Rosmanol Potently Inhibits Lipopolysaccharide-Induced iNOS and COX-2 Expression through Downregulating MAPK, NF-κB, STAT3 and C/EBP Signaling Pathways

• Published in: Journal of agricultural and food chemistry Vol. 57; no. 22; pp. 10990 - 10998
• Main Authors: Lai, Ching-Shu, Lee, Jong Hun, Ho, Chi-Tang, Liu, Cheng Bin, Wang, Ju-Ming, Wang, Ying-Jan, Pan, Min-Hsiung
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 25.11.2009
• Subjects: antioxidant activity; biochemical pathways; Biological and medical sciences; food analysis; Food Chemistry/Biochemistry; food composition; Food industries; Fundamental and applied biological sciences. Psychology; gene expression regulation; inhibitors; lipopolysaccharides; mitogen-activated protein kinase; nitric oxide synthase; nuclear factor-kappaB; polyphenols; prostaglandin synthase; protein synthesis; rosmanol; Rosmarinus officinalis; signal transduction; inducible NO synthase (iNOS); NF-κB; lipopolysaccharide (LPS); cyclooxygenase-2 (COX-2); RAW 264.7 monocyte/macrophages; Rosmanol; Monocyte; Lipopolysaccharide
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf9025713

Rosmanol is a natural polyphenol from the herb rosemary (Rosmarinus officinalis L.) with high antioxidant activity. In this study, we investigated the inhibitory effects of rosmanol on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells induced by lipopolysaccharide (LPS). Rosmanol markedly inhibited LPS-stimulated iNOS and COX-2 protein and gene expression, as well as the downstream products, NO and PGE2. Treatment with rosmanol also reduced translocation of the nuclear factor-κB (NF-κB) subunits by prevention of the degradation and phosphorylation of inhibitor κB (IκB). Western blot analysis showed that rosmanol significantly inhibited translocation and phosphorylation of NF-κB, signal transducer and activator of transcription-3 (STAT3), and the protein expression of C/EBPβ and C/EBPδ. We also found that rosmanol suppressed LPS-induced phosphorylation of ERK1/2, p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Our results demonstrate that rosmanol downregulates inflammatory iNOS and COX-2 gene expression by inhibiting the activation of NF-κB and STAT3 through interfering with the activation of PI3K/Akt and MAPK signaling. Taken together, rosmanol might contribute to the potent anti-inflammatory effect of rosemary and may have potential to be developed into an effective anti-inflammatory agent.