title: A Combination of Resveratrol and Curcumin is Effective Against Aluminum Chloride-Induced Neuroinflammation in Rats.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
authors.forename: Amira
authors.initials: A
authors.lastname: Zaky
authors.affiliation: Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Bassiouny
authors.affiliation: Department of Environmental Research at National Center for Social & Criminological Research, Giza, Egypt.
authors.forename: Mahitab
authors.initials: M
authors.lastname: Farghaly
authors.affiliation: Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Bassma M
authors.initials: BM
authors.lastname: El-Sabaa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002374:Catalase / Q000378:metabolism; D002712:Chlorides / Q000633:toxicity*; D003474:Curcumin / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004338:Drug Combinations; D004660:Encephalitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D004338:Drug Combinations; D018696:Neuroprotective Agents; D013267:Stilbenes; D000077410:Aluminum Chloride; D002374:Catalase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D000110:Acetylcholinesterase; D003474:Curcumin; D000077185:Resveratrol
keywords: Aluminum; apurinic/apyrimidinic endonuclease 1; curcumin; cyclooxygenase-2; microRNA Let-7c; resveratrol