Anti-inflammatory guaiane-type sesquiterpenes from the fruits of Pittosporum undulatum

• Published in: Phytochemistry (Oxford) Vol. 95; pp. 308 - 314
• Main Authors: Mendes, Sofia A.C., Mansoor, Tayyab A., Rodrigues, Ana, Armas, Jácome Bruges, Ferreira, Maria-José U.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.11.2013; Elsevier
• Subjects: Animals; Anti-inflammatory activity; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Azores; Biochemistry & Molecular Biology; carcinoma; cytotoxicity; fractionation; Fruit - chemistry; fruits; Glucosides - chemistry; Glucosides - isolation & purification; Glucosides - pharmacology; Glucosides - therapeutic use; glycosides; Guaiane sesquiterpenes; indomethacin; Inflammation - chemically induced; Inflammation - drug therapy; Inhibitory Concentration 50; isomers; Life Sciences & Biomedicine; Lipopolysaccharides; macrophages; Macrophages - drug effects; Magnoliopsida - chemistry; medicine; melanoma; Mice; Molecular Structure; Nitric oxide; nuclear magnetic resonance spectroscopy; Phytotherapy; Pittosporacea; Pittosporum; Pittosporum undulatum; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant Sciences; Rosales - chemistry; Science & Technology; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; sesquiterpenoids; Traditional medicine of Azores; Anti-inflammatory activity; Pittosporum undulatum; Pittosporacea; Traditional medicine of Azores; Nitric oxide; Guaiane sesquiterpenes; GLYCOSIDES; ELUCIDATION; ESSENTIAL OILS; AZORES; CONSTITUENTS
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2013.06.019

Two unprecedented guaiane-type sesquiterpene glycosides, along with six known compounds, including two guaianes, were isolated from Pittosporum undulatum. Guaianes displayed in vitro anti-inflammatory activity comparable to that of indomethacin. •Two unprecedented guaiane glycosides, along with six known compounds, including two guaianes, were isolated.•Guaianes displayed in vitro anti-inflammatory activity comparable to that of indomethacin.•Guaianes were also assessed for their anti-proliferative activity in cancer cells. 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=18.2μM), with no cytotoxic effects (IC50⩾198μM). 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.