title: A comparative study of curcuminoids to measure their effect on inflammatory and apoptotic gene expression in an Aβ plus ibotenic acid-infused rat model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder, which depicts features of chronic inflammatory conditions resulting in cellular death and has limited therapeutic options. We aimed to explore the effect of a curcuminoid mixture and its individual components on inflammatory and apoptotic genes expression in AD using an Aβ+ibotenic acid-infused rat model. After 5 days of treatment with demethoxycurcumin, hippocampal IL-1β levels were decreased to 118.54 ± 47.48 and 136.67 ± 31.96% respectively at 30 and 10mg/kg, compared with the amyloid treated group (373.99 ± 15.28%). After 5 days of treatment, the curcuminoid mixture and demethoxycurcumin effectively decreased GFAP levels in the hippocampus. When studied for their effect on apoptotic genes expression, the curcuminoid mixture and bisdemethoxycurcumin effectively decreased caspase-3 level in the hippocampus after 20 days of treatment, where bisdemethoxycurcumin showed a maximal rescuing effect (92.35 ± 3.07%) at 3mg/kg. The curcuminoid mixture at 30 mg/kg decreased hippocampal FasL level to 70.56 ± 3.36% after 5 days of treatment and 19.01 ± 2.03% after 20 days. In the case of Fas receptor levels, demethoxycurcumin decreased levels after 5 days of treatment with all three doses showing a maximal effect (189.76 ± 15.01%) at 10mg/kg. Each compound was effective after 20 days in reducing Fas receptor levels in the hippocampus. This study revealed the important effect of curcuminoids on genes expression, showing that, each component of the curcuminoid mixture distinctly affects gene expression, thus highlighting the therapeutic potential of curcuminoids in AD.
authors.affiliation: Natural Products Research Unit, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi-Pakistan.
authors.forename: Touqeer
authors.initials: T
authors.lastname: Ahmed
authors.forename: Anwarul-Hassan
authors.initials: AH
authors.lastname: Gilani
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007051:Ibotenic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018690:Excitatory Amino Acid Agonists; D053222:Fas Ligand Protein; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C078592:amyloid beta-protein (1-40); D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D007051:Ibotenic Acid; D051546:Cyclooxygenase 2; D053148:Caspase 3; D003474:Curcumin