Plant-Derived Bioactives and Nanotechnology-Enabled Delivery in Diabetic Neuropathy: Molecular Mechanisms, Therapeutic Advances, and Translational Perspectives.

Diabetic neuropathy (DN), a long-term and progressive complication of diabetes mellitus, impairs approximated half of patients with diabetes and affects the quality of life considerably because of pain, sensory deficiency, and motor deficits. Traditional treatment including anticonvulsants, antidepressants, and opioids derived agentshas provided some non-specific symptomatic benefit without aiming at the underlying causes like oxidative stress, chronic inflammation, and mitochondrial dysfunction. Curcumin, resveratrol, quercetin, and ginsenosides are few of phytochemicals, that are multi-targeted and can be used as therapeutic agents in DN treatment due to their antioxidant, anti-inflammatory, neuroprotective, and anti-glycation properties. These molecules have the effect of modulating redox-sensitive pathways, like NF-KB, SIRT1 and Nrf2, improving mitochondrial activity, inhibiting pro-inflammatory cytokines (TNF-alpha, IL-6), and stimulating nerve regeneration through neurotrophic factors such as NGF and BDNF. Although they have a promising pharmacological profile, problems like low oral bioavailability, non-clinical standardization, and regulatory concerns hinder their adoption to clinical applications. The review also addresses the importance of large-scale and randomized clinical trials to confirm efficacy and develop uniform dosing regimens.