title: Anti-inflammatory guaiane-type sesquiterpenes from the fruits of Pittosporum undulatum.
abstract: Two unprecedented guaiane-type sesquiterpene glycosides (undulatumosides A and B) were isolated by bioassay-guided fractionation from the MeOH extract of Pittosporum undulatum fruits, along with six known compounds, including the guaiane isomers 5-guaien-11-ol and 4-guaien-11-ol. The structures of the compounds were established as 4-guaiene-11-O-β-d-(3'-angeloxy-6'-deoxy)-glucopyranoside and 1(5)-guaiene-11-O-β-d-(3'-angeloxy-6'-deoxy)-glucopyranoside by spectroscopic methods, including 1D and 2D homo- and heteronuclear NMR experiments (COSY, HSQC, HMBC and NOESY), and HR-mass spectrometry. P. undulatum is a highly invasive weed that often outcompetes other plants, yet its fruits have become a traditional anti-inflammatory medicine in Azores. Therefore, aiming to investigate the claimed properties, the in vitro anti-inflammatory activity of guaiane-type sesquiterpenes was evaluated by analyzing their inhibitory effects on chemical mediators released by the LPS activated RAW 264.7 murine macrophages cell line. In addition, the cytotoxicity of these compounds was also evaluated in this cell line. Undulatumoside A, 5-guaien-11-ol and 4-guaien-11-ol displayed anti-inflammatory activity with IC50 values of 16.4, 8.1 and 7.2μM, respectively, comparable to that of the positive control, indomethacin (IC50=18.2 μM), with no cytotoxic effects (IC50 ≥ 198 μM). Furthermore, the same set of compounds was also assessed for anti-proliferative activity in lung large cell carcinoma COR-L23 and amelanotic melanoma C32 cells.
authors.affiliation: CITA-A, Department of Agricultural Sciences, University of Azores, Rua capitão João d'Ávila - Pico da Urze, 9700-042 Angra do Heroísmo, Azores, Portugal; iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Sofia A C
authors.initials: SA
authors.lastname: Mendes
authors.forename: Tayyab A
authors.initials: TA
authors.lastname: Mansoor
authors.forename: Ana
authors.initials: A
authors.lastname: Rodrigues
authors.forename: Jácome Bruges
authors.initials: JB
authors.lastname: Armas
authors.forename: Maria-José U
authors.initials: MJ
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001394:Azores; D005638:Fruit / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects*; D019684:Magnoliopsida / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D019685:Rosales / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D045789:Sesquiterpenes, Guaiane
chemical_list: C588387:1(5)-guaiene-11-O-(3'-angeloxy-6'-deoxy)glucopyranoside; C588386:4-guaiene-11-O-(3'-angeloxy-6'-deoxy)glucopyranoside; D000893:Anti-Inflammatory Agents; D005960:Glucosides; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane
keywords: Anti-inflammatory activity; Guaiane sesquiterpenes; Nitric oxide; Pittosporacea; Pittosporum undulatum; Traditional medicine of Azores