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N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide decreases triglyceride levels by downregulation of Apoc3 gene expression in acute hyperlipidemic rat model

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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.

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References

  1. Wadhera RK, Steen DL, Khan I, Giugliano RP, Foody JM (2016) A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. J Clin Lipidol 10(3):472–489. doi:10.1016/j.jacl.2015.11.010

    Article  PubMed  Google Scholar 

  2. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S. (2013) Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev doi:10.1002/14651858

    Google Scholar 

  3. Geldenhuys WJ, Lin L, Darvesh AS, Sadana P (2016) Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases. Drug Discov Today. doi:10.1016/j.drudis.2016.10.007

    PubMed  Google Scholar 

  4. Luo M, Peng D (2016) The emerging role of apolipoprotein C-III: beyond effects on triglyceride metabolism. Lipids Health Dis 15(1):184

    Article  PubMed  PubMed Central  Google Scholar 

  5. Al-Hiari Y, Shattat G, Al-Qirim T, El-Huneidi W, Sheikha GA, Hikmat S (2011) Antihyperlipidemic properties of novel N-(benzoylphenyl)-5-substituted-1H-indole-2-carboxamides in Triton WR-1339-induced hyperlipidemic rats. Molecules 16(10):8292–8304. doi:10.3390/molecules16108292

    Article  CAS  PubMed  Google Scholar 

  6. Shahwan M, Shattat G, Al-Qirim T, Sheikha GA, Al-Hiari Y, El-Huneidi W, Jarab A, Al-Najdawi M (2010) Synthesis and pharmacological evaluation of novel substituted and unsubstituted N-(benzoylphenyl)-1H-indole-2-carboxamides as potent antihypertriglyceridemic agents. Z Naturforsch C. 65(5–6):309–316

    CAS  PubMed  Google Scholar 

  7. Al-Najdawi M, Al-Hiari Y, Al-Qirim T, Shattat G, Al-Zweri M, Abu Sheikha G (2014) Synthesis and pharmacological evaluation of novel unsubstituted indole-anthraquinone carboxamide derivatives as potent antihyperlipidemic agents. Z Naturforsch C 69(1–2):21–28

    Article  CAS  PubMed  Google Scholar 

  8. Yang Z, Cappello T, Wang L. (2015) Emerging role of microRNAs in lipid metabolism. Acta Pharm Sin B 5(2):145–150. doi:10.1016/j.apsb.2015.01.002

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sahebkar A, Watts GF (2013) New therapies targeting apoB metabolism for high-risk patients with inherited dyslipidaemias: what can the clinician expect? Cardiovasc Drugs Ther 27(6):559–567. doi:10.1007/s10557-013-6479-4

    Article  CAS  PubMed  Google Scholar 

  10. Nayak P, Panda S, Thatoi PK, Rattan R, Mohapatra S, Mishra PK (2016) Evaluation of lipid profile and apolipoproteins in essential hypertensive patients. J Clin Diagn Res 10(10):BC01–BC04

    PubMed  PubMed Central  Google Scholar 

  11. Wang YJ, Sun JB, Li F, Zhang SW (2006) Hyperlipidemia intensifies cerulein-induced acute pancreatitis associated with activation of protein kinase C in rats. World J Gastroenterol 12(18):2908–2913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zheng C (2014) Updates on apolipoprotein CIII: fulfilling promise as a therapeutic target for hypertriglyceridemia and cardiovascular disease. Curr Opin Lipidol 25(1):35–39. doi:10.1097/MOL.0000000000000040

    Article  CAS  PubMed  Google Scholar 

  13. Kawakami A, Yoshida M (2009) Apolipoprotein CIII links dyslipidemia with atherosclerosis. J Atheroscler Thromb 16(1):6–11

    Article  CAS  PubMed  Google Scholar 

  14. Norata GD, Tsimikas S, Pirillo A, Catapano AL (2015) Apolipoprotein C-III: from pathophysiology to pharmacology. Trends Pharmacol 36(10):675–687 doi:10.1016/j.tips.2015.07.001

    Article  CAS  Google Scholar 

  15. Liu X, Liu J, Liang S, Schlüter A, Fourcade S, Aslibekyan S, Pujol A, Graf GA (2014) ABCD2 alters peroxisome proliferator-activated receptor α signaling in vitro, but does not impair responses to fenofibrate therapy in a mouse model of diet-induced obesity. Mol Pharmacol 86(5):505–513. doi:10.1124/mol.114.092742

    Article  PubMed  PubMed Central  Google Scholar 

  16. Khetarpal SA, Qamar A, Millar JS, Rader DJ (2016) Targeting ApoC-III to reduce coronary disease risk. Curr Atheroscler Rep 18(9):54. doi:10.1007/s11883-016-0609-y

    Article  PubMed  Google Scholar 

  17. Libby P (2015) Triglycerides on the rise: should we swap seats on the seesaw? Eur Heart J 36(13):774–776

    Article  PubMed  Google Scholar 

  18. Pollin TI, Damcott CM, Shen H, Ott SH, Shelton J, Horenstein RB, Post W, McLenithan JC, Bielak LF, Peyser PA, Mitchell BD, Miller M, O’Connell JR, Shuldiner AR (2008) A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 322:1702–1705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jensen MK, Rimm EB, Furtado JD, Sacks FM. (2012) Apolipoprotein C-III as a potential modulator of the association between HDL-cholesterol and incident coronary heart disease. J Am Heart Assoc 1:jah3–e000232. doi:10.1161/JAHA.111.000232

    Article  PubMed  PubMed Central  Google Scholar 

  20. Doege H, Baillie RA, Ortegon AM, Tsang B, Wu Q, Punreddy S, Hirsch D, Watson N, Gimeno RE, Stahl A (2006) Targeted deletion of FATP5 reveals multiple functions in liver metabolism: alterations in hepatic lipid homeostasis. Gastroenterology 130(4):1245–1258

    Article  CAS  PubMed  Google Scholar 

  21. Anderson CM, Stahl A (2013) SLC27 fatty acid transport proteins. Mol Aspects Med 34(2–3):516–528. doi:10.1016/j.mam.2012.07.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sodhi SS, Ghosh M, Song KD, Sharma N, Kim JH, Kim NE, Lee SJ, Kang CW, Oh SJ, Jeong DK (2014) An approach to identify SNPs in the gene encoding acetyl-CoA acetyltransferase-2 (ACAT-2) and their proposed role in metabolic processes in pig. PLoS One 9(7):e102432. doi:10.1371/journal.pone.0102432 (eCollection)

    Article  PubMed  PubMed Central  Google Scholar 

  23. Rudel LL, Lee RG, Parini P (2005) ACAT2 is a target for treatment of coronary heart disease associated with hypercholesterolemia. Arterioscler Thromb Vasc Biol 25(6):1112–1118

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Lama Hamadneh.

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Hamadneh, L., Al-Essa, L., Hikmat, S. et al. N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide decreases triglyceride levels by downregulation of Apoc3 gene expression in acute hyperlipidemic rat model. Mol Cell Biochem 431, 133–138 (2017). https://doi.org/10.1007/s11010-017-2983-3

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  • DOI: https://doi.org/10.1007/s11010-017-2983-3

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