title: Potent Anti-inflammatory and Analgesic Actions of the Chloroform Extract of Dendropanax morbifera Mediated by the Nrf2/HO-1 Pathway.
abstract: Dendropanax morbifera LEVEILLE (DP) has been used in traditional Korean medicines to treat a variety of inflammatory diseases. Although the in vitro anti-inflammatory potential of this plant is understood, its in vivo efficacy and underlying molecular mechanism of anti-inflammatory effects are largely unknown. We elucidated the anti-inflammatory and analgesic activities and the underlying molecular mechanisms of DP using in vitro and in vivo models. Lipopolysaccharide (LPS)-stimulated murine macrophages were used to analyze the in vitro anti-inflammatory potential of DP extract and to elucidate the underlying mechanisms. In vivo animal models of phorbol 12-myristate 13-acetate (TPA)-induced ear edema and acetic acid-induced writhing response tests were used to analyze the in vivo anti-inflammatory effects and anti-nociceptive effects of DP extract, respectively. Methanolic extract of DP (DPME) significantly inhibited the release of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-activated macrophages. Among the five sub-fractions, the chloroform fraction (DP-C) showed the most potent suppressive effects against pro-inflammatory mediators and cytokines in LPS-stimulated macrophages. These effects were attributed to inhibition of nuclear factor-κB (NF-κB) nuclear translocation and c-Jun N terminal kinase (JNK) 1/2 phosphorylation and to activation of NF-E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling. DP-C exhibited strong protective in vivo effects in TPA-induced ear edema mouse model and acetic acid-induced writhing response test. Our data suggest that DP-C has potent anti-inflammatory and analgesic activities and may be a promising treatment against a variety of inflammatory diseases.
authors.affiliation: College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Akram
authors.forename: Kyeong-A
authors.initials: KA
authors.lastname: Kim
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Kim
authors.forename: Ahmed Shah
authors.initials: AS
authors.lastname: Syed
authors.forename: Chul Young
authors.initials: CY
authors.lastname: Kim
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D027481:Araliaceae; D002725:Chloroform / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D018515:Plant Leaves; D000067996:RAW 264.7 Cells; D012997:Solvents / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D009573:Nitrites; D010936:Plant Extracts; D012997:Solvents; D002725:Chloroform; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048670:MAP Kinase Kinase 4; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D019342:Acetic Acid