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Year : 2015  |  Volume : 11  |  Issue : 44  |  Page : 284-289

Neuroprotective effect of Citrus unshiu immature peel and nobiletin inhibiting hydrogen peroxide-induced oxidative stress in HT22 murine hippocampal neuronal cells

1 Research and Development Team, Jeonnam Development Institute of Korean Traditional Medicine, 288 Udeuraendeu-gil, Anyang-myun Jangheung-gun, Jeonnam 529-851, Korea
2 Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, 20, Geonjiro, Deokjin-gu, Jeonju 561-712, Korea

Correspondence Address:
In Young Choi
Jeonnam Development Institute of Korean Traditional Medicine, 288 Udeuraendeu-gil, Anyang-myun Jangheung-gun, Jeonnam 529-851
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1296.166047

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Background: Oxidative stress-induced cell damage is common in the etiology of several neurobiological disorders, including Alzheimer's disease and Parkinson's disease. In a case study, nobiletin-rich Citrus reticulata peels could prevent the progression of cognitive impairment in donepezil-preadministered Alzheimer's disease patients. Objective: In this study, we investigated the effects and underlying mechanism of nobiletin and Citrus unshiu immature peel (CUIP) water extract, which contains nobiletin as a major compound, on hydrogen peroxide-induced oxidative stress in HT22 cells, a murine hippocampal neuronal model. Materials and Methods: HT22 cells were treated with hydrogen peroxide in the presence or absence of various concentrations of CUIP and nobiletin. Cytotoxicity and apoptotic protein levels were measured by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and Western blotting. Results: Pretreatment with CUIP and nobiletin inhibited cell death due to hydrogen peroxide. Hydrogen peroxide-induced the expression of phospho-Jun N-terminal kinases (p-JNK) and p-p38 proteins in HT22 cells; however CUIP and nobiletin suppressed p-JNK and p-p38 without changing JNK or p38. Regarding apoptosis, caspase 3, B-cell lymphoma 2 (Bcl-2), and Bax protein expression was determined. CUIP and nobiletin suppressed caspase 3 and Bax expression, but they induced Bcl-2 expression in HT22 cells. Conclusion: These results show that CUIP and nobiletin can protect against hydrogen peroxide-induced cell death in HT22 neurons via mitogen-activated protein kinases and apoptotic pathways.

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