Rosmarinic Acid Methyl Ester Inhibits LPS-Induced NO Production via Suppression of MyD88- Dependent and -Independent Pathways and Induction of HO-1 in RAW 264.7 Cells
- PMID: 27548124
- PMCID: PMC6274143
- DOI: 10.3390/molecules21081083
Rosmarinic Acid Methyl Ester Inhibits LPS-Induced NO Production via Suppression of MyD88- Dependent and -Independent Pathways and Induction of HO-1 in RAW 264.7 Cells
Abstract
In this study, we investigated the anti-inflammatory effect of rosmarinic acid methyl ester (RAME) isolated from a mutant cultivar of Perilla frutescens (L.) Britton. We found that RAME inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with an IC50 of 14.25 µM, in RAW 264.7 cells. RAME inhibited the LPS-induced expression of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, interferon-β, and inducible nitric oxide synthase (iNOS). Moreover, RAME suppressed the activation of nuclear factor kappa B. These results suggest that the downregulation of iNOS expression by RAME was due to myeloid differentiation primary response gene 88 (MyD88)-dependent and -independent pathways. Furthermore, RAME induced the expression of heme oxygenase-1 (HO-1) through activation of nuclear factor-erythroid 2-related factor 2. Treatment with tin protoporphyrin, an inhibitor of HO-1, reversed the RAME-induced suppression of NO production. Taken together, RAME isolated from P. frutescens inhibited NO production in LPS-treated RAW 264.7 cells through simultaneous induction of HO-1 and inhibition of MyD88-dependent and -independent pathways.
Keywords: MyD88-dependent and -independent pathways; Perilla frutescens; anti-inflammation; heme oxygenase-1; rosmarinic acid methyl ester.
Conflict of interest statement
The authors declare no conflict of interest.
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References
-
- Kim K.N., Heo S.J., Yoon W.J., Kang S.M., Ahn G., Yi T.H., Jeon Y.J. Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-κB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages. Eur. J. Pharmacol. 2010;649:369–375. - PubMed
-
- Guzik T.J., Korbut R., Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J. Physiol. Pharmacol. 2003;54:469–487. - PubMed
-
- Nathan C. Points of control in inflammation. Nature. 2002;420:846–852. - PubMed
-
- Walsh N.C., Crotti T.N., Goldring S.R., Gravallese E.M. Rheumatic diseases: The effects of inflammation on bone. Immunol. Rev. 2005;208:228–251. - PubMed
-
- Lee H.J., Hyun E.A., Yoon W.J., Kim B.H., Rhee M.H., Kang H.K., Cho J.Y., Yoo E.S. In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts. J. Ethnopharmacol. 2006;103:208–216. - PubMed
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