Affiliations: [a] Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt
| [b] Department of Environmental Research at National Center for Social & Criminological Research, Giza, Egypt
| [c] Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
Correspondence:
[*]
Correspondence to: Amira Zaky, Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Moharram Bake, P.O Box 21511, Egypt. Tel.: +20 1223584529; Fax: +20 203 3911794; E-mail: [email protected].
Abstract: Background:Experimental studies have demonstrated that aluminum is an environmental toxin that induces neuroinflammation and the development of Alzheimer’s disease. Objective:In this report, we investigated the beneficial effect of a combination of resveratrol and curcumin to reduce aluminum-induced neuroinflammation. Method:We employed both an in vivo model of aluminum-induced neuroinflammation and an in vitro aluminum stimulated cultured PC-12 cells. Neuroinflammation in rats was assessed by measuring the expression of β-secretase, amyloid-β protein precursor, and γ-subunits (PS-1 and PS-2), along with the inflammatory COX-2, Il-1β, Il-1α, and TNF-α. Furthermore, we measured the expression profiles of neuro-protective Apurinic/apyrimidinic endonuclease 1 (APE1) protein and let-7c microRNA. In parallel, PC-12 cells were treated with 0.5 mM aluminum to induce a neuroinflammation-like state. In addition, curcumin effect, as a selective COX-2 expression inhibitor, was detected in a time course manner. Results:An overall significant attenuation of the inflammatory markers, as well as a decrease in the amyloidogenic mediators, was observed in resveratrol-curcumin treated rats. The therapeutic effect was also confirmed by transmission electron microscopic analysis of the brain cortexes. APE1 was significantly induced by resveratrol-curcumin combination. Both in vivo and in vitro studies indicated that Let-7c expression is significantly reduced after aluminum stimulation, an effect that was partially suppressed by co-addition of either resveratrol or curcumin and totally restored to the normal level by their combination. Conclusions:The present study clearly indicates the synergistic and therapeutic effect of a resveratrol-curcumin combination. We also show that both compounds exert beneficial effect either cooperatively or through differential molecular mechanisms in counteracting aluminum-induced neuroinflammation.
