PubMed Health⌕ Search

Biomedical subjects

I Merfort

Publications and source records attributed to I Merfort.

29 records · Page 2Linked to original sources
PubMed1998

Study of three sesquiterpene lactones from Tithonia diversifolia on their anti-inflammatory activity using the transcription factor NF-kappa B and enzymes of the arachidonic acid pathway as targets.

In Central America leaf extracts from the Asteraceae Tithonia diversifolia are used externally for the treatment of haematomas and wounds. Therefore, the main sesquiterpene lactones (Sls) of this species growing in Costa Rica, diversifolin (1), diversifolin methyl ether (2), and tirotundin (3), were studied for their anti-inflammatory activity. We determined whether these compounds inhibit cyclooxygenase-I, phospholipase A2, or the transcription factor NF-kappa B. Here we show that these Sls do not influence the enzymes of the arachidonic acid pathway, but inhibit the activation of NF-kappa B. Thereby, the synthesis of inflammatory mediators such as cytokines and chemokines is reduced. Our results indicate that the inhibitory activity of compounds 1-3 is due to alkylation of cysteine residues, which are probably located in the DNA binding domain of NF-kappa B. The Sls were also studied for their antibacterial activity, but only Sl 1 was moderately active against Bacillus subtilis in the agar plate diffusion test.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB.

Alcoholic extracts prepared form Arnicae flos, the collective name for flowerheads from Arnica montana and A. chamissonis ssp. foliosa, are used therapeutically as anti-inflammatory remedies. The active ingredients mediating the pharmacological effect are mainly sesquiterpene lactones, such as helenalin, 11alpha,13-dihydrohelenalin, chamissonolid and their ester derivatives. While these compounds affect various cellular processes, current data do not fully explain how sesquiterpene lactones exert their anti-inflammatory effect. We show here that helenalin, and, to a much lesser degree, 11alpha,13-dihydrohelenalin and chamissonolid, inhibit activation of transcription factor NF-kappaB. This difference in efficacy, which correlates with the compounds' anti-inflammatory potency in vivo, may be explained by differences in structure and conformation. NF-kappaB, which resides in an inactive, cytoplasmic complex in unstimulated cells, is activated by phosphorylation and degradation of its inhibitory subunit, IkappaB. Helenalin inhibits NF-kappaB activation in response to four different stimuli in T-cells, B-cells and epithelial cells and abrogates kappaB-driven gene expression. This inhibition is selective, as the activity of four other transcription factors, Oct-1, TBP, Sp1 and STAT 5 was not affected. We show that inhibition is not due to a direct modification of the active NF-kappaB heterodimer. Rather, helenalin modifies the NF-kappaB/IkappaB complex, preventing the release of IkappaB. These data suggest a molecular mechanism for the anti-inflammatory effect of sesquiterpene lactones, which differs from that of other nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and acetyl salicylic acid.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Radical scavenger activity of three flavonoid metabolites studied by inhibition of chemiluminescence in human PMNs.

3,4-Dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)-propionic acid, metabolites which arise from quercetin glycosides, respectively, from flavones and probably from procyanidins by the human intestinal microflora, have been tested for their effects on oxygen radical production by human PMNs stimulated with FMLP or opsonized zymosan. Oxygen radicals were detected by luminol-augmented chemiluminescence measurements. Furthermore free radical scavenging activity of these metabolites was investigated in a cell-free system in which oxygen radicals were generated by horseradish peroxidase with H2O2 as substrate. 3,4-Dihydroxyphenylacetic acid reduced considerably chemiluminescence in PMNs in an amount which was much more pronounced than those of the other two metabolites. Concentrations of 1 mumol/l showed an inhibition by 84% with FMLP as stimulant and by 15% with opsonized zymosan, indicating that different signal transduction pathways are influenced in PMNs. Using the same conditions the unmetabolized quercetin showed an inhibition of chemiluminescence by 74% (FMLP), resp. 20% (opsonized zymosan). In the cell free system 3,4-dihydroxyphenylacetic acid suppressed much more effectively chemiluminescence than 3-hydroxyphenylacetic acid. In contrast, 3-(4-hydroxyphenyl)-propionic acid led to an increase of chemiluminescence generated in the cell-free system (FMLP and zymosan), i.e. by 30% by 25%, at the highest concentration of 4 mumol/l. In conclusion, flavonoid metabolites differ in their effects on free radical production of PMNs and their radical scavenging potencies.

Flavonoids↗
PubMed1995

Radical scavenger activity of different 3',4'-dihydroxyflavonols and 1,5-dicaffeoylquinic acid studied by inhibition of chemiluminescence.

