Therapeutic potential of Citrus sinensis peels against rotenone induced Parkinsonism in rats

Background: Parkinson's disease (PD) is one of the most common neurodegenerative disorders spread worldwide in elderly people. Methods: The Citrus peel methanolic extract (100 mg/kg body weight) was evaluated as anti-parkinsonism 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; adenosine A2A receptor antagonist as well as the classical drug; levodopa. 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-βD-glucose were found as abundant glycosyl flavone and phenolic derivatives, respectively. Rotenone induced rats showed significant decrease in neurotransmitter levels, energetic and antioxidant parameters, while significant increase in total protein, inflammatory mediators, adenosine A2A receptor gene expression, DNA and lipid peroxidation levels were recorded. Treatments with plant extract, L-dopa and ZM241385 restored these selected parameters to variable extents with more potent effect of ZM241385 than L-dopa. Rotenone induced rats left free without treatment not recorded a noticeable improvement level. Conclusion: Citrus sinensis peel 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.