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Flavonoids regulating NLRP3 inflammasome: a promising approach in alleviating diabetic peripheral neuropathy

Saumya Khanna,Sachindra Kumar,Pratyasha Sharma,Rajni Daksh,K. Nandakumar,R. Shenoy

Published 2025 in InflammoPharmacology

ABSTRACT

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. Flavonoid intervention in Diabetic Neuropathy and its role in NLRP3 Inflammasome Flavonoid intervention in Diabetic Neuropathy and its role in NLRP3 Inflammasome

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