title: Anti-Inflammatory Chemical Profiling of the Australian Rainforest Tree Alphitonia petriei (Rhamnaceae).
abstract: Chronic inflammation is an important pathological condition in many human diseases, and due to the side effects of the currently used non-steroidal anti-inflammatory drugs, discovery of novel anti-inflammatory drugs is of general interest. Anti-inflammatory activity guided compound isolation from the plantAlphitonia petrieiled to the isolation of the known plant sterols emmolic acid (1), alphitolic acid (2),trans-andcis-coumaroyl esters of alphitolic acid (3and4) and betulinic acid (5). A detailed spectroscopic analysis led to the structure elucidation of the alphitolic acid derivatives (1-5), and the semi-synthetic emmolic acid acetate (6). When tested in LPS (Lipopolysaccharides) + IFN-γ (Interferon gamma) activated RAW 264.7 macrophages, all compounds except (1) exhibited potent anti-inflammatory activity (IC50values as low as 1.7 μM) in terms of downregulation of NO and TNF-α production, but also demonstrated some considerable cytotoxicity.
authors.affiliation: School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. r.raju@westernsydney.edu.au.|Molecular Medicine Research Group, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. r.raju@westernsydney.edu.au.
authors.forename: Ritesh
authors.initials: R
authors.lastname: Raju
authors.affiliation: School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. d.gunawardena@westernsydney.edu.au.
authors.forename: Dhanushka
authors.initials: D
authors.lastname: Gunawardena
authors.affiliation: School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.ahktar@uws.edu.au.
authors.forename: Most Afia
authors.initials: MA
authors.lastname: Ahktar
authors.affiliation: National Institute of Complementary Medicine (NICM), Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. mitchell.low@westernsydney.edu.au.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Low
authors.affiliation: Ecobiotics Limited, 7 Penda Street, Yungaburra, QLD 4884, Australia. Paul.Reddell@ecobiotics.com.au.
authors.forename: Paul
authors.initials: P
authors.lastname: Reddell
authors.affiliation: School of Medicine, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. g.muench@westernsydney.edu.au.|Molecular Medicine Research Group, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. g.muench@westernsydney.edu.au.
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D001315:Australia; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D065947:Rainforest; D027823:Rhamnaceae / Q000737:chemistry*; D014197:Trees
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D016207:Cytokines; D010936:Plant Extracts; D009569:Nitric Oxide
keywords: TNF-α; alphitolic acid; anti-inflammatory; natural products; nitric oxide