Inhibitory effects of indole α-lipoic acid derivatives on nitric oxide production in LPS/IFNγ activated RAW 264.7 macrophages.
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.
Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
Arzu Zeynep
AZ
Karabay
Aslı
A
Koc
A Selen
AS
Gurkan-Alp
Zeliha
Z
Buyukbingol
Erdem
E
Buyukbingol
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D007371:Interferon-gamma / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D008063:Thioctic Acid / Q000737:chemistry / Q000494:pharmacology*
D016207:Cytokines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D008063:Thioctic Acid; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II
RAW 264.7; iNOS; indole; inflammation; α-lipoic acid