title: Inhibitory effects of constituents of an endophytic fungus Hypoxylon investiens on nitric oxide and interleukin-6 production in RAW264.7 macrophages.
abstract: Three new compounds, hypoxyloamide (1), 8-methoxynaphthalene-1,7-diol (2), and hypoxylonol (3), together with seven compounds isolated from nature for the first time, investiamide (4), hypoxypropanamide (5), hypoxylonol A (6), investienol (7), 2-heptylfuran (8), (3S)-5-methyl-8-O-methylmellein (9), (4R)-O-methylsclerone (10), along with 19 known compounds, 11-29, were isolated from the culture broth of Hypoxylon investiens BCRC 10F0115, a fungal endophyte residing in the stems of an endemic Formosan plant Litsea akoensis var. chitouchiaoensis. The structures of the new compounds were established by spectroscopic methods, including UV, IR, HR-ESI-MS, and extensive 1D- and 2D-NMR techniques. Of these isolates, 2, 8-methoxynaphthalen-1-ol (15), and 1,8-dimethoxynaphthalene (16) showed nitric oxide (NO) inhibitory activity with IC50 values of 11.8±0.9, 17.8±1.1, and 13.3±0.5 μM, respectively, stronger than the positive control quercetin (IC50 36.8±1.3 μM). Compounds 2, 15, and 16 also showed interleukin-6 (IL-6) inhibitory activity with IC50 values of 9.2±1.7, 18.0±0.6, and 2.0±0.1 μM, stronger than the positive control quercetin (IC50 31.3±1.6 μM). To the best of our knowledge, this is the first report on guaiane sesquiterpene metabolites, 3, 6, and 7, from the genus Hypoxylon.
authors.affiliation: Graduate Institute of Natural Products (GINP), College of Pharmacy, Kaohsiung Medical University (KMU), Kaohsiung 807, Taiwan, ROC, (phone: +886-7-3121101 (ext 2191)).
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Chang
authors.forename: Hsun-Shuo
authors.initials: HS
authors.lastname: Chang
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Cheng
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Liu
authors.forename: Sung-Yuan
authors.initials: SY
authors.lastname: Hsieh
authors.forename: Gwo-Fang
authors.initials: GF
authors.lastname: Yuan
authors.forename: Ih-Sheng
authors.initials: IS
authors.lastname: Chen
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D060026:Endophytes / Q000737:chemistry*; D015850:Interleukin-6 / Q000096:biosynthesis*; D032862:Litsea / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis*; D018547:Plant Stems / Q000382:microbiology; D045789:Sesquiterpenes, Guaiane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013098:Xylariales / Q000737:chemistry*
chemical_list: D015850:Interleukin-6; D045789:Sesquiterpenes, Guaiane; D009569:Nitric Oxide
keywords: Hypoxylon investiens; Interleukin-6 inhibitory activity; Metabolites; Nitric oxide inhibitory activity