To gain more insights into structure-activity relationships, four 3',4'-dihydroxyflavonols differing in the substitution of the A and C rings and 1,5-dicaffeolyquinic acid were evaluated for their ability to inhibit chemiluminescence of human neutrophils stimulated with opsonized zymosan or FMLP as well as in an enzymatic system with H2O2 and horseradish peroxidase. It could be shown that an additional o-dihydroxy structure in the A-ring, or a 6-methoxy group, respectively, has no significant influence, thus confirming the o-dihydroxy group of the B-ring as the most important structural feature for the radical scavenger activity. It can be supposed that the main effect of the tested flavonols is based on their inhibition of myeloperoxidase, besides inhibition of enzymes involved in activating the NADPH-oxidase, and a direct reaction with oxygen radicals. Inhibition of chemiluminescence by 1,5-dicaffeoylquinic acid was in the same order as those observed with the flavonols.

Cell-Free System↗
PubMed1994

Cytotoxicity of flavonoids and sesquiterpene lactones from Arnica species against the GLC4 and the COLO 320 cell lines.

The cytotoxicity of 21 flavonoids and 5 sesquiterpene lactones, as present in Arnica species, was studied in GLC4, a human small cell lung carcinoma cell line, and in COLO 320, a human colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. Following continuous incubation, most flavonoids showed moderate to low cytotoxicity, as compared with the reference compound cisplatin (IC50 = 1.1 microM against GLC4 and 2.9 microM against COLO 320). Their IC50 values varied from 17 to > 200 microM. The most toxic compound was the flavone jaceosidin. Of the sesquiterpene lactones tested, helenalin, possessing both the reactive alpha-methylene-gamma-lactone moiety and a reactive alpha,beta-unsubstituted cyclopentenone ring, displayed the strongest cytotoxicity. For 2 h exposure, its IC50 value was 0.44 microM against GLC4 and 1.0 microM against COLO 320. COLO 320 was more sensitive than GLC4 for many flavonoids (especially for flavones), but more resistant to the cytotoxic effect of the sesquiterpene lactones bearing an exocylic methylene group fused to the lactone function.

Adenocarcinoma↗
PubMed1994

In vivo skin penetration studies of camomile flavones.

In vivo skin penetration studies of the Camomile flavones apigenin, luteolin and apigenin 7-O-beta-glucoside were carried out with nine healthy, female volunteers. During seven hours the decline of flavonoid concentration in a saturated aqueous alcoholic solution filled in glass application chambers were repeatedly measured by spectrophotometry at fixed time periods. The maximal fluxes were calculated. From the graph of the maximal flux values as a function of time it was concluded, that the flavonoids are not only adsorbed at the skin surface, but penetrate into deeper skin layers. This is important for their topical use as antiphlogistic agents.

Administration, Topical↗
PubMed1992

New Flavonoid Glycosides from Arnicae Flos DAB 91.

Five flavonoid glycosides were identified from flowers of Arnica montana, ten from A. CHAMISSONIS subsp. FOLIOSA var. INCANA. The structures were established on the basis of acid hydrolysis and spectral data (UV, NMR, MS) as the 7-beta-glucosides of pectolinarigenin, apigenin, and chrysoeriol; luteolin 3'- O-beta-glucoside; the 3-beta-glucuronides of kaempferol, isorhamnetin, and 6-methoxykaempferol; the 3,7-di-beta-glucosides of quercetin and patuletin; the 3-beta-glucosides of betuletol and quercetagetin 6,3',4'-trimethyl ether; and the 7-[6''- O-(2-methylbutyryl)]=glucosides of luteolin and eupafolin. The latter four are new natural compounds. Differences between these two ARNICA species are discussed.

Journal Article↗
PubMed1990

Flavonoid Glycosides and Other Hydrophilic Compounds from Flowers of Heterotheca inuloides.

Ten flavonoid glycosides were identified in flowers of HETEROTHECA INULOIDES ("Mexican Arnica"). Their structures were established by spectral data (UV, (1)H-NMR, (13)C-NMR, mass) and total acid hydrolysis as kaempferol 3-beta-glucoside, 3-beta-galactoside, 3-beta-rutinoside, 3-beta-robinobioside, quercetin 3-beta-glucoside, 3-beta-galactoside, 3-beta-glucuronide, 3-beta-glucuronide-6''-methylester, 3-alpha- L-arabinoside, and 3-beta-rutinoside. Additionally, caffeic, protocatechuic, and chlorogenic acid as well as umbelliferone were found.

Journal Article↗