Pseudohypericin is necessary for the light-activated inhibition of prostaglandin E2 pathways by a 4 component system mimicking an Hypericum perforatum fraction

Kimberly D.P. Hammer, Matthew L. Hillwig, Jeffrey Neighbors, Young Je Sim, Marian L. Kohut, David F. Wiemer, Eve S. Wurtele, Diane F. Birt

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2354-2362
Number of pages9
JournalPhytochemistry
Volume69
Issue number12
DOIs
StatePublished - Sep 1 2008

Fingerprint

Hypericum
Hypericum perforatum
Dinoprostone
prostaglandins
Light
Anti-Inflammatory Agents
Lipopolysaccharides
Cytosolic Phospholipases A2
Cytokines
Chlorogenic Acid
Lipoxygenase
Bioassay
Quercetin
Interleukin-10
lipopolysaccharides
cytokines
Ethanol
Tumor Necrosis Factor-alpha
inflammation
Inflammation Mediators

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Plant Science
  • Horticulture

Cite this

Hammer, Kimberly D.P. ; Hillwig, Matthew L. ; Neighbors, Jeffrey ; Sim, Young Je ; Kohut, Marian L. ; Wiemer, David F. ; Wurtele, Eve S. ; Birt, Diane F. / Pseudohypericin is necessary for the light-activated inhibition of prostaglandin E2 pathways by a 4 component system mimicking an Hypericum perforatum fraction. In: Phytochemistry. 2008 ; Vol. 69, No. 12. pp. 2354-2362.
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abstract = "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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Pseudohypericin is necessary for the light-activated inhibition of prostaglandin E2 pathways by a 4 component system mimicking an Hypericum perforatum fraction. / Hammer, Kimberly D.P.; Hillwig, Matthew L.; Neighbors, Jeffrey; Sim, Young Je; Kohut, Marian L.; Wiemer, David F.; Wurtele, Eve S.; Birt, Diane F.

In: Phytochemistry, Vol. 69, No. 12, 01.09.2008, p. 2354-2362.

Research output: Contribution to journalArticle

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

AU - Sim, Young Je

AU - Kohut, Marian L.

AU - Wiemer, David F.

AU - Wurtele, Eve S.

AU - Birt, Diane F.

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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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