Neuroprotective Effects Of Citrus Flavonoids On Trauma In PC12 Cells

Reactive oxygen species (ROS) is recognized to be a critical factor in Alzheimer's disease (AD) and Parkinson's disease (PD). Compared with other organs, he brain is very sensitive to oxidative stresses and then resulted in the AD and PD. So it is a great challenge for researchers to seek and develop antioxidant substance which is low toxicity and high therapeutic effects.Citrus flavonoids, mainly existing in the pericarp of citrus fruits, has many bioactivity, such as anticancer, antioxidant, antibiosis and so on. In this study, after 95% ethanol extraction adsorb on AB-8 macroporous resin and desorption by 60% ethanol, we extracted the total citrus flavonoids from citrus peel. The yield of product was 2.61±0.23%; the total content of citrus flavonoids was 83.46±1.24% by UV method and there are mainly existing hesperidin and nobiletin in total citrus flavonoids.We investigated the protective actions of nobiletin, naringin, hesperidin, neohesperidin and total citrus flavonoids against the cytotoxicity induced by exposure to hydrogen peroxide (H2O2) (150μM,3h) in PC12 cells. The results showed that citrus flavonoids significantly (P <0.01) inhibited the decrease of cell viability (MTT reduction), prevented membrane damage (LDH release), scavenged ROS formation, reduced Caspase-3 activity, and attenuated the decrease of mitochondrial membrane potential (MMP), respectively, in H2O2-induced PC12 cells. Meanwhile, citrus flavonoids increased superoxide dismutase (SOD) and glutathione (GSH) activity, while decreased malondialdehyde (MDA), the production of lipid peroxidation, in H2O2-induced PC 12 cells. In addition, the percentage of cells undergoing H2O2-induced apoptosis was decreased in the presence of citrus flavonoids. These results first demonstrate that citrus flavonoids, even at physiological concentrations, have neuroprotective effects against H2O2-induced cytotoxicity in PC 12 cells and hesperidin has the better neuroprotective effects than other compounds. From these results, we can infer that the neuroprotective effects of flavanone glycosides were better than polymethoxylated flavones and the key antioxidation active components in the total citrus flavonoids were hesperidin and nobiletin. All the above results suggest that these dietary antioxidants are potential candidates for use in the intervention for neurodegenerative diseases.