title: 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.
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea. yangkang@kaeri.re.kr.|College of Pharmacy, Chungnam National University, Daejeon, Chungcheongnam-do 34134, Korea. yangkang@kaeri.re.kr.
authors.forename: Yangkang
authors.initials: Y
authors.lastname: So
authors.affiliation: Freshwater Bioresources Utilization Division, Nakdonggang National Institute of Biological Resources, Sangju-si, Gyeongsangbuk-do 37242, Korea. nplsy001@nnibr.re.kr.
authors.forename: Seung Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea. arhan@kaeri.re.kr.
authors.forename: Ah-Reum
authors.initials: AR
authors.lastname: Han
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea. jbkim74@kaeri.re.kr.
authors.forename: Jin-Baek
authors.initials: JB
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Chungcheongnam-do 34134, Korea. hgjeong@cnu.ac.kr.
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 56212, Korea. chjin@kaeri.re.kr.
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Jin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002934:Cinnamates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D053630:Depsides / Q000737:chemistry / Q000494:pharmacology; D004952:Esters / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D000097123:Rosmarinic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D002934:Cinnamates; D016207:Cytokines; D053630:Depsides; D004952:Esters; D051547:Heme Oxygenase-1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D053594:Myeloid Differentiation Factor 88; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000097123:Rosmarinic Acid; C507780:Myd88 protein, mouse; C496317:Nos2 protein, mouse; C496542:Hmox1 protein, mouse
keywords: MyD88-dependent and -independent pathways; Perilla frutescens; anti-inflammation; heme oxygenase-1; rosmarinic acid methyl ester