Inhibitory effect of DCDC on lipopolysaccharide-induced nitric oxide synthesis in RAW 264.7 cells

• Published in: Life sciences (1973) 2001-04, Vol.68 (21), p.2435-2447
• Main Authors: Huang, Yu-Chun, Guh, Jih-Hwa, Cheng, Zhi-Jiao, Chang, Ya-Ling, Hwang, Tsong-Long, Lin, Chun-Nan, Teng, Che-Ming
• Format: Article
• Language: English
• Subjects: Animals; Antioxidant; Antioxidants - pharmacology; Cell Line; Chalcone - analogs & derivatives; Chalcone - pharmacology; Chalcone - therapeutic use; Chalcones; COX-2; Cyclooxygenase 2; DCDC; Electrophoresis, Polyacrylamide Gel; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; I-kappa B Proteins - metabolism; Immunohistochemistry; Isoenzymes - metabolism; Lipopolysaccharide; Lipopolysaccharides - toxicity; Longevity - drug effects; Macrophages - cytology; Macrophages - drug effects; Macrophages - enzymology; Mice; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; Prostaglandin-Endoperoxide Synthases - metabolism; Shock, Septic - chemically induced; Shock, Septic - prevention & control
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(01)01035-9

In the present study we have examined the effect of DCDC (2′, 5′, -dihydroxy-4-chloro-dihydrochalcone) on lipopolysaccharide (LPS)-induced responses in murine macrophage cell line RAW 264.7. Exposure of LPS-stimulated cells to DCDC inhibited the nitrite accumulation in culture medium. DCDC also concentration-dependently inhibited LPS-stimulated increase of iNOS expression; however, it had little effect on iNOS enzyme activity, suggesting that the inhibitory action to DCDC is mainly due to the inhibition on iNOS expression rather than iNOS enzyme activity. DCDC significantly inhibited LPS-evoked degradation of IκB-α and the nuclear translocation of NF-κB; it also exhibited the activity of scavenging the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). DCDC also inhibited cyclooxygenase-2 activity in RAW 264.7 cells with an IC 50 of 3.0 μM; furthermore, it also significantly decreased LPS-induced mortality rate in mice. Taken together, we demonstrate that DCDC exhibits inhibitory effects on nitric oxide production through the inhibition of IκB-α degradation and NF-κB activation, and therefore the suppression of iNOS expression. DCDC also shows the antioxidant activity and COX-2 inhibitory action. Moreover, it improves survival in a murine model of endotoxaemia suggesting that DCDC may be potential in the therapy of septic shock.