Association of Neuroprotective Effect of Di-O-Demethylcurcumin on A beta(25-35)-Induced Neurotoxicity with Suppression of NF-kappa B and Activation of Nrf2

作者：Pinkaew Decha; Changtam Chatchawan; Tocharus Chainarong; Govitrapong Piyarat; Jumnongprakhon Pichaya; Suksamrarn Apichart; Tocharus Jira****^*

来源：Neurotoxicity Research, 2016, 29(1): 80-91.

DOI：10.1007/s12640-015-9558-4

• Alzheimer's disease
• Amyloid-beta peptides
• Di-O-demethylcurcumin
• Nuclear factor-kappa B
• Nuclear factor erythroid 2-related factor 2
• Oxidative stress

Amyloid-beta peptides (A beta), a major component of senile plaques, play an important role in the development and progression of Alzheimer's disease. Several lines of evidence have demonstrated that A beta-induced neuronal death is mediated by oxidative stress. The present study aimed to evaluate the potential involvement of di-O-demethylcurcumin, an analog of curcuminoid, on A beta-induced neurotoxicity in culture neuroblastoma cells (SK-N-SH cells) through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the suppression of nuclear factor-kappa B (NF-kappa B) signaling pathway and their downstream targets. The results showed that pretreatment with di-O-demethylcurcumin elevated cell viability and decreased the level of reactive oxygen species. Moreover, treatment with di-O-demethylcurcumin promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus, increased the expression of Nrf2-ARE pathway-related downstream proteins including heme oxygenase (HO-1), NAD(P)H:quinone oxidoreductase 1 and glutamate-cysteine ligase catalytic subunit, and increased the activity of superoxide dismutase enzymes. On the other hand, di-O-demethylcurcumin suppressed the degradation of I kappa B alpha, translocation of the p65 subunit of NF-kappa B from cytoplasm to nucleus and thereby, attenuated the expression of inducible nitric oxide synthase protein and nitric oxide production. Taken together, these results suggest that neuroinflammatory effect of di-O-demethylcurcumin might potentially be due to inhibit NF-kappa B and activate Nrf2 signaling pathways induced by A beta(25-35).

• 出版日期2016-1