Carica papaya leaf extract-loaded chitosan/polyethylene glycol/nickel oxide nanocomposites shows neuroprotective effects against streptozotocin-induced diabetic neuropathy in rats via down-regulating MAPK pathway

Diabetic neuropathy represents a devastating microvascular complication of diabetes mellitus, characterized by progressive nerve damage arising from chronic hyperglycemia and associated metabolic derangements. Current therapeutic strategies for diabetic neuropathy are often insufficient, highlighting an urgent need for more effective interventions to inhibit the disease progression. The present study focused on the synthesis and characterization of C. papaya leaf extract-loaded chitosan-polyethylene glycol-nickel oxide nanocomposites (CP-Ch/PEG/NiO NCs) and the assessment of their therapeutic efficacy against streptozotocin (STZ)-induced diabetic neuropathy in rats. The CP-Ch/PEG/NiO NCs was synthesized by using the chemical precipitation technique, and they were subsequently characterized using different techniques, including UV-visible spectroscopy, X-ray diffractometer (XRD), scanning electron microscope (SEM) equipped with energy-dispersive X-ray (EDAX), Fourier transform infrared (FT-IR), photoluminescence (PL), and dynamic light scattering (DLS) methods. The therapeutic effects of synthesized CP-Ch/PEG/NiO NCs against diabetic neuropathy were assessed using STZ-induced rats. The blood glucose, body weight, and insulin were evaluated in the experimental rats. The locomotor and exploratory behaviors of the experimental rats were assessed using the open field test (OFT). The concentrations of insulin‐like growth factor (IGF), nerve growth factor (NGF), inflammatory cytokines, and mitogen-activated protein kinase (MAPK) pathway proteins were evaluated in the sciatic nerves of the experimental rats. The brain hippocampus tissues were subjected to the histopathological analysis. The findings of several characterization techniques indicated the formation of crystalline CP-Ch/PEG/NiO NCs with spherical structures, with an average particle size of 77.50 nm. The treatment with synthesized CP-Ch/PEG/NiO NCs considerably reduced the blood glucose, and elevated the insulin and body weight in the STZ-induced rats. Furthermore, the CP-Ch/PEG/NiO NCs enhanced the locomotor and exploratory behaviors and walking ability of the STZ-induced rats. The treatment with CP-Ch/PEG/NiO NCs elevated the IGF and NGF levels, decreased the inflammatory cytokine levels, and markedly down-regulated the MAPK pathway in the sciatic nerves of STZ-induced rats with diabetic neuropathy. Moreover, the results of histopathological analysis of hippocampus tissues suggested the neuroprotective effects of the CP-Ch/PEG/NiO NCs against diabetic neuropathy in rats. The key results of this study suggest that the synthesized CP-Ch/PEG/NiO NCs have advantageous effects in alleviating diabetic neuropathy in STZ-induced rats. The present findings indicate that the CP-Ch/PEG/NiO NCs may serve as a feasible therapeutic alternative for diabetic neuropathy treatment.