Campus Units

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

Document Type


Publication Version

Accepted Manuscript

Publication Date


Journal or Book Title




First Page


Last Page





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.


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.



File Format


Published Version