Background: Citrus trifoliate fruit (also known as Trifoliate orange) is one of the commercially-cultivated Citrus genus of plants belonging to the Rutaceae family. It has been traditionally-utilized in treatment of neurodegenerative disorders. However, the scientific evidence verifying this utilization needs further elucidation.
Aim of the study: Characterization of the bioactive constituents of C. trifoliata L. fruits extract and evaluating its effect on Parkinson's disease (PD) model.
Material and methods: Rats were classified into 5 groups; control, PD, PD-treated by L-dopa/Carpidopa and PD-treated by oral Citrus trifoliata L. fruits extract (50 and 100 mg/kg). Deterioration in brain functions was evaluated through an in vivo open field, grid and catalepsy tests. The study also assessed the striatal neurotransmitters, oxidative stress markers and histopathological changes.
Results: Citrus trifoliata L. fruit extract has revealed motor improvement comparable to L-dopa and carbidopa. It has also effectively-improved oxidative stress via reduction of striatal malondialdehyde & nitric oxide along with replenishment of the striatal glutathione and superoxide dismutase. The extract caused significant reduction of the striatal myeloperoxidase activity and restoration of dopamine, γ-amino butyric acid (GABA), and acetylcholinesterase. This effect was further confirmed by amelioration of neuronal apoptosis, microgliosis and peri-neuronal vacuolation. Metabolite profiling revealed 40 constituents, with flavonoids representing the main identified class.
Conclusion: The neuro-protective effect of Citrus trifoliata extract was achieved through the antioxidant and anti-inflammatory activities of its flavonoids, particularly hesperidin and naringin. This neuro-protective effect was evident at the behavioral, histological and neurotransmitter levels.
Keywords: Citrus trifoliata L; Parkinsonism; UPLC-HRMS; manganese animal models; neuroprotective effect; neurotransmitters; oxidative stress; striatum.