The protective effects of Citrus aurantium flower extract against 6-hydroxydopamine-mediated cell damage in human neuroblastoma SH-SY5Y cells / Los efectos protectores del extracto de flor de Citrus aurantium contra el daño celular mediado por 6-hidroxidopamina en células humanas de neuroblastoma SH-SY5Y

Parkinson's disease (PD) is described as a neurological condition, resulting from continuous degeneration of dopaminergic neurons. Currently, most treatments for neurodegenerative diseases are palliative. In traditional Iranian medicine, Citrus aurantium flower extract is used to treat some neural diseases, such as sleep disorders and anxiety. The tendency towards the use of medicinal herbs for the treatment of diseases (eg, seizure) is growing. Accordingly, we evaluated the antioxidant effects of C. aurantium flowers and analyzed their protective effects against 6-hydroxydopamine (6-OHDA)-mediated oxidative stress. In this study, 150 mM of 6-OHDA was used to induce cellular damage. Also, MTT assay was performed to analyze cellular viability. Fluorescence spectrophotometry was performed to measure the intracellular reactive oxygen species (ROS) and calcium levels. Based on the findings, 6-OHDA could reduce cell viability. We also analyzed the effects of C. aurantium against neurotoxicity. The intracellular levels of ROS and calcium greatly improved in cells exposed to 6-OHDA. SH-SY5Y cell incubation with C. aurantium (400 and 600 mg/mL) induced protective effects and decreased the biochemical markers of cell apoptosis. According to the findings, C. aurantium showed protective effects against neurotoxicity, caused by 6-OHDA; these protective properties were accompanied by antiapoptotic features. According to the findings, it seems that hydromethanolic C. aurantium extract can be used to prevent seizures.

La enfermedad de Parkinson (EP) se describe como una afección neurológica que resulta de la degeneración continua de las neuronas dopaminérgicas. Actualmente, la mayoría de los tratamientos para las enfermedades neurodegenerativas son paliativos. En la medicina tradicional iraní, el extracto de flor de Citrus aurantium se usa para tratar algunas enfermedades neurológicas, como los trastornos del sueño y la ansiedad. La tendencia hacia el uso de las medicinas para el tratamiento de enfermedades (por ejemplo, convulsiones) está creciendo. Por consiguiente, el objetivo de este trabajo consistió en evaluar los efectos antioxidantes de las flores de C. aurantium y analizar sus efectos protectores contra el estrés oxidativo mediado por la 6- hidroxidopamina (6-OHDA). En este estudio, se usó 150 mM de 6-OHDA para inducir daño celular. Además, se realizó un ensayo de MTT para analizar la viabilidad celular. La espectrofotometría de fluorescencia se realizó para medir las especies reactivas de oxígeno (ROS) intracelulares y los niveles de calcio. En base a los hallazgos, 6-OHDA podría reducir la viabilidad celular. También analizamos los efectos de C. aurantium contra la neurotoxicidad. Los niveles intracelulares de ROS y calcio se expandieron a las células expuestas a 6-OHDA. La incubación de células SH-SY5Y con C. aurantium (400 y 600 mg / ml) indujo efectos protectores y disminuyó los marcadores bioquímicos de la apoptosis celular. De acuerdo con los hallazgos, C. aurantium mostró efectos protectores contra la neurotoxicidad, causada por 6-OHDA; estas propiedades protectoras fueron acompañadas por características antiapoptóticas. Según los hallazgos, parece que el extracto hidrometanólico de C. aurantium se puede usar para prevenir las convulsiones.

Brain Region Specificity of Mitochondrial Biogenesis and Bioenergetics Response to Nrf2 Knockdown: A Comparison Among Hippocampus, Prefrontal Cortex and Amygdala of Male Rat Brain

ABSTRACT Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been identified as the well-known coordinator of intracellular antioxidant defense system. Herein, we aimed to evaluate the effects of Nrf2 silencing on mitochondrial biogenesis markers peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor-1(NRF-1), mitochondrial transcription factor A (TFAM) and cytochrome c as well activities of two enzymes citrate synthase (CS) and malate dehydrogenase (MDH) in three brain regions hippocampus, amygdala, and prefrontal cortex of male Wistar rats. Small interfering RNA (siRNA) targeting Nrf2 was injected in dorsal third ventricle. Next, western blot analysis and biochemical assays were used to evaluation of protein level of mitochondrial biogenesis factors and CS and MDH enzymes activity, respectively. Based on findings, whilst Nrf2-silencing led to notably reduction in protein level of mitochondrial biogenesis upstream PGC-1α in three brain regions compared to the control rats, the level of NRF-1, TFAM and cytochrome c remained unchanged. Furthermore, although Nrf2 silencing increased CS activity, activity of MDH significantly decreased in hippocampus and prefrontal cortex areas. Interestingly, CS and MDH activities in amygdala did not change after Nrf2 knockdown. In conclusion, the present findings highlighted complexity of interaction of Nrf2 and mitochondrial functions in a brain region-specific manner. However, by outlining the exact interaction between Nrf2 and mitochondria, it would be possible to find a new therapeutic strategies for neurological disorders related to oxidative stress.