Wang Beizhi, Huang Yumeng, Ding Youjun, Chen Jingyi, Chen Yutong, Zhang Hao, Tan Qian
Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College Nanjing University of Chinese Medicine Nanjing China.
Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Clinical College Jiangsu University Nanjing China.
Food Sci Nutr. 2025 Aug 1;13(8):e70688. doi: 10.1002/fsn3.70688. eCollection 2025 Aug.
Diabetic wounds that do not heal are a significant complication of diabetes, among which chronic inflammation serves as a critical contributing factor. The regulation of inflammation in diabetic wound healing is significantly impacted by macrophages via their efferocytosis and polarization activities. Naringenin is a natural flavonoid that has been recognized for its anti-inflammatory effects and potential therapeutic benefits in treating diabetes-related conditions. This research examines how naringenin impacts non-healing diabetic wounds and delves into the mechanisms behind it. The study involved male C57BL/6 mice categorized into three groups: control, diabetes, and diabetes with naringenin treatment. Researchers assessed the effect of naringenin on wound healing by applying it topically to a diabetic mouse model induced with streptozotocin (STZ). Moreover, researchers used THP-1 cells in vitro to examine the effects of naringenin on the polarization of macrophages to the M2 phenotype and their efferocytosis. Subsequently, the effects of naringenin treatment were assessed using RT-qPCR, western blot, immunofluorescence, and additional assays. Animal experiments demonstrated that naringenin significantly accelerated diabetic wound healing. Naringenin decreased inflammatory cytokines, promoted M2 macrophage polarization, and enhanced macrophage efferocytosis in wound healing. Consistent with animal studies, naringenin inhibits macrophage M1 polarization while augmenting M2 polarization in THP-1 cells, with ML385 specifically rescuing the M1 suppression. In addition, naringenin also promoted macrophage efferocytosis in a THP-1/Jurkat apoptotic co-culture mode. Naringenin significantly promotes diabetic wound healing via ameliorating wound inflammation and exerts its therapeutic effects through promoting M2 macrophages and enhancing efferocytosis.
无法愈合的糖尿病伤口是糖尿病的一种严重并发症，其中慢性炎症是一个关键的促成因素。巨噬细胞通过其吞噬凋亡细胞作用和极化活动，对糖尿病伤口愈合过程中的炎症调节产生显著影响。柚皮素是一种天然黄酮类化合物，其抗炎作用以及在治疗糖尿病相关病症方面的潜在治疗益处已得到认可。本研究探讨了柚皮素如何影响不愈合的糖尿病伤口，并深入研究其背后的机制。该研究涉及将雄性C57BL/6小鼠分为三组：对照组、糖尿病组和柚皮素治疗的糖尿病组。研究人员通过将柚皮素局部应用于链脲佐菌素（STZ）诱导的糖尿病小鼠模型，评估了其对伤口愈合的影响。此外，研究人员在体外使用THP-1细胞，研究柚皮素对巨噬细胞向M2表型极化及其吞噬凋亡细胞作用的影响。随后，使用RT-qPCR、蛋白质免疫印迹、免疫荧光和其他检测方法评估柚皮素治疗的效果。动物实验表明，柚皮素显著加速了糖尿病伤口的愈合。柚皮素减少了炎症细胞因子，促进了M2巨噬细胞极化，并增强了伤口愈合过程中的巨噬细胞吞噬凋亡细胞作用。与动物研究一致，柚皮素在THP-1细胞中抑制巨噬细胞M1极化，同时增强M2极化，ML385可特异性挽救M1抑制。此外，柚皮素还在THP-1/ Jurkat凋亡共培养模式下促进了巨噬细胞吞噬凋亡细胞作用。柚皮素通过改善伤口炎症显著促进糖尿病伤口愈合，并通过促进M2巨噬细胞和增强吞噬凋亡细胞作用发挥其治疗效果。
