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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• 作者：Nan Huang^a ; ^b ; ^c ; ^{huangnan@iastate.edu} ; Ludmila Rizshsky^a ; ^d ; ^{ludmilar@iastate.edu} ; Catherine C. Hauck^a ; ^c ; ^{cchauck@iastate.edu} ; Basil J. Nikolau^a ; ^d ; ^{dimmas@iastate.edu} ; Patricia A. Murphy^a ; ^c ; ^{pmurphy@iastate.edu} ; Diane F. Birt^a ; ^b ; ^c ; ^{dbirt@iastate.edu}
• 关键词：Hypericum perforatum ; Guttiferae ; Inflammation ; Lipopolysaccharide ; Macrophage ; Nitric oxide ; Prostaglandin E2 ; St. John&rsquo ; s wort ; Suppressor of cytokine signaling 3
• 刊名：Phytochemistry
• 出版年：2012
• 期刊代码：85_00319422
• 类别：ch
• 出版时间：April, 2012
• 卷：76
• 期：Complete
• 页码：106-116
• 文件大小：2033 K

摘要

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-伪 (TNF-伪), while both lowered interleukine-1尾. SOCS3 knockdown further decreased IL-6 and TNF-伪. 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.