Natural polyphenols are widely reported to have a large range of pharmacological properties, especially antioxidant activities and free radical scavenging capacities. In this study, we investigate the effects of naringin, chlorogenic acid, and quercetin mixtures (NCQ) on renal fibrosis in streptozotocin (STZ)-induced diabetic aged rats and its underlying mechanisms for ten consecutive weeks. The oxidative defense system in the kidneys of treated rats was found to be improved. Several biomarkers were investigated including the blood urea nitrogen, creatinine, and uric acid. Moreover, antioxidant parameters were evaluated and we found that superoxide dismutase, catalase, glutathione peroxidase, Na⁺-K⁺-ATPase activities, the nitric oxide production, the protein carbonyl, the advanced oxidation protein products, lipid peroxidation, and reduced glutathione levels were all significantly balanced and close to control values. In addition, NCQ restored renal injuries and fibrosis as assessed by histological method and molecular biology investigation of the matrix metalloproteinase, the transforming growth factor-beta TGF-β, the tumor necrosis factor TNFα, and p53 expression. Our study proposes the NCQ combination as potential plant-derived bioactive compounds to prevent diabetic nephropathy.

Nanomaterials have gained considerable attention for diverse medical applications, particularly in neurology. Copper oxide nanoparticles (CuO-NPs) exhibit unique nanoscale properties that enable close interactions with neuronal cells, highlighting their potential as therapeutic agents for modulating synaptic plasticity and improving cognitive function. We aimed to investigate whether low-dose CuO-NPs can enhance fear extinction memory and increase intrinsic excitability in the infralimbic cortex (IL) of male mice. Adult male mice were subjected to fear conditioning using auditory cues paired with footshocks. Following the administration of a low dose of CuO-NPs, behavioral performance was assessed by measuring freezing responses during extinction. Whole-cell patch-clamp recordings were then performed on IL pyramidal neurons to evaluate intrinsic excitability and AMPA/NMDA ratio. Transmission electron microscopy (TEM) was applied after 2 and 24 h to assess the ability of CuO-NPs to reach the brain. We demonstrated via TEM that CuO-NPs efficiently cross the blood-brain barrier within 24 h' post-administration. Using cued fear conditioning, we subsequently found that a single intraperitoneal injection of CuO-NPs enhanced fear extinction memory, as evidenced by a significant reduction in freezing behavior compared to control animals. Patch-clamp analysis confirmed that CuO-NPs increased the excitability of IL pyramidal neurons and induced a sustained reduction in fast, medium, and slow post-spike after hyperpolarizations. Additionally, we demonstrated that CuO-NPs increased N-methyl-d-aspartate receptor-mediated synaptic currents, suggesting an enhanced synaptic plasticity in the infralimbic cortex. Our findings offer new insights into the potential use of CuO-NPs for modulating fear extinction memory.