Anxiolytic Effects of Onion Peel Quercetin, Aloe and Doum Palm Tannins Loaded Chitosan Nanoparticles in Carboxymethyl Cellulose-Induced Oxidative Stress in Albino Mice

Background and Objective: Anxiety disorders, often linked to oxidative stress, are a major public health concern worldwide. While benzodiazepines are commonly prescribed, their use is limited by adverse effects such as sedation and dependency. This study aimed to evaluate the anxiolytic and antioxidant potential of onion peel-derived quercetin, Aloe vera extract and doum palm tannins encapsulated in chitosan nanoparticles (QATCNPs) using a carboxymethyl cellulose (CMC)-induced oxidative stress model in albino mice. Materials and Methods: QATCNPs were synthesized using the ionic gelation method and characterized by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and dynamic light scattering (DLS), revealing a mean particle size of 150.32 nm. Thirty albino mice were divided into five groups (n = 6): Control, CMC-only, diazepam (2 mg/kg), chitosan NPs (50 mg/kg) and QATCNPs (50 mg/kg). Behavioral tests, including the elevated plus maze (EPM) and open field test (OFT), assessed anxiolytic behavior. Biochemical assays quantified oxidative stress markers: malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH). Physiological and neurochemical markers were also measured. Data are presented as Mean±SE and statistical differences among groups were analyzed using One-Way ANOVA followed by Tukey’s post-hoc test (p<0.05). Results: The QATCNP-treated group spent significantly more time in the open arms of the EPM (150.00±5.00 sec) and center of the OFT (170.00±5.00 sec) compared to the CMC-only group (50.00±3.00 and 40.00±3.00 sec, respectively). The MDA levels decreased to 2.10±0.10 nmol/mg protein in the QATCNP group compared to 4.50±0.12 nmol/mg in the CMC group. Antioxidant enzyme levels increased significantly: CAT (32.00±1.20 U/mg), SOD (18.00±0.80 U/mg) and GSH (8.20±0.50 μmol/mg) in QATCNP-treated mice. Furthermore, GABA, serotonin and neuropeptide Y levels were significantly elevated in the QATCNP group, indicating neurochemical modulation. Conclusion: QATCNPs significantly reduced anxiety-like behavior and oxidative stress while enhancing neuroprotective markers, suggesting their potential as a safe and effective therapeutic strategy for anxiety management.