title: N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide decreases triglyceride levels by downregulation of Apoc3 gene expression in acute hyperlipidemic rat model.
abstract: Hyperlipidemia is a known cause of coronary vascular diseases, which is a major cause of death in many parts of the world. Targeting several pathways that lead to increase in lipid profiles is of great potential to control diseases. 1H-indole-2-carboxamide derivatives were tested for their hypolipidemic activity at the molecular level in comparison with bezafibrate. The gene expression profiles of lipoprotein signaling and cholesterol metabolism and fatty acid metabolism PCR arrays were determined in rats with acute hyperlipidemia induced by Triton WR1339. Lipid profiles of serum from treated rats showed significant hypolipidemic effect by the compounds. Several genes of potential interest were reported to be overexpressed by Triton WR1339 including Apoc3, Apob, Hmgcs2, Apoa1, Apoe, Apof, acsl1, and Decr1. Most of the overexpressed genes were downregulated by N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide with significant decreases in Apoc3, Apob, Acaa2, Acsl1, and Slc247a5 gene expression levels. N-(4-Benzoylphenyl)-1H-Indole-2-Carboxamide and bezafibrate did not significantly affect the gene expression levels which were increased with acute hyperlipidemia induced by Triton WR1339. In conclusion, gene expression profiling identified the possible mechanism in which Triton WR1339 induces its acute hyperlipidemic effect which was reversed by the use of N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide.
authors.affiliation: Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan. lama.hamadneh@zuj.edu.jo.
authors.forename: Lama
authors.initials: L
authors.lastname: Hamadneh
authors.affiliation: Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Luay
authors.initials: L
authors.lastname: Al-Essa
authors.affiliation: Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Suhair
authors.initials: S
authors.lastname: Hikmat
authors.affiliation: Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Tariq
authors.initials: T
authors.lastname: Al-Qirim
authors.affiliation: Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Abu Sheikha
authors.affiliation: Faculty of Pharmacy, The University of Jordan, Amman, 11942, Jordan.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Al-Hiari
authors.affiliation: Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman, 11733, Jordan.
authors.forename: Nisrin
authors.initials: N
authors.lastname: Azmy
authors.affiliation: King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Shattat
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000096:biosynthesis*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011092:Polyethylene Glycols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood*
chemical_list: D053305:Apolipoprotein C-III; D007093:Imidazoles; D014280:Triglycerides; D011092:Polyethylene Glycols; C016811:tyloxapol
keywords: Apoc3; HDL; Hyperlipidemia; Indole-2-carboxamide derivatives; Triglycerides; Triton WR1339