RRC ID 16022
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.
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.
Volume 75(4)
Pages 591-8
Published 2012-4-27
DOI 10.1021/np200823p
PMID 22339499
PMC PMC4089864
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*
IF 3.885
Times Cited 3
WOS Category PLANT SCIENCES PHARMACOLOGY & PHARMACY CHEMISTRY, MEDICINAL
Resource
Mice Nrf2 knockout mouse/C57BL6J