title: Association of Neuroprotective Effect of Di-O-Demethylcurcumin on Aβ25-35-Induced Neurotoxicity with Suppression of NF-κB and Activation of Nrf2.
abstract: Amyloid-β peptides (Aβ), 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 Aβ-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 Aβ-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-κB (NF-κB) 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 IκBα, translocation of the p65 subunit of NF-κB 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-κB and activate Nrf2 signaling pathways induced by Aβ25-35.
authors.affiliation: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors.forename: Decha
authors.initials: D
authors.lastname: Pinkaew
authors.affiliation: Division of Physical Science, Faculty of Science and Technology, Huachiew Chalermprakiet University, Samutprakarn, 10540, Thailand.
authors.forename: Chatchawan
authors.initials: C
authors.lastname: Changtam
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors.forename: Chainarong
authors.initials: C
authors.lastname: Tocharus
authors.affiliation: Institute of Molecular Biosciences, Research Center for Neuroscience, Mahidol University, Bangkok, Thailand.
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
authors.affiliation: Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors.forename: Pichaya
authors.initials: P
authors.lastname: Jumnongprakhon
authors.affiliation: Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, 10240, Thailand.
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.affiliation: Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. jtocharus@gmail.com.
authors.forename: Jiraporn
authors.initials: J
authors.lastname: Tocharus
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D009573:Nitrites; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D003474:Curcumin
keywords: Alzheimer’s disease; Amyloid-β peptides; Di-O-demethylcurcumin; Nuclear factor erythroid 2-related factor 2; Nuclear factor-κB; Oxidative stress