Antidepressant and memory-improving effects of zinc oxide-catechin nanocomposites following d-galactose administration in rats.

Excessive dietary sugar such as D-galactose (Dgalc) is associated with metabolic and neurological disturbances and induces oxidative stress and neuroinflammatory cascades that provoke depressive-like behavior and memory deficits. Catechin (Catn), a phytochemical compound, has been documented to possess diverse pharmacological properties. To enhance its therapeutic properties, Catn was articulated as ZnO-functionalized nanoparticles (ZnO-CatnNPs), which maintain stability, bioavailability, and cellular uptake, presenting a promising nanotechnology-based approach to treat Dgalc-induced neurobehavioral and biochemical alterations. In the present study, after physical characterization (UV, FTIR, XRD, EDX, and SEM), ZnO-CatechNps were evaluated for their behavioral, biochemical, neurochemical, and histopathological effects in a D-galactose-induced model of memory impairment and depressive-like behavior in rats. The 48 animals were divided among eight groups (n = 6 each): Vh + Vh (1 ml/kg), Vh + Catn (50 mg/ml/kg), Vh + ZnONps (10 mg/ml/kg), Vh + ZnO-CatnNps (10 mg/ml/kg), Vh + Dgalc (300 mg/ml/kg), Dgalc + Catn, Dgalc + ZnONps, and Dgalc + ZnO-CatnNps (10 mg/ml/kg). Treatments were administered intraperitoneally (i.p) once daily for 28 days. The Forced Swim Test (FST) on day 29 and Morris Water Maze (MWM) on day 30th and 31st were used to assess depressive-like behavior and memory performance, respectively. After behavioral testing, on day 32, animals were decapitated, and whole brain tissue was collected for biochemical, neurochemical, and histopathological analysis. The findings demonstrated that Dgalc administration markedly suppressed antioxidant enzyme activity, enhanced oxidative stress indices, elevated pro-inflammatory cytokines, disrupted serotonergic AChE function, and altered 5-HT1A receptor responsiveness, inducing histopathological damage in brain tissue. Conversely, administration of Catn, ZnONPs, and ZnO-CatnNPs mitigated the negative effects of Dgalc as reflected via decreased depressive-like behavior, improved memory function, antioxidant defense status, and preserved the brain morphology. The results underscore the potential impact of ZnO-CatnNPs under Dgalc exposure on behavioral, biochemical, and neurochemical changes, supporting their protective impacts as a therapeutic agent for depressive-like behavior and memory-related neurological deficits via their antioxidant, anti-inflammatory, and neuromodulatory mechanisms. On the contrary, administration of Catn, ZnONPs, and ZnO-CatnNPs mitigated the negative effects of Dgalc as reflected via decreased depression-like behavior, improved memory function, antioxidant defense status, and preserved the brain morphology. The results underscore the potential impact of ZnO-CatnNps under Dgalc exposure on behavioral, biochemical, and neurochemical changes, supporting their protective impacts as a therapeutic agent for depressive-like behavior and memory-related neurological deficits via their antioxidant, anti-inflammatory, and neuromodulatory mechanisms. The observed efficacy can be attributed to elevated bioavailability, persistent release, and greater cellular association of Catn mediated by ZnO-based nano-formulation.