title: Anti-inflammatory activity of parthenolide-depleted Feverfew (Tanacetum parthenium).
abstract: Extracts of Tanacetum parthenium (L.) Sch. Bip., a plant known under the common name "Feverfew", contains the sesquiterpene lactone parthenolide, a potent skin sensitizer. To eliminate the risk of skin sensitization from Feverfew, we developed a parthenolide-depleted extract of Feverfew (PD-Feverfew) and determined its effectiveness as an anti-inflammatory agent. We confirmed that PD-Feverfew was sufficiently depleted of parthenolide since PD-Feverfew did not inhibit TNF-alpha induced-NF-kappaB activity unlike parthenolide containing whole Feverfew. PD-Feverfew directly inhibited the activity of pro-inflammatory enzymes 5-lipoxygenase, phosphodiesterase-3 and phosphodiesterase-4. PD-Feverfew inhibited the release of pro-inflammatory mediators nitric oxide, PGE(2) and TNF-alpha from macrophages and TNF-alpha, IL-2, IFN-gamma and IL-4 from human peripheral blood mononuclear cells. Additionally, PD-Feverfew inhibited TPA-induced release of PGE(2) from human skin equivalents. In vivo, PD-Feverfew inhibited oxazolone-induced dermatitis, and was more potent than whole Feverfew in reducing TPA-induced dermatitis. Finally the efficacy of PD-Feverfew was confirmed clinically by a reduction in erythema in a methyl nicotinate-induced vasodilation model. In conclusion, our results indicate that PD-Feverfew extracts have potent anti-inflammatory activity suggesting that this botanical would be efficacious in relieving inflammation without inducing immune sensitization.
authors.affiliation: Preclinical Pharmacology, Johnson and Johnson Skin Research Center, CPPW, a unit of Johnson & Johnson Consumer Companies, Inc., Skillman, NJ 08558, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sur
authors.forename: K
authors.initials: K
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Liebel
authors.forename: P
authors.initials: P
authors.lastname: Lyte
authors.forename: S
authors.initials: S
authors.lastname: Shapiro
authors.forename: M
authors.initials: M
authors.lastname: Southall
mesh_terms: D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D003872:Dermatitis / Q000188:drug therapy / Q000503:physiopathology; D004890:Erythema / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D010936:Plant Extracts / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000633:toxicity; D020903:Tanacetum parthenium / Q000737:chemistry*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D010936:Plant Extracts; D012717:Sesquiterpenes; C002669:parthenolide