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.

Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells

“…Importantly, melatonin could promote the expression and Nrf2 activity, and this promotion was closely involved with NOX2 devoid of NF-κB signaling. In contrast, a few studies have demonstrated that the inhibition of NF-κB signaling could promote Nrf2 activity (Wijayanti et al, 2004;Pinkaew et al, 2015). Thus, we suggest that the activation of Nrf2 in the brain endothelial cells may be closely related with NOX2 signaling rather than NF-κB signaling because the NF-κB signaling may be a parallel cascade during inflammation.…”

Blautia—a new functional genus with potential probiotic properties?

“…74 Compared with curcumin, demethylcurcumin has been found to be highly toxic to human HCT116 colon cancer cells, whereas synthetic desmethylcurcumin has been found to exert better neuroprotective and antiinflammatory effects. [75][76][77] Furthermore, the strain Blautia sp. AUH-JLD56 has been shown to specifically and efficiently biotransform arctiin or arctigenin to (−)-3′-desmethyl arctigenin, which possesses good free radical-scavenging activity.…”

Interaction between Gut Microbiota and Curcumin: A New Key of Understanding for the Health Effects of Curcumin

“…Eight metabolites of curcumin were identified (bisdemethylated hexahydrocurcumin, demethylated and dehydroxylated hexahydrocurcumin, demethylcurcumin, demethylated and demethoxylated curcumin, hydroxylatedcurcumin, dihydrocurcumin, hexahydrocurcumin, and demethylated hexahydrocurcumin). It is important to highlight that many of these metabolites have been reported to exhibit neuroprotective ability [131][132][133].…”