Ameliorating effect of Citrus trifoliata L. fruits extract on motor incoordination, neurodegeneration and oxidative stress in Parkinson’s disease model

ABSTRACT

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
• UPLC-HRMS
• manganese animal models
• neuroprotective effect
• Parkinsonism
• neurotransmitters
• oxidative stress
• striatum

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data are available upon reasonable request from the corresponding author.

Additional information

Notes on contributors

Mostafa A. Abdel-Kawy

Mostafa A. Abdel-Kawy: Mostafa Aly Abdelkawy is working as Emirate Professor Doctor of Pharmacognosy at the Pharmacognosy Department, Faculty of Pharmacy Cairo University with fifty-two years’ experience making research, beside teaching for both graduate and undergraduate levels, not only for Pharmacy students’ Cairo University but also students’ belonging to the KSA and Libyain Universities and medical sector in Egypt, supervising and helping students to make research at the postgraduate level.

Basma Emad Aboulhoda

Basma Emad Aboulhoda: is working as Associate Professor of Anatomy and Embryology, Faculty of medicine, Cairo University with thirteen years’ experience making research and supervising thesis beside teaching both graduate and undergraduate medical students with more than 50 research paper in the field of histology, cell biology, virology, pharmacology and biology.

Camilia G. Michel

Camilia G. Michel is working as Emirate Professor Doctor of Pharmacognosy at the Pharmacognosy Department, Faculty of Pharmacy Cairo University with forty-one years’ experience making research, beside teaching for both graduate and undergraduate levels, not only for Pharmacy students’ but also students’ belonging to the medical sector in Egypt, supervising and helping her students to make research at the postgraduate level. A believer in the power of quality management to accelerate progress in healthcare, Camilia is working at the National Authority for Quality Assurance and Accreditation (NAQAAE) in Egypt since 2018, with expertise and purpose, to solve the Egyptian’s toughest educational challenges regarding the medical sector.

Mohamed S. Sedeek

Mohamed S. Sedeek is a lecturer at the Department of Pharmacognosy, Faculty of Pharmacy, Cairo University. Mohamed focused on development of different strategies for valorization of citrus peels during his MSc. and PhD work and provided a nano-based valorization approach for the residual peels generated as byproduct of citrus fruits processing, allowing for enhancement of the efficiency of natural fungicides and pesticides. He got the prize of the best Msc thesis in Pharmaceutical Sciences of Professor Dr. Abd El- Azim Hifny Saber at 2016 and the prize of the best PhD thesis in Pharmaceutical Sciences at 2021 from Faculty of Pharmacy, Cairo University. Mohamed has a very good experience in plant metabolomics and natural products chemistry, based on UPLC-MS/MS, GC/MS and, other chromatographic techniques. Currently, Mohamed is focusing on metabolomic analysis of functional food and investigation of their biological activities, as well as, discovery of natural lead compounds.

Farid N. Kirollos

Farid N. Kirollos (PH.D) is working as associate professor of pharmacognosy at the pharmacognosy department, Faculty of Pharmacy, Cairo University with more than 33 years experience in teaching pharmacognosy, phytochemistry and phytotherapy to the undergraduate students not only in Cairo University but also in many other universities in and outside Egypt. Farid also has a great experience in teaching postgraduate students. Moreover, Farid is interested in research and has many international publications.

Marwa A. Masoud

Marwa A. Masoud: Works at National Organization for Drug Control & Research | NODCAR · Department of Pharmacology.