TY - JOUR
T1 - Pseudohypericin is necessary for the light-activated inhibition of prostaglandin E2 pathways by a 4 component system mimicking an Hypericum perforatum fraction
AU - Hammer, Kimberly D.P.
AU - Hillwig, Matthew L.
AU - Neighbors, Jeffrey D.
AU - Sim, Young Je
AU - Kohut, Marian L.
AU - Wiemer, David F.
AU - Wurtele, Eve S.
AU - Birt, Diane F.
N1 - Funding Information:
The authors would like to thank members of the Iowa Center for Research on Botanical Dietary Supplements. This publication was made possible by grant number 9P50AT004155-06 from the National Center for Complementary and Alternative Medicine (NCCAM) and Office of Dietary Supplements (ODS), National Institutes of Health (NIH) and P01 ES012020 from the National Institute of Environmental Health Sciences (NIEHS) and ODS, NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NCCAM, or NIH.
PY - 2008/9
Y1 - 2008/9
N2 - Hypericum perforatum (Hp) has been used medicinally to treat a variety of conditions including mild-to-moderate depression. Recently, several anti-inflammatory activities of Hp have been reported. An ethanol extract of Hp was fractionated with the guidance of an anti-inflammatory bioassay (lipopolysaccharide (LPS)-induced prostaglandin E2 production (PGE2)), and four constituents were identified. When combined together at concentrations detected in the Hp fraction to make a 4 component system, these constituents (0.1 μM chlorogenic acid (compound 1), 0.08 μM amentoflavone (compound 2), 0.07 μM quercetin (compound 3), and 0.03 μM pseudohypericin (compound 4)) explained the majority of the activity of the fraction when activated by light, but only partially explained the activity of this Hp fraction in dark conditions. One of the constituents, light-activated pseudohypericin, was necessary, but not sufficient to explain the reduction in LPS-induced PGE2 of the 4 component system. The Hp fraction and the 4 component system inhibited lipoxygenase and cytosolic phospholipase A2, two enzymes in the PGE2-mediated inflammatory response. The 4 component system inhibited the production of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), and the Hp fraction inhibited the anti-inflammatory cytokine interleukin-10 (IL-10). Thus, the Hp fraction and selected constituents from this fraction showed evidence of blocking pro-inflammatory mediators but not enhancing inflammation-suppressing mediators.
AB - Hypericum perforatum (Hp) has been used medicinally to treat a variety of conditions including mild-to-moderate depression. Recently, several anti-inflammatory activities of Hp have been reported. An ethanol extract of Hp was fractionated with the guidance of an anti-inflammatory bioassay (lipopolysaccharide (LPS)-induced prostaglandin E2 production (PGE2)), and four constituents were identified. When combined together at concentrations detected in the Hp fraction to make a 4 component system, these constituents (0.1 μM chlorogenic acid (compound 1), 0.08 μM amentoflavone (compound 2), 0.07 μM quercetin (compound 3), and 0.03 μM pseudohypericin (compound 4)) explained the majority of the activity of the fraction when activated by light, but only partially explained the activity of this Hp fraction in dark conditions. One of the constituents, light-activated pseudohypericin, was necessary, but not sufficient to explain the reduction in LPS-induced PGE2 of the 4 component system. The Hp fraction and the 4 component system inhibited lipoxygenase and cytosolic phospholipase A2, two enzymes in the PGE2-mediated inflammatory response. The 4 component system inhibited the production of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), and the Hp fraction inhibited the anti-inflammatory cytokine interleukin-10 (IL-10). Thus, the Hp fraction and selected constituents from this fraction showed evidence of blocking pro-inflammatory mediators but not enhancing inflammation-suppressing mediators.
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U2 - 10.1016/j.phytochem.2008.06.010
DO - 10.1016/j.phytochem.2008.06.010
M3 - Article
C2 - 18707743
AN - SCOPUS:51049087934
SN - 0031-9422
VL - 69
SP - 2354
EP - 2362
JO - Phytochemistry
JF - Phytochemistry
IS - 12
ER -