Neuroprotective Activity of Eriodictyol Against Streptozotocin-Induced Diabetic Peripheral Neuropathy in Wistar Rats by Targeting Wnt/β-Catenin Pathway.

Long-term hyperglycemia and insulin dysfunction deteriorate peripheral nerve functions, leading to sensory loss, spontaneous pain, and hypersensitivity (i.e., allodynia and hyperalgesia). Evidence indicates glucose-induced upregulation of the Wnt/β-catenin mechanism in diabetic peripheral neuropathy (DPN). Eriodictyol (Ed) has shown protective effects against glucotoxicity. The present study explored the bioactivity of Ed in streptozotocin (STZ) induced DPN and the role of the Wnt/β-catenin pathway. Ed or gabapentin (Gpn), or methyl vanillate (MV) was administered in Wistar rats for 4 weeks, starting 6 weeks after STZ administration. Ed ameliorated the mean body weight and mitigated polydipsia and polyphagia in DPN rats. The data indicated that Ed attenuated hyperglycemia, glycosylated hemoglobin (HbA1c) levels, and HOMA-IR, and enhanced circulating insulin levels and HOMA-β against STZ-induced DPN. MV (Wnt/β-catenin activator) caused a significant increase in STZ-induced hyperglycemia, HbA1c, HOMA-IR, and further decreased the insulin levels and HOMA-β in STZ-treated rats. Ed attenuated oxidative stress, inflammatory expression, level of advanced glycation end products, and nuclear factor kappa B in the sciatic nerve of STZ-treated neuropathic rats, and MV further potentiated these markers triggered by STZ. Interestingly, Ed and Gpn attenuated mRNA expression of Wnt1/β-catenin in the sciatic nerve of neuropathic rats. Hyperalgesia and allodynia were significantly ameliorated in Ed or Gpn-treated rats against DPN. Furthermore, Ed ameliorated the biochemical biomarkers, histopathological characteristics, and nociceptive-like responses in STZ and MV-treated rats. It is concluded that Ed can alleviate the pathogenic course of DPN. Wnt/β-catenin pathway might be involved in the eriodyctiol-triggered mitigation of nociceptive-like responses in diabetic rats.