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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.1
- 수록면
- 73 - 86 (14page)
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Nobiletin, a polymethoxylated flavonoid found in citrus, has been studied because of its modulatory functions in cellular signaling cascades, and effects to prevent mitochondrial calcium overload and neuronal cell death. Particularly, we previously reported that nobiletin induced changes in the mitochondrial membrane potential through K+ channel regulation, suggesting that nobiletin might exert neuroprotective effects via regulating mitochondrial functions associated with the electron transport chain (ETC) system. This study investigated whether nobiletin regulated mitochondrial dysfunction mediated by ETC system downregulation by inhibiting complex I (CI) and complex III (CIII) in pure mitochondria and the cortical neurons of rats. The results showed that nobiletin significantly reduced mitochondrial reactive oxygen species (ROS) production, inhibited apoptotic signaling, enhanced ATP production and then restored neuronal viability under conditions of CI inhibition, but not CIII inhibition. These effects were attributed to the downregulation of translocation of apoptosis-induced factor (AIF), and the upregulation of CI activity and the expression of antioxidant enzymes such as Nrf2 and HO-1. Together with our previous study, these results indicate that the neuroprotective effects of nobiletin under mitochondrial dysfunction may be associated with its function to activate antioxidant signaling cascades. Our findings suggest the possibility that nobiletin has therapeutic potential in treating oxidative neurological and neurodegenerative diseases mediated by mitochondrial dysfunction.
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참고문헌 (58)
참고문헌 신청
Huang H / 2016 / The multifunctional effects of nobiletin and its metabolites in vivo and in vitro / Evid Based Complement Alternat Med 2016:2918796
Onozuka H / 2008 / Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer's disease / J Pharmacol Exp Ther 326:739~744
Yabuki Y / 2014 / Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice / Neuroscience 259:126~141
Yamamoto Y / 2009 / Nobiletin improves brain ischemiainduced learning and memory deficits through stimulation of CaMKII and CREB phosphorylation / Brain Res 1295:218~229
이지형 / 2018 / Nobiletin attenuates neurotoxic mitochondrial calcium overload through K+ influx and ΔΨm across mitochondrial inner membrane / The Korean Journal of Physiology & Pharmacology 22(3):311~319
Onozuka H / 2008 / Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimer's disease / J Pharmacol Exp Ther 326:739~744
Yabuki Y / 2014 / Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice / Neuroscience 259:126~141
Yamamoto Y / 2009 / Nobiletin improves brain ischemiainduced learning and memory deficits through stimulation of CaMKII and CREB phosphorylation / Brain Res 1295:218~229
이지형 / 2018 / Nobiletin attenuates neurotoxic mitochondrial calcium overload through K+ influx and ΔΨm across mitochondrial inner membrane / The Korean Journal of Physiology & Pharmacology 22(3):311~319
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