Protective effect of coumarin on diabetes-induced sciatic nerve damage in rats via TRPV1 modulation.

Diabetes-induced peripheral nerve damage is a major complication of chronic hyperglycemia, characterised by oxidative stress, inflammation, and apoptosis. The transient receptor potential vanilloid 1 (TRPV1) channel has been identified as a key regulator linking these pathological processes. In this study, the neuroprotective effects of coumarin (CMR) on diabetic-induced sciatic nerve damage and its potential regulatory role on TRPV1 signalling pathways were investigated. Experimental diabetes was induced in Wistar rats by administering streptozotocin (45 mg/kg, i.p.), and the animals were given CMR (100 mg/kg/day, i.g.) for 14 days, beginning immediately after confirmation of diabetes (72 h post-STZ administration). Oxidative stress markers (GSH, MDA, SOD, CAT, NO), inflammatory cytokines (IL-1β, IL-6, TNF-α) and the transcription factor NF-κB, apoptotic markers (caspase-3, caspase-9, PARP-1), BDNF levels, and TRPV1 expression were evaluated in sciatic nerve tissues using biochemical, Western blot, and immunohistochemical methods. In the diabetic group, oxidative stress, inflammation, apoptosis, and TRPV1 expression were significantly increased, while antioxidant capacity and BDNF levels were decreased (p < 0.05). CMR treatment significantly reversed these changes, restoring redox balance, suppressing pro-inflammatory and apoptotic pathways, and increasing BDNF levels (p < 0.05). Furthermore, the diabetes-induced upregulation of TRPV1 was significantly attenuated. Histopathological findings showed structural improvement in sciatic nerve tissue and decreased glial activation. In conclusion, CMR exerts a significant neuroprotective effect against diabetes-induced sciatic nerve damage by modulating TRPV1-associated oxidative, inflammatory, and apoptotic pathways, highlighting its potential as a targeted therapeutic candidate.