Synergistic Anti-inflammatory Effects of Nobiletin and Sulforaphane in Lipopolysaccharide-Stimulated RAW 264.7 Cells

• Published in: Journal of agricultural and food chemistry Vol. 60; no. 9; pp. 2157 - 2164
• Main Authors: Guo, Shanshan, Qiu, Peiju, Xu, Guang, Wu, Xian, Dong, Ping, Yang, Guanpin, Zheng, Jinkai, McClements, David Julian, Xiao, Hang
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 07.03.2012
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cell Line; Cyclooxygenase 2 Inhibitors - pharmacology; Drug Synergism; Flavones - pharmacology; Food industries; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Heme Oxygenase-1 - analysis; Heme Oxygenase-1 - genetics; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - genetics; Isothiocyanates; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Mice; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - antagonists & inhibitors; Thiocyanates - pharmacology; iNOS; sulforaphane; nitric oxide; nobiletin; COX-2; inflammation; Nitric oxide; Antiinflammatory agent; Lipopolysaccharide; Inflammation; Cell
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf300129t

Inflammation plays important roles in the initiation and progress of many diseases including cancers in multiple organ sites. Herein, we investigated the anti-inflammatory effects of two dietary compounds, nobiletin (NBN) and sulforaphane (SFN), in combination. Noncytotoxic concentrations of NBN, SFN, and their combinations were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that combined NBN and SFN treatments produced much stronger inhibitory effects on the production of nitric oxide (NO) than NBN or SFN alone at higher concentrations. These enhanced inhibitory effects were synergistic based on the isobologram analysis. Western blot analysis showed that combined NBN and SFN treatments synergistically decreased iNOS and COX-2 protein expression levels and induced heme oxygenase-1 (HO-1) protein expression. Real-time polymerase chain reaction analysis indicated that low doses of NBN and SFN in combination significantly suppressed LPS-induced upregulation of IL-1 mRNA levels and synergistically increased HO-1 mRNA levels. Overall, our results demonstrated that NBN and SFN in combination produced synergistic effects in inhibiting LPS-induced inflammation in RAW 264.7 cells.