C. Aurantium Peel and Seed Extracts Exhibit Neuroprotective Effect Against Glutamate–Induced Toxicity in PC12 Neuronal Cells

Neurodegenerative diseases have been associated with glutamatergic dysfunction. Recent studies have demonstrated several harmacological effects including anti-inflammatory, neuroprotective, and anticonvulsant properties of Citrus aurantium. In this study, we aimed to investigate the effects of C. aurantium peel and seed extracts against glutamateinduced oxidative damage and apoptosis. Materialsand Methods: The cultured PC12 cells were pretreated (2 hr) with varying concentrations of the extra ct (6 to 200 μg/ml), followed by exposure to glutamate (8 mM) for 24 hr. The cells viability was then measured using the MTT assay. Intracellular reactive oxygen species(ROS) and lipid peroxidation were evaluated using flurimetric assays as well as apoptosis was detected by PI staining. Results: Glutamate cytotoxicity in PC12 cells was accompanied by an increment of MDA content, ROS generation, and apoptotic induction (p < 0.01). However, pretreatment with peel and seed extracts of C. aurantium significantly increased cell viability following glutamate insults at concentrations higher than 12 μg/ml (p < 0.01). The cytoprotective potential of C. aurantium was also accompanied by decreased ROS accumulation, malondialdehyde level (p < 0.01- 0.001), and apoptotic cells following glutamate insults. The results suggest that C. aurantium protects againstglutamate-induced PC12 cells injury by decreasing oxidative stress and subsequently inhibiting apoptosis. Conclusion: C. aurantium peel and seed extracts could inhibit the glutamate-induced neurotoxicity, and these extracts have the potential to be used as a new therapeutic agent for neurodegenerative disorders. The exact mechanisms and the active compounds that are responsible for the anticonvulsive effect need to be clarified in future studies.