Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong 999077, China.
Int J Mol Sci. 2024 Oct 18;25(20):11197. doi: 10.3390/ijms252011197.
Inflammation in macrophages is exacerbated under hyperglycemic conditions, contributing to chronic inflammation and impaired wound healing in diabetes. This study investigates the potential of mangiferin, a natural polyphenol, to alleviate this inflammatory response by targeting a redox-sensitive transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2). Mangiferin, a known Nrf2 activator, was evaluated for its ability to counteract the hyperglycemia-induced inhibition of Nrf2 and enhance antioxidant defenses. The protective effects of mangiferin on macrophages in a hyperglycemic environment were assessed by examining the expression of Nrf2, NF-κB, NLRP3, HO-1, CAT, COX-2, IL-6, and IL-10 through gene and protein expression analyses using qPCR and immunoblotting, respectively. The mangiferin-mediated nuclear translocation of Nrf2 was evidenced, leading to a robust antioxidant response in macrophages exposed to a hyperglycemic microenvironment. This activation suppressed NF-κB signaling, reducing the expression of pro-inflammatory mediators such as COX-2 and IL-6. Additionally, mangiferin decreased NLRP3 inflammasome activation and reactive oxygen species accumulation in hyperglycemia exposed macrophages. Our findings revealed that mangiferin alleviated hyperglycemia-induced reductions in AKT phosphorylation, highlighting its potential role in modulating key signaling pathways. Furthermore, mangiferin significantly enhanced the invasiveness and migration of macrophages in a hyperglycemic environment, indicating its potential to improve wound healing. In conclusion, this study suggests that mangiferin may offer a promising therapeutic approach for managing inflammation and promoting wound healing in diabetic patients by regulating Nrf2 activity in hyperglycemia-induced macrophages.
在高血糖条件下，巨噬细胞中的炎症加剧，导致糖尿病中慢性炎症和受损的伤口愈合。本研究调查了芒果苷作为一种天然多酚，通过靶向一个氧化还原敏感的转录因子核因子红细胞 2 相关因子 2 (Nrf2)，减轻这种炎症反应的潜力。芒果苷，一种已知的 Nrf2 激活剂，评估了其对抗高血糖诱导的 Nrf2 抑制和增强抗氧化防御的能力。通过使用 qPCR 和免疫印迹分别检查 Nrf2、NF-κB、NLRP3、HO-1、CAT、COX-2、IL-6 和 IL-10 的基因和蛋白表达分析，评估了芒果苷在高血糖环境下对巨噬细胞的保护作用。证明了芒果苷介导的 Nrf2 核易位，导致暴露于高血糖微环境中的巨噬细胞产生强大的抗氧化反应。这种激活抑制了 NF-κB 信号通路，降低了 COX-2 和 IL-6 等促炎介质的表达。此外，芒果苷还降低了高糖暴露的巨噬细胞中 NLRP3 炎性小体的激活和活性氧的积累。我们的研究结果表明，芒果苷减轻了高血糖诱导的 AKT 磷酸化减少，突出了其在调节关键信号通路中的潜在作用。此外，芒果苷显著增强了高糖环境中巨噬细胞的侵袭和迁移能力，表明其有潜力改善伤口愈合。总之，本研究表明，芒果苷通过调节高血糖诱导的巨噬细胞中 Nrf2 的活性，可能为糖尿病患者的炎症管理和促进伤口愈合提供一种有前途的治疗方法。
