Khanna Saumya, Kumar Sachindra, Sharma Pratyasha, Daksh Rajni, Nandakumar Krishnadas, Shenoy Rekha Raghuveer
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104.
Inflammopharmacology. 2025 Apr 9. doi: 10.1007/s10787-025-01729-7.
A common and serious side effect of diabetes is diabetic peripheral neuropathy (DPN), which is characterised by gradual nerve damage brought on by oxidative stress, chronic inflammation, and prolonged hyperglycemia. Studies identify NLRP3 inflammasome as a key mediator in the pathogenesis of DPN, connecting neuroinflammation and neuronal damage to metabolic failure. Because of their strong anti-inflammatory and antioxidant qualities, flavonoids, a broad class of naturally occurring polyphenols, have drawn interest as potential treatments for DPN. The various ways that flavonoids affect the NLRP3 inflammasome and their potential as a treatment for DPN are examined in this review. It has been demonstrated that flavonoids prevent NLRP3 activation, which lowers the release of pro-inflammatory cytokines including IL-1β and IL-18 and causes neuroinflammation. Flavonoids work mechanistically by reducing oxidative stress, altering important signalling pathways, and blocking the activities of NF-κB and caspase-1, which are both essential for the activation of the NLRP3 inflammasome. Preclinical research has shown that flavonoids have strong neuroprotective benefits, and few clinical evidence also points to the potential of flavonoids to improve nerve function and lessen neuropathic pain in diabetic patients. The current review emphasises how flavonoids may be used as a treatment strategy to target inflammation in DPN caused by the NLRP3 inflammasome. By targeting important inflammatory pathways, flavonoids provide a new way to slow the progression of this debilitating illness. Further investigation into the mechanisms, clinical translation, and novel drug delivery techniques could enhance the therapeutic efficacy of diabetic peripheral neuropathy.
糖尿病常见且严重的副作用是糖尿病性周围神经病变（DPN），其特征是由氧化应激、慢性炎症和长期高血糖引发的渐进性神经损伤。研究确定NLRP3炎性小体是DPN发病机制中的关键介质，将神经炎症和神经元损伤与代谢功能衰竭联系起来。黄酮类化合物是一类广泛存在的天然多酚，因其强大的抗炎和抗氧化特性，作为DPN的潜在治疗方法而受到关注。本综述探讨了黄酮类化合物影响NLRP3炎性小体的各种方式及其作为DPN治疗方法的潜力。已证明黄酮类化合物可阻止NLRP3激活，从而降低促炎细胞因子如IL-1β和IL-18的释放并引发神经炎症。黄酮类化合物的作用机制是通过减少氧化应激、改变重要信号通路以及阻断对NLRP3炎性小体激活至关重要的NF-κB和caspase-1的活性。临床前研究表明黄酮类化合物具有强大的神经保护作用，少量临床证据也表明黄酮类化合物有改善糖尿病患者神经功能和减轻神经性疼痛的潜力。当前综述强调了黄酮类化合物如何作为一种治疗策略来靶向由NLRP3炎性小体引起的DPN中的炎症。通过靶向重要的炎症途径，黄酮类化合物为减缓这种使人衰弱疾病的进展提供了一种新方法。对其机制、临床转化和新型药物递送技术的进一步研究可能会提高糖尿病性周围神经病变的治疗效果。
