Jatrorrhizine Protects Against Okadaic Acid Induced Oxidative Toxicity Through Inhibiting the Mitogen-Activated Protein Kinases Pathways in HT22 Hippocampal Neurons

Author(s): Wei Jiang , Wen-Biao Duan , Sheng Li , Xiu-Yin Shen , Yue Zhou , Tao Luo , Feng He , Jie Xu , Hua-Qiao Wang .

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 14 , Issue 10 , 2015

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Abstract:

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by deposit of amyloid plaques and neurofibrillary tangles and oxidative stress plays an essential role in the pathogenesis of AD. Jatrorrhizine (JAT), a Coptidis Rhizome, has multiple biological functions such as anti-oxidation and anti-inflammation. Herein, we investigated the neuroprotective effects of JAT on okadaic acid (OA)- induced cytotoxicity and apoptosis in HT22 cells. Following the exposure to 80nmol/L OA for 12h, the reduction in cell survival, activities of superoxide dismutase, glutathione peroxidase and mitochondria membrane potential has been shown in HT22 cells. In contrast, OA increased levels of lactate dehydrogenase, malondialdehyde production and intracellular reactive oxygen species. OA also enhanced the expression of Bax but decreased the levels of Bcl-2, OA also upregulated the expression of cleaved caspase-3, phosphorylated extracellular signal-regulated kinases 1/2, phosphorylated c-Jun Nterminal kinases, phosphorylated p38 and NF-kappa B p65 subunit in HT22 cells and this up-regulation was attenuated by JAT which was pre-incubated for 12h in the cells prior to OA exposure. In conclusion, our data present the protective role of JAT in OA induced cytotoxicity, via its antioxidant and anti-apoptotic properties by inhibiting the mitogen-activated protein kinases pathways in HT22 hippocampal neurons. These results indicate that JAT may be the potential target to treat AD induced by oxidative stress and apoptosis.

Keywords: Jatrorrhizine, HT22 cells, okadaic acid, oxidative stress, apoptosis.

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Article Details

VOLUME: 14
ISSUE: 10
Year: 2015
Page: [1334 - 1342]
Pages: 9
DOI: 10.2174/1871527314666150821104455
Price: $58

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