title: Anti-inflammatory activity in skin by biomimetic of Evodia rutaecarpa extract from traditional Chinese medicine.
abstract: BACKGROUND
  Wu-Zhu-Yu, is an extract prepared from the small berry fruit of Evodia rutaecarpa and is reported to have anti-inflammatory and anti-nociceptic activity. Methyl nicotinate (MN) is known to induce the release of PGD(2) resulting in localized erythema within 30 min after topical application to human skin.
  
  
  OBJECTIVE
  The purpose of this study was to determine if a defined biomimetic mixture of components of Evodia fruit extract inhibit inflammation in human cells and skin.
  
  
  METHODS
  In order to control the potency of the test article, we prepared a defined biomimetic mixture of synthetic and natural forms of the active components of Evodia fruit extract, containing rutaecarpine, dehydroevodiamine, and evodin. This was tested for anti-inflammatory activity in UVB-irradiated cultured cells and in the MN model of micro-inflammation in human skin.
  
  
  RESULTS
  This Evodia biomimetic mixture was a potent inhibitor of UVB-induced PGE(2) released by keratinocytes in culture. We found that MN also induces release of nitric oxide from cultured keratinocytes and microvascular endothelial cells. Twice daily application of 0.1-1% Evodia biomimetic mixture for 2 weeks significantly inhibited erythema after a MN challenge. A single application of 1% Evodia biomimetic mixture also significantly inhibited MN-induced erythema when applied at 60 min before, or within 5 min after MN exposure. The Evodia biomimetic mixture was significantly more effective at inhibiting erythema than bisabolol, the active component of chamomile.
  
  
  CONCLUSIONS
  These results demonstrate that compounds found in E. rutaecarpa (including the indole quinazoline alkaloids) have powerful anti-inflammatory activity when applied topically to human skin.
authors.affiliation: AGI Dermatics, 205 Buffalo Avenue, Freeport, NY 11520, USA. danyarosh@agiderm.com
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Yarosh
authors.forename: Jason W
authors.initials: JW
authors.lastname: Galvin
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Nay
authors.forename: Arely V
authors.initials: AV
authors.lastname: Peña
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Canning
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D032701:Biomimetics; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D004890:Erythema / Q000139:chemically induced / Q000517:prevention & control; D032086:Evodia; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D008875:Middle Aged; D009539:Nicotinic Acids; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014466:Ultraviolet Rays; D052999:Quinazolinones
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D015232:Dinoprostone; D004365:Drugs, Chinese Herbal; D005663:Furans; D006576:Heterocyclic Compounds, 4 or More Rings; D026121:Indole Alkaloids; D009539:Nicotinic Acids; D009569:Nitric Oxide; D010936:Plant Extracts; D011799:Quinazolines; C473746:evodine; C028633:dehydroevodiamine; C008473:methyl nicotinate; C028632:rutecarpine; D052999:Quinazolinones