Bryonolic Acid Transcriptional
Control of Anti-inflammatory
and Antioxidant Genes in Macrophages in Vitro and in Vivo
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Abstract
Bryonolic acid (BA) (<b>1</b>) 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