title: Bryonolic acid transcriptional control of anti-inflammatory and antioxidant genes in macrophages in vitro and in vivo.
abstract: Bryonolic acid (BA) (1) is a naturally occurring triterpenoid with pleiotropic properties. This study characterizes the mechanisms mediating the anti-inflammatory and antioxidant activities of BA and validates the utility of BA as a tool to explore the relationships between triterpenoid structure and activity. BA reduces the inflammatory mediator NO by suppressing the expression of the inflammatory enzyme inducible nitric oxide synthase (iNOS) in LPS-activated RAW 264.7 macrophage cells. In addition, BA robustly induces the antioxidant protein heme oxygenase-1 (HO-1) in vitro and in vivo in an Nrf2-dependent manner. Further analyses of Nrf2 target genes reveal selectivity for the timing and level of gene induction by BA in treated macrophages with distinct patterns for Nrf2-regulated antioxidant genes. Additionally, the distinct expression profile of BA on Nrf2 target genes relative to oleanolic acid suggests the importance of the triterpenoid scaffold in dictating the pleiotropic effects exerted by these molecules.
authors.affiliation: Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Tonibelle N
authors.initials: TN
authors.lastname: Gatbonton-Schwager
authors.forename: John J
authors.initials: JJ
authors.lastname: Letterio
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Tochtrop
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051265:NF-E2-Related Factor 1 / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D051265:NF-E2-Related Factor 1; D014315:Triterpenes; D009569:Nitric Oxide; D009828:Oleanolic Acid; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C074984:bryonolic acid