Comparative Evaluation of Quercetin, Pioglitazone, Insulin, and Novel 5-Chromenyl–Methylene Thiazolidinedione Derivative on Nerve Function in Experimental Diabetic Peripheral Neuropathy

<b>Background:</b> A debilitating complication of diabetes is diabetic peripheral neuropathy (DPN), for which effective therapy remains limited. In this research, we evaluated the effects of quercetin, pioglitazone, insulin, and a novel thiazolidine-2,4-dione derivative (TZDd) on the nerve functions in a streptozotocin (STZ)-induced rat model of DPN. <b>Methods:</b> In the experimental groups, STZ (60 mg/kg) was administered to Wistar rats to induce type 1 diabetic neuropathy, and the control and experimental DPN groups were treated with quercetin, pioglitazone, insulin, or TZDd for 5 weeks. The sensory and motor symptoms of DPN were evaluated via behavioral tests, nerve conduction velocity measurements, and electrophysiological assessment, and the synthesized TZDd was evaluated in silico for its pharmacokinetic, toxicological, and drug-likeness properties. <b>Results:</b> The diabetic rats developed DPN after 2 weeks of STZ administration, as evidenced by the significant reduction in the sensory and motor nerve conduction velocities (SNCVs and MNCVs) and increased mechanical hyperalgesia; on the other hand, quercetin, pioglitazone, insulin, and TZDd administration ameliorated the nerve functions of the DPN rats. In the in silico predictions, the novel TZDd exhibited no toxicity risks and demonstrated drug-like properties. <b>Conclusions:</b> Quercetin, pioglitazone, insulin, and TZDd showed neuroprotective effects that enhanced functional recovery in experimental DPN. These findings highlight that TZDd may represent a valuable compound with neuroprotective effects that could be used in DPN therapy and management.