Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of, Food Science and Human Nutrition, Nutritional Sciences

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

4-2012

Journal or Book Title

Phytochemistry

Volume

76

First Page

106

Last Page

116

DOI

10.1016/j.phytochem.2011.12.001

Abstract

Our previous studies found that 4 compounds, namely pseudohypericin, amentoflavone, quercetin, and chlorogenic acid in Hypericum perforatum ethanol extract synergistically inhibited lipopolysaccharide (LPS)-induced macrophage production of prostaglandin E2 (PGE2). Microarray studies led us to hypothesize that these compounds inhibited PGE2 production by activating suppressor of cytokine signaling 3 (SOCS3). In the current study we used siRNA to knockdown the expression of SOCS3 in RAW 264.7 macrophages and investigated the impact of H. perforatum extract and the 4 compounds on inflammatory mediators and cytokines. We found SOCS3 knockdown significantly compromised the inhibition of PGE2 and nitric oxide (NO) by the 4 compounds, but not by the extract. The 4 compounds, but not the extract decreased interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while both of them lowered interleukine-1β. SOCS3 knockdown further decreased IL-6 and TNF-α. Pseudohypericin was the major contributor to the PGE2 and NO inhibition in cells treated with the 4 compounds and its activity was lost with SOCS3 knockdown. Cyclooxygenase-2 (COX-2) and inducible NO synthase protein expression were not altered by the treatments, while COX-2 activity was decreased by the extract and the 4 compounds and increased by SOCS3 knockdown. In summary, we demonstrated that the 4 compounds inhibited LPS-induced PGE2 and NO through SOCS3 activation. The reduction of PGE2 can be partially attributed to COX-2 enzyme activity, which was significantly elevated with SOCS3 knockdown. At the same time, our results also suggest that constituents in H. perforatum extract were alleviating LPS-induced macrophage response through SOCS3 independent mechanisms.

Comments

This is a manuscript of an article published as Huang, Nan, Ludmila Rizshsky, Catherine C. Hauck, Basil J. Nikolau, Patricia A. Murphy, and Diane F. Birt. "The inhibition of lipopolysaccharide-induced macrophage inflammation by 4 compounds in Hypericum perforatum extract is partially dependent on the activation of SOCS3." Phytochemistry 76 (2012): 106-116. doi:10.1016/j.phytochem.2011.12.001. Posted with permission.

Copyright Owner

Elsevier Ltd.

Language

en

File Format

application/pdf

Published Version

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