Dina Sabah Al-saeed 1, Basma Talib Al-Sudani 2, Ghaith Ali Jasim 3
1Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Iraq
2Department of Clinical Laboratories Sciences, College of Pharmacy, Mustansiriyah University, Iraq,
3Department of Pharmacology and Toxicology, College of Pharmacy, Al-Bayan University, Iraq
ABSTRACT
Background: Inflammation is the body’s natural defense mechanism for removing noxious stimuli. According to the benzopyran substitutions, Coumarins are extensively dispersed in nature and have varied biological effects. Purpose: The purpose of this study is to estimate the anti-inflammatory effect of some Coumarin derivatives using RAW 264.7 macrophage cell lines including the inhibitory effect of these derivatives on cyclooxygenase-2 enzyme, interleukin-1β, and interleukin-6. Methods: In the present investigation, RAW 264.7 cells were treated with varying concentrations (0.15-100µM) of three Coumarin derivatives. After 72 hours, the half-maximal inhibitory concentration (IC50) was determined using the MTT assay to assess the cytotoxicity of these derivatives. The levels of cyclooxygenase-2, interleukin-1β, and interleukin-6 were also evaluated using the ELISA technique. Results: The half–maximal inhibitory concentrations for C1, C2, C3, and Diclofenac were 32 µM, 25.09 µM, 12.2 µM, and 30.42 µM, respectively. At concentrations 2.5, 5, 7.5, and 10 mg/ml of these derivatives, cyclooxygenase-2 activity was decreased significantly by C2 and C3 more than the Diclofenac (Reference compound) (p˂0.05). C2 and C3 significantly reduced the level of interleukin1β induced by lipopolysaccharide compared with the lipopolysaccharide alone (p˂0.05). The inhibitory effects of C1, C2 and C3 were significantly more potent on interleukin-6 level induced by lipopolysaccharide compared with lipopolysaccharide alone (p˂0.05).Conclusions: C2 and C3 had better anti-inflammatory effects than Diclofenac as they had a significantly higher inhibitory effect on the cyclooxygenase-2 activity than the inhibitory activity of Diclofenac and significantly inhibited interleukin-1β and interleukin-6 induced by lipopolysaccharide compared with the lipopolysaccharide (LPS) alone
Keywords:RAW264.7, Coumarin, Anti-inflammatory, Cyclooxygenase-2, Interleukins..