Background: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders spread worldwide in elderly people. Methods: The Citrus peels methanolic extract (100 mg/kg body weight) was evaluated as an antiparkinsonism agent in rats through estimation of oxidative stress markers, neurotransmitter levels, energetic indices, DNA fragmentation pattern, inflammatory mediators, adenosine A2A receptor gene expression and the histopathological analysis of the brain. In addition, its effect was compared with ZM241385; an adenosine A2A receptor antagonist, as well as the classical drug; (L-dopa). Results: The methanolic extract of C. sinensis peels constituted 17.59 ± 1.92 mg GAE/g and 4.88 ± 0.43 mg CE/g of total phenolic and flavonoid content, respectively. The polyphenolic composition was qualified and quantified using HPLC/DAD and UPLC/ESI-MS analysis. HPLC/DAD analysis led to identify 8 phenolic acids and 4 flavonoids. UPLC/MS analysis led to identify 20 polyphenolic compounds, including 9 polymethoxylated flavoniods, 7 flavonoidal glycosides and 4 phenolic derivatives. Nobiletin and tangeretin were found as abundant polymethoxylated flavones while, hesperidin and 1-caffeoyl-β-D-glucose were found as abundant glycosyl flavone and phenolic derivatives, respectively. Rotenone induced rats showed a significant decrease in neurotransmitter levels, energetic and antioxidant parameters, while a significant increase in total protein, inflammatory mediators, adenosine A2A receptor gene expression, DNA and lipid peroxidation levels was recorded. Treatments with plant extract, L-dopa and ZM241385 restored these selected parameters to variable extents with a more potent effect of ZM241385 than L-dopa. Rotenone induced rats were left free without treatment; not recorded a noticeable improvement level. Conclusion: Citrus sinensis peels was rich with bioactive valuable-added products. This may lead to the development of new nutraceutical and pharmaceutical agents as well as functional food products used as anti-oxidative, anti-inflammatory and anti-parkinsonian agent.
