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Molecules 2016, 21(8), 1083; 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

1
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea
2
College of Pharmacy, Chungnam National University, Daejeon, Chungcheongnam-do 34134, Korea
3
Freshwater Bioresources Utilization Division, Nakdonggang National Institute of Biological Resources, Sangju-si, Gyeongsangbuk-do 37242, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Norbert Latruffe
Received: 12 July 2016 / Revised: 8 August 2016 / Accepted: 11 August 2016 / Published: 18 August 2016
(This article belongs to the Special Issue Natural Products and Inflammation)
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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. View Full-Text
Keywords: Perilla frutescens; anti-inflammation; rosmarinic acid methyl ester; MyD88-dependent and -independent pathways; heme oxygenase-1 Perilla frutescens; anti-inflammation; rosmarinic acid methyl ester; MyD88-dependent and -independent pathways; heme oxygenase-1
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

So, Y.; Lee, S.Y.; Han, A.-R.; Kim, J.-B.; Jeong, H.G.; Jin, C.H. 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. Molecules 2016, 21, 1083.

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