate in BMDMs. Then, Nar intervention effectively induced BMDMs repolarization from M1 to M2 state and the molecular mechanism was ascribed to drug-elicited activation of AMPK, which in turn increased the expression of downstream Mfn2, thereby enhancing the activity of oxidative phosphorylation and GATA3 cascade activation and disrupting the progress of glycolysis and NF-κB axis activation. Subsequently, we discovered that Nar injection effectively enhanced the healing rate of skin wounds in diabetic mice. Histological analysis showed that Nar dose-dependently induced dermis growth an...