Studies on the antioxidative activity of phloroglucinol derivatives isolated from Hypericum species

被引:56
作者
Heilmann, J [1 ]
Winkelmann, K [1 ]
Sticher, O [1 ]
机构
[1] Swiss Fed Inst Technol, Inst Pharmaceut Sci, ETH Zurich, Dept Appl Biosci, CH-8097 Zurich, Switzerland
关键词
phloroglucinols; Hypericum; clusiaceae; antioxidative activity; reactive oxygen species;
D O I
10.1055/s-2003-38477
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
Twenty-one phloroglucinol derivatives, belonging to 8 different carbon skeletons, were tested for their ability to influence the oxidative burst of polymorphonuclear cells (PMNs) after stimulation with N-formyl-methionyl-leucyl-phenylaianine (FMLP) or opsonized zymosan (OZ). Results revealed a strong reduction of oxygen production by PMNs after stimulation with FMLP for the compounds ialibinone E (5), hyperguirione B (15) and hyperforin (21). The IC50 values obtained were 2.5 muM (5), 3.3 muM (15) and 1.8 muM (21), respectively. Slight modifications of the substituents or variation of the stereochemistry resulted in a significant loss of activity. None of the active compounds showed antioxidative activity after stimulation with OZ. The influence of compounds 5,15 and 21 on the production of oxygen radicals in an H2O2/ horse radish peroxidase system was investigated and revealed potent activity only for compound 5 (IC50 1 muM). The superoxide-scavenging properties of ialibinone E (5) and hyperguirione B (15) were additionally tested in a cytochrome c assay and only ialibinone E (5) was found to be significantly active at lower micromolar concentrations. lalibinone E (5) was not active in a xanthine oxidase assay (urate formation) in concentrations up to 100 muM and its activity is therefore not attributable to the inhibition of this enzyme. it can be assumed that the activity of compounds 5 and 15 in the different cellular and enzymatic assays, is most likely caused by different and maybe specific mechanisms and cannot be explained by a radical scavenger activity alone. None of the active phloroglucinols showed cytotoxic effects against the PMNs.
引用
收藏
页码:202 / 206
页数:5
相关论文
共 24 条
[1]   CHELATING AND FREE-RADICAL SCAVENGING MECHANISMS OF INHIBITORY-ACTION OF RUTIN AND QUERCETIN IN LIPID-PEROXIDATION [J].
AFANASEV, IB ;
DOROZHKO, AI ;
BRODSKII, AV ;
KOSTYUK, VA ;
POTAPOVITCH, AI .
BIOCHEMICAL PHARMACOLOGY, 1989, 38 (11) :1763-1769
[2]   OXIDANTS, ANTIOXIDANTS, AND THE DEGENERATIVE DISEASES OF AGING [J].
AMES, BN ;
SHIGENAGA, MK ;
HAGEN, TM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :7915-7922
[3]   NUTRITION AND HEALTH-ASPECTS OF FREE-RADICALS AND ANTIOXIDANTS [J].
ARUOMA, OI .
FOOD AND CHEMICAL TOXICOLOGY, 1994, 32 (07) :671-683
[4]  
FANTONE JC, 1982, AM J PATHOL, V107, P397
[5]  
FRIDOVICH I, 1970, J BIOL CHEM, V245, P4053
[6]   Cytosolic phospholipase A(2) and its mode of activation in human neutrophils by opsonized zymosan - Correlation between 42/44 kDa mitogen-activated protein kinase, cytosolic phospholipase A(2) and NADPH oxidase [J].
Hazan, I ;
Dana, R ;
Granot, Y ;
Levy, R .
BIOCHEMICAL JOURNAL, 1997, 326 :867-876
[7]   The requirement of both extracellular regulated kinase and p38 mitogen-activated protein kinase for stimulation of cytosolic phospholipase A2 activity by either FcγRIIA or FcγRIIIB in human neutrophils -: A possible role for Pyk2 but not for the Grb2-Sos-Shc complex [J].
Hazan-Halevy, I ;
Seger, R ;
Levy, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (17) :12416-12423
[8]   Radical scavenger activity of phenylethanoid glycosides in FMLP stimulated human polymorphonuclear leukocytes:: Structure-activity relationships [J].
Heilmann, J ;
Calis, I ;
Kirmizibekmez, H ;
Schühly, W ;
Harput, S ;
Sticher, O .
PLANTA MEDICA, 2000, 66 (08) :746-748
[9]   RADICAL SCAVENGER ACTIVITY OF DIFFERENT 3',4'-DIHYDROXYFLAVONOLS AND 1,5-DICAFFEOYLQUINIC ACID STUDIED BY INHIBITION OF CHEMILUMINESCENCE [J].
HEILMANN, J ;
MERFORT, I ;
WEISS, M .
PLANTA MEDICA, 1995, 61 (05) :435-438
[10]   EFFECTS OF FLAVONOIDS ON THE RELEASE OF REACTIVE OXYGEN SPECIES BY STIMULATED HUMAN NEUTROPHILS - MULTIVARIATE-ANALYSIS OF STRUCTURE-ACTIVITY-RELATIONSHIPS (SAR) [J].
LIMASSET, B ;
LEDOUCEN, C ;
DORE, JC ;
OJASOO, T ;
DAMON, M ;
DEPAULET, AC .
BIOCHEMICAL PHARMACOLOGY, 1993, 46 (07) :1257-1271