Abstract
Oroxylin A, a natural flavonoid, is one of the main bioactive compounds that underlie the anti-inflammatory effect of the medicinal herb Scutellaria baicalensis Georgi widely used in southeastern Asia; however, the molecular mechanisms for the therapeutic benefits remain largely unclear. In this study, we found that Oroxylin A induces estrogen-responsive gene expression and promoter activity. In macrophages, Oroxylin A treatment significantly attenuates lipopolysaccharide (LPS)-induced but not basal inflammatory response, including nitric oxide (NO) production and the expression of inflammatory mediators (i.e., iNOS and COX-2) and cytokines (i.e., TNF-α, IL-1β, and IL-6), in an estrogen receptor (ER)-dependent manner. Oroxylin A treatment also dramatically decreases LPS-induced secretion of pro-inflammatory cytokines. Furthermore, the downregulation of all these inflammatory parameters by Oroxylin A was abolished when cells were pretreated with specific ER antagonist. Thus, Oroxylin A is a novel phytoestrogen and exhibits anti-inflammatory effects that are mediated by ER activity.
Highlights
Oroxylin A (C16H12O5, Figure S1) is one of the main bioactive compounds purified from the root of the medicinal herb Scutellaria baicalensis Georgi that has been widely used in China, Japan, and Korea for treating inflammation and infections in the respiratory and gastrointestinal system [1]
We found that Oroxylin A is a new phytoestrogen that activates estrogen-responsive promoter activity and the expression of endogenous estrogen target genes
Our results indicate that Oroxylin A displays a potent anti-inflammatory activity, attenuating LPS-induced expression of pro-inflammatory mediators and cytokines in macrophages
Summary
Oroxylin A (C16H12O5, Figure S1) is one of the main bioactive compounds purified from the root of the medicinal herb Scutellaria baicalensis Georgi that has been widely used in China, Japan, and Korea for treating inflammation and infections in the respiratory and gastrointestinal system [1]. Studies from our group and others have showed that some flavonoids have estrogenic activity [6,7,8,9,10] and are named phytoestrogens. ERs are members of the nuclear receptor superfamily and act as a ligand-activated transcription factors to regulate the expression of target genes. They are expressed in various immune cells, including macrophages [13,14] that play a critical role in many inflammatory diseases by expressing pro-inflammatory mediators, including tumor necrosis factor (TNF)-α, Interleukin (IL)-1, interleukin (IL)-6, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) [15,16]. Lipopolysaccharide (LPS) is most frequently used to study macrophage biology [17]
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