Abstract
Alpha-lipoic acid (α-lipoic acid) is a potent antioxidant compound that has been shown to possess anti-inflammatory effects. RAW 264.7 macrophages produce various inflammatory mediators such as nitric oxide, IL-1β, IL-6 and TNF-alpha upon activation with LPS (Lipopolysaccharide) and IFNγ (interferon gamma). In this study, the effect of 12 synthetic indole α-lipoic acid derivatives on nitric oxide production and iNOS (inducible nitric oxide synthase) protein expression in LPS/IFNγ activated RAW 264.7 macrophages was determined. Cell proliferation, nitric oxide levels and iNOS protein expression were examined with thiazolyl blue tetrazolium blue test, griess assay and western blot, respectively. Our results showed that all of the indole α-lipoic acid derivatives showed significant inhibitory effects on nitric oxide production and iNOS protein levels (p < 0.05). The most active compounds were identified as compound I-4b, I-4e and II-3b. In conclusion, these indole α-lipoic acid derivatives may have the potential for treatment of inflammatory conditions related with high nitric oxide production.
References
Oct 20, 1992·Biochemical Pharmacology·V E KaganL Packer
Nov 6, 1991·Biochemical Pharmacology·G R Haenen, A Bast
Jan 1, 1991·Free Radical Research Communications·Y J SuzukiL Packer
May 22, 1990·Biochimica Et Biophysica Acta·L Müller, H Menzel
Nov 27, 1980·Nature·R F Furchgott, J V Zawadzki
Dec 16, 1983·Journal of Immunological Methods·T Mosmann
Feb 1, 1994·Free Radical Research·B C ScottB Halliwell
May 14, 1994·Lancet·E Anggård
Jan 1, 1997·Annual Review of Immunology·J MacMickingC Nathan
Jun 15, 1999·Circulation·H Drexler
Mar 10, 2001·Biochemical Pharmacology·Q GuoL Packer
Sep 30, 2004·Free Radical Research·Vincent G DemarcoJeffrey W Skimming
Mar 15, 2005·Archiv der Pharmazie·A Selen GurkanErdem Buyukbingol
Feb 4, 2006·Current Topics in Medicinal Chemistry·Alan C Tinker, Alan V Wallace
Jul 10, 2007·British Journal of Pharmacology·B de las HerasL Boscá
Aug 2, 2012·Biogerontology·Ishita Guha ThakurtaSasanka Chakrabarti
Sep 22, 2012·Neurochemistry International·Mariana AstizCarlos Alberto Marra
Aug 6, 2013·Biological & Pharmaceutical Bulletin·Gwanpyo KohDae-Ho Lee
Sep 4, 2014·BMC Complementary and Alternative Medicine·Chiranjit GhoshSeong Gu Hwang
Nov 5, 2014·Integrative Biology : Quantitative Biosciences From Nano to Macro·Ling YuZhisong Lu
Dec 3, 2014·Bioorganic & Medicinal Chemistry Letters·Young Hwa SeoJong-Gab Jun
Citations
Oct 24, 2015·Bioorganic & Medicinal Chemistry Letters·Panagiotis Theodosis-NobelosEleni A Rekka
Oct 21, 2017·Inflammopharmacology·Talita SartoriRicardo Ambrósio Fock
Nov 10, 2016·Human & Experimental Toxicology·A A KhalafA Hassan
Oct 30, 2019·International Journal of Molecular Medicine·Dukhyun HwangGun-Do Kim
Feb 24, 2018·Pharmacological Reports : PR·Ártur Krumberg SchüllerMara Silveira Benfato