Neuroprotective effect of Citrus unshiu immature peel and nobiletin inhibiting hydrogen peroxide‑induced oxidative stress in HT22 murine hippocampal neuronal cells
Hyun Woo Cho1, Su Young Jung2, Gyeong Hwan Lee1, Jung Hee Cho1, In Young Choi1★★ Corresponding author
- 1Research and Development Team, Jeonnam Development Institute of Korean Traditional Medicine, 288 Udeuraendeu‑gil, Anyang‑myun Jangheung‑gun, Jeonnam 529‑851.
- 2Clinical Trial Center for Functional Foods, Chonbuk National University Hospital, Jeonju, 20, Geonjiro, Deokjin‑gu, Jeonju 561‑712, Republic of Korea.
CORRESPONDENCE
In Young Choi
Research and Development Team, Jeonnam Development Institute of Korean Traditional Medicine, 288 Udeuraendeu‑gil, Anyang‑myun Jangheung‑gun, Jeonnam 529‑851.
Received: 20-08-2014; Revised: 26-09-2014.
Volume 11, Issue 44s1 · pp. 284–289 · PUBLISHED 24 September 2015 · DOI: 10.4103/0973-1296.166047
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ABSTRACT
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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Cho, H. W., Jung, S. Y., Lee, G. H., Cho, J. H., & Choi, I. Y. (2015). Neuroprotective effect of Citrus unshiu immature peel and nobiletin inhibiting hydrogen peroxide‑induced oxidative stress in HT22 murine hippocampal neuronal cells. Pharmacognosy Magazine, 11(44s1), 284–289. https://doi.org/10.4103/0973-1296.166047