"Taxifolin modulates diabetic neuropathy and inhibits insulin fibrillation: A dual mechanistic insight"

Diabetic neuropathy (DN), a pathological condition impacting peripheral nerves, is caused by the demyelination of nerve fibers due to damage to the protective myelin sheath. Leveraging the known therapeutic potential of phytochemicals from medicinal plants, particularly in neurodegenerative disorders, this research aimed to evaluate taxifolin's role as an anti-amyloidogenic agent on human insulin amyloid formation and its efficacy in alleviating diabetic peripheral neuropathy (DPN) in male Wistar rats. The anti-fibrillatory effect of taxifolin, even at very low concentrations, on human insulin fibrillation was comprehensively demonstrated using various biophysical techniques, including light scattering assay, Thioflavin T assay, far-UV Circular Dichroism spectroscopy, and Transmission Electron Microscopy. Additionally, taxifolin was shown to destabilize preformed human insulin fibrils in a concentration-dependent manner. In the in-vivo component, taxifolin-treated rats exhibited a significant divergence in behavioral parameters associated with neuropathy, such as hyperalgesia and allodynia, when compared to streptozotocin-diabetic controls. Recognizing the involvement of oxidative stress in neuronal cell damage, taxifolin was found to reduce the generation of reactive oxygen species (ROS) and suppress pro-inflammatory cytokines, specifically tumor necrosis factor-alpha (TNF-α) and nerve growth factor (NGF). Furthermore, structural alterations were observed in rat brains and sciatic nerves through histopathological and transmission electron microscopic (TEM) analyses, underscoring taxifolin's multifaceted neuroprotective effects.