title: A hot water extract of Aralia cordata activates bone marrow-derived macrophages via a myeloid differentiation protein 88-dependent pathway and protects mice from bacterial infection.
abstract: In traditional Asian medicine, Aralia cordata (AC) is a known as a pain reliever and anti-inflammatory drug. Although several of its biological activities have been reported, the immunomodulatory effects of a hot water extract of AC (HAC) have not yet been described. The aim of this study was to investigate whether HAC modulates the activation of macrophages, which play important roles in innate immune responses against microbial pathogens, and if so, to determine the molecular mechanisms by which HAC mediates this process. It was found that HAC activates bone marrow-derived macrophages (BMDM) and increases amounts of nitric oxide and proinflammatory cytokines in a dose-dependent manner. In addition, HAC was found to induce phosphorylation of NF-κB and mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinases, extracellular signal-regulated kinases and p38. Interestingly, these effects were absent in BMDM prepared from myeloid differentiation protein 88-knockout mice. Polysaccharides from HAC exerted stronger immunostimulatory effects than HAC itself. Furthermore, orally administered HAC clearly enhanced clearance of the intracellular pathogen Listeria monocytogenes by boosting innate immune responses. These results demonstrate that HAC exerts immunostimulatory effects through the TLR/MyD88 and NF-κB/MAPK signal transduction pathways.
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresources, Chonbuk National University, Iksan-si, Jeollabuk-do, 54596.
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Seo
authors.affiliation: National Institute of Animal Science, Rural Development Administration, Cheonan-si, Chungcheongnam-do, 441-706, South Korea.
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Cho
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresources, Chonbuk National University, Iksan-si, Jeollabuk-do, 54596.
authors.forename: Suna
authors.initials: S
authors.lastname: Gu
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresources, Chonbuk National University, Iksan-si, Jeollabuk-do, 54596.
authors.forename: Da-Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresources, Chonbuk National University, Iksan-si, Jeollabuk-do, 54596.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresources, Chonbuk National University, Iksan-si, Jeollabuk-do, 54596.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Yi
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresources, Chonbuk National University, Iksan-si, Jeollabuk-do, 54596.
authors.forename: Sang-Myeong
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D027983:Aralia / Q000737:chemistry*; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational
chemical_list: D007155:Immunologic Factors; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010936:Plant Extracts; D020928:Mitogen-Activated Protein Kinases
keywords: Aralia cordata; immunostimulatory effect; macrophages; myeloid differentiation protein 88