| The inhibition of lipopolysaccharide-induced macrophage inflammation by 4 compounds in Hypericum perforatum extract is partially dependent on the activation of SOCS3. | |
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MedLine Citation:
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PMID: 22245632 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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, siRNA was used to knockdown 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. It was found that the 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 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 the 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, it was 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, these results also suggest that constituents in H. perforatum extract were alleviating LPS-induced macrophage response through SOCS3 independent mechanisms. |
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Authors:
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Nan Huang; Ludmila Rizshsky; Catherine C Hauck; Basil J Nikolau; Patricia A Murphy; Diane F Birt |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-13 |
Journal Detail:
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Title: Phytochemistry Volume: - ISSN: 1873-3700 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0151434 Medline TA: Phytochemistry Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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The Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA 50011, United States; Interdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA 50011, United States; Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, United States. |
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