title: Anti-inflammatory coumarins with short- and long-chain hydrophobic groups from roots of Angelica dahurica cv. Hangbaizhi.
abstract: The (1)H NMR-guided fractionation of a cyclohexane soluble portion of the 75% ethanolic extract of the roots of Angelica dahurica cv. Hangbaizhi led to the isolation of two coumarins, namely, 5-(3"-hydroxy-3"-methylbutyl)-8-hydroxyfuranocoumarin, and isobyakangelicin hydrate-3"-ethyl ether, and ten coumarins with short- or long-chain hydrophobic groups, namely, andafocoumarins A-J. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of the C-2" secondary alcohols in ten of these compounds were deduced via the circular dichroism data of the in situ formed [Rh2(OCOCF3)4] complex, and oxidation reactions were utilized to determine location of the double bonds in the lipid chain of andafocoumarins H and I, respectively. The long-chain hydrophobic group of andafocoumarin J was determined by the method of chemical degradation and GC-MS analysis. It was the first time that coumarins with short- or long-chain hydrophobic groups in this plant had been comprehensively investigated. All isolates were assayed for their inhibitory effect against nitric oxide (NO) production in a lipopolysaccharide (LPS)-activated RAW264.7 macrophage cell line, among which andafocoumarins A and B exhibited a potent inhibition on LPS-activated NO production with IC50 values of 19.7 and 13.9 μM, respectively, indicating their stronger inhibitory activity than l-N(6)-(1-iminoethyl)-lysine (IC50=23.7 μM), a selective inhibitor of inducible nitric oxide synthase.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, PR China.
authors.forename: Xiu-Wen
authors.initials: XW
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, PR China.
authors.forename: Gai-Gai
authors.initials: GG
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs (Peking University), Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Peking University, Beijing 100191, PR China. Electronic address: xwyang@bjmu.edu.cn.
authors.forename: Xiu-Wei
authors.initials: XW
authors.lastname: Yang
mesh_terms: D029969:Angelica / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D018517:Plant Roots / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D008070:Lipopolysaccharides; C090663:N(6)-(1-iminoethyl)lysine; D009569:Nitric Oxide; D008239:Lysine
keywords: Angelica dahurica cv. Hangbaizhi; Apiaceae; Coumarins with long-chain hydrophobic groups; Inhibition; NO; Rh(2)(OCOCF(3))(4)-induced CD experiments