title: 3-Methyl-4,5-dihydro-oxepine, polyoxygenated seco-cyclohexenes and cyclohexenes from Uvaria flexuosa and their anti-inflammatory activity.
abstract: The phytochemical investigation of the methanolic extract of Uvaria flexuosa (Annonaceae) leaves led to the isolation of seven compounds including, 3-methyl-4,5-dihydro-oxepine (flexuvaroxepine A), four polyoxygenated seco-cyclohexene (flexuvarin A-D) and two polyoxygenated cyclohexene (flexuvarol A-B) derivatives, together with four known flavones. The structures of the isolated compounds were elucidated using different spectroscopic techniques. A plausible biogenetic route of the new compounds was discussed. The anti-inflammatory activity of the isolated compounds was evaluated by superoxide anion generation and elastase release assays. Among the tested compounds, flexuvarol B and chrysin showed the most potent anti-inflammatory effect by inhibiting superoxide anion generation and elastase release from human neutrophils in response to fMLP with IC50 2.25-5.55μM. Moreover, 5-hydroxy-6,7-dimethoxy-flavone showed selective inhibitory activity on superoxide anion generation (IC50=1.19±0.34μM).
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Hsu
authors.affiliation: Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Tung-Ying
authors.initials: TY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ying-Chi
authors.initials: YC
authors.lastname: Du
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Cairo 11566, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Shazly
authors.affiliation: Institute of Pharmaceutical Biology, Technische Universität Braunschweig, 38106 Braunschweig, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Beerhues
authors.affiliation: Faculty of Chemistry, Vinh University, 182-Le Duan, Vinh City, Nghean Province, Viet Nam.
authors.forename: Tran Dinh
authors.initials: TD
authors.lastname: Thang
authors.affiliation: Faculty of Chemistry, Vinh University, 182-Le Duan, Vinh City, Nghean Province, Viet Nam.
authors.forename: Hoang
authors.initials: H
authors.lastname: Van Luu
authors.affiliation: Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; Immunology Consortium, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; R & D Center of Chinese Herbal Medicines & New Drugs, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan. Electronic address: aaronfrc@kmu.edu.tw.
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan; School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan. Electronic address: yachwu@mail.cmu.edu.tw.
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
mesh_terms: D029061:Annonaceae / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D053138:Cyclohexenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010082:Oxepins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D031046:Uvaria / Q000737:chemistry*
chemical_list: C000610929:3-(benzoyloxymethyl)-4,5-dihydro-oxepine-4,5-diyldiacetate; C000611094:3-methyl-4,5-dihydro-oxepine; D000893:Anti-Inflammatory Agents; D053138:Cyclohexenes; D005419:Flavonoids; D010082:Oxepins; C000610931:flexuvarin; C043561:chrysin
keywords: 3-Methyl-4,5-dihydro-oxepine; Annonaceae; Anti-inflammatory; Polyoxygenated cyclohexenes; Polyoxygenated seco-cyclohexenes; Uvaria flexuosa