A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes

Abstract

Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD.

Bioactive Compounds of Citrus Fruits: A Review of Composition and Health Benefits of Carotenoids, Flavonoids, Limonoids, and Terpenes

“…The antioxidant activity of citrus bioactive compounds, especially flavonoids, carotenoids, terpenes, and limonoids, can attenuate oxidative stress-related disorders [ 80 , 81 ]; they thus have potential applications against obesity [ 82 ], inflammatory diseases [ 32 , 83 , 84 ], atherosclerosis [ 85 ], neurodegenerative diseases [ 86 , 87 , 88 ], and cancer [ 89 , 90 ] ( Table 3 ).…”

The Second Life of Citrus Fruit Waste: A Valuable Source of Bioactive Compounds

“…Moreover, mandarin peel, as well as lemon and grapefruit ones, showed immunomodulatory activity, since it increased the proliferation of mouse splenocytes and antigenotoxic effect, through reduction of cisplatin-induced chromosomal aberrations in the same experimental model [ 81 ]. Interestingly, a flavonoid-rich extract of C. reticulata juice showed promising anti-cancer activity in anaplastic thyroid carcinoma cell lines [ 82 ], as well as proved to be a strong neuroprotective agent in an in vitro model of Parkinson’s disease [ 83 ].…”

Prunus cerasoides Extract and Its Component Compounds Upregulate Neuronal Neuroglobin Levels, Mediate Antioxidant Effects, and Ameliorate Functional Losses in the Mouse Model of Cerebral Ischemia

“…Some experimental studies have reported that flavonoid-rich extracts exhibit antioxidant properties by inhibiting free radical production in oxidative stress-induced cells [ 48 ] and mitigating I/R-induced brain damage in rats [ 49 ]. It has also been shown that isoflavonoid-rich extracts exhibit potent antioxidant activity by scavenging ROS [ 50 ].…”