title: Co-administration of 3-Acetyl-11-Keto-Beta-Boswellic Acid Potentiates the Protective Effect of Celecoxib in Lipopolysaccharide-Induced Cognitive Impairment in Mice: Possible Implication of Anti-inflammatory and Antiglutamatergic Pathways.
abstract: Neuro-inflammation is known to initiate the underlying pathogenesis of several neurodegenerative disorders which may progress to cognitive, behavioral, and functional impairment. Boswellia serrata is a well-known powerful anti-inflammatory agent used to treat several inflammatory diseases. The aim of the current study is to investigate the effect of the combination therapy of 3-acetyl-11-keto-β-boswellic acid (AKBA), a 5-lipoxygenase (5-LOX) inhibitor and celecoxib, and a selective cyclooxygenase-2 (COX-2) inhibitor as dual enzyme inhibitors compared to monotherapies with celecoxib and AKBA. Cognitive dysfunction is induced by intraperational injection of lipopolysaccharide (LPS) in mice. Radial maze, Y maze, and novel object recognition (NOR) were performed to evaluate the possible behavioral changes. Moreover, estimation of glutamate and tumor necrosis factor-alpha (TNF-α), as well as an immunohistochemical investigation of amyloid beta peptide (Aβ) was performed to evaluate the molecular changes that followed the LPS or drug treatment. The results showed that the combination therapy of AKBA and celecoxib reversed the behavioral and molecular changes caused by LPS cognitive dysfunction model that predispose cognitive dysfunction in mice. This study showed the effectiveness of the dual therapy with AKBA and celecoxib as anti-inflammatory, antiglutamatergic, and anti-amyloidogenic agents in the management of cognitive dysfunction.
authors.affiliation: Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo City, 11835, Egypt.
authors.forename: Aya Shoukry
authors.initials: AS
authors.lastname: Sayed
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza, 12613, Egypt. nesrine.elsayed@guc.edu.eg.|Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo City, 11835, Egypt. nesrine.elsayed@guc.edu.eg.
authors.forename: Nesrine Salah El Dine
authors.initials: NS
authors.lastname: El Sayed
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068579:Celecoxib / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D004357:Drug Synergism; D018698:Glutamic Acid / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D004338:Drug Combinations; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C094432:acetyl-11-ketoboswellic acid; D018698:Glutamic Acid; D000068579:Celecoxib
keywords: 3-Acetyl-11-keto-β-boswellic acid; Amyloid beta peptide; Cognitive dysfunction; Glutamate; Lipopolysaccharide; Tumor necrosis factor-alpha