Reference - Detail
|Author||Gatbonton-Schwager TN, Letterio JJ, Tochtrop GP.|
|Title||Bryonolic acid transcriptional control of anti-inflammatory and antioxidant genes in macrophages in vitro and in vivo.|
|Journal||J Nat Prod|
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.
|MeSH||Animals Anti-Inflammatory Agents / pharmacology Antioxidants / pharmacology* Dose-Response Relationship, Drug Heme Oxygenase-1 / drug effects* Lipopolysaccharides / pharmacology Macrophages / drug effects Macrophages / metabolism Macrophages / physiology* Mice Mice, Inbred C57BL NF-E2-Related Factor 1 / drug effects Nitric Oxide / biosynthesis Nitric Oxide Synthase Type II / analysis Nitric Oxide Synthase Type II / genetics Nitric Oxide Synthase Type II / metabolism Oleanolic Acid / chemistry Oleanolic Acid / pharmacology Triterpenes / chemistry Triterpenes / pharmacology*|
|WOS Category||PLANT SCIENCES PHARMACOLOGY & PHARMACY CHEMISTRY, MEDICINAL|
|Mice||Nrf2 knockout mouse/C57BL6J|