title: Two new proanthocyanidin trimers isolated from Cistus incanus L. demonstrate potent anti-inflammatory activity and selectivity to cyclooxygenase isoenzymes inhibition.
abstract: Two new proanthocyanidin trimers have been isolated from Cistus incanus herb; gallocatechin-(4α→6)-gallocatechin-(4α→8)-gallocatechin (compound 1) and epigallocatechin-3-O-gallate-(4ß→8)-epigallocatechin-3-O-gallate-(4ß→8)-gallocatechin (compound 2). The structures were determined on the basis of 1D- and 2D-NMR (HSQC, HMBC) of their peracetylated derivatives, MALDI-TOF-MS and by acid-catalysed degradation with phloroglucinol. A more abundant proanthocyanidin oligomer was also isolated, purified and its chemical constitution studied by (13)C-NMR and phloroglucinol degradation. The mean molecular weight of the polymer was estimated to be about 7 to 8 flavan-3-ol-units with a ratio of procyanidin : prodelphinidin units at 1:5, some of which are derivatised by gallic acid. Water extract and higher oligomeric proanthocyanidin fractions of C. incanus significantly inhibited TPA-induced oedema when applied topically at doses of 0.5 and 1 mg/ear in mice. Furthermore, the extracts and the pure compounds inhibited COX-1 and COX-2 activities. In addition, compound 2 exhibited an IC50 of 4.5 μM against COX-2 indicating its high selectivity towards COX-2.
authors.affiliation: a Faculty of Pharmacy & Medical Sciences, Department of Pharmaceutical Medicinal Chemistry , University of Petra , Amman , Jordan.
authors.forename: K A
authors.initials: KA
authors.lastname: Mansoor
authors.affiliation: b Faculty of Health Sciences, Department of Medical Laboratories , American University of Madaba , Madaba , Jordan.
authors.forename: K Z
authors.initials: KZ
authors.lastname: Matalka
authors.affiliation: c HerbResearch , Mattsies , Germany.
authors.forename: F S
authors.initials: FS
authors.lastname: Qa'dan
authors.affiliation: a Faculty of Pharmacy & Medical Sciences, Department of Pharmaceutical Medicinal Chemistry , University of Petra , Amman , Jordan.
authors.forename: R
authors.initials: R
authors.lastname: Awad
authors.affiliation: c HerbResearch , Mattsies , Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D029758:Cistus / Q000737:chemistry*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010936:Plant Extracts / Q000032:analysis; D044945:Proanthocyanidins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D010936:Plant Extracts; D044945:Proanthocyanidins
keywords: COX inhibitor; Cistus incanus; anti-inflammatory; phenolic; proanthocyanidins