Inhibitory effects of the lichen metabolite lobaric acid on arachidonate metabolism in vitro.

An extract containing phenolic constituents of the lichen Stereocaulon alpinum was shown to exhibit potent in vitro inhibitory effects on arachidonate 5-lipoxygenase from porcine leucocytes. The active component has been identified as the orcinol depsidone lobaric acid (1), which shows dose-dependent inhibitory effects on the enzyme, with an IC(50) value of 7.3 µM. Lobaric acid exhibits approximately 4-fold in vitro selectivity for 5-lipoxygenase as compared to cyclooxygenase.

In vitro inhibition of cyclooxygenase and 5-lipoxygenase by alkamides from Echinacea and Achillea species.

Polyunsaturated alkamides isolated from Achillea species, Echinacea angustifolia DC., Anacyclus pyrethrum (L.) Link, and Aaronsohnia pubescens (Desf.) Bremer & Humphries, (Compositae) were shown to possess inhibitory activity in in vitro cyclooxygenase (sheep seminal microsomes) and 5-lipoxygenase (porcine leukocytes) assays. Activity appeared to depend on the particular structure of the alkamides.

Anti-inflammatory active polyacetylenes from Bidens campylotheca.

The n-hexane extract of Bidens campylotheca Schultz Bip. ssp campylotheca (Compositae) showed significant in vitro inhibition of cyclooxygenase (CO) and 5-lipoxygenase (5-LO). Five polyacetylenes, heptadeca-2E,8E,10E,16-tetraene-4,6-diyne (1), heptadeca-2E,8Z,10E,16-tetraene-4,6-diyne (2), heptadeca-2E,8E,16-triene-4,6-diyne-10-ol (3), safynol (5) and, as a new compound, safynol-2-O-isobutyrate (4) could be isolated and their structures elucidated mainly by UV, MS, NMR, and COSY-NMR. The isolated compounds exhibited a significant inhibitory effect on cyclooxygenase and 5-lipoxygenase.

In vitro inhibition of 5-lipoxygenase by protolichesterinic acid from Cetraria islandica.

The aliphatic α-methylene-γ-lactone (+)-protolichesterinic acid (1), isolated from Cetraria islandica, has been shown to exhibit inhibitory effects on the enzyme 5-lipoxygenase in an in vitro assay in which porcine leucocytes are used as a source of the enzyme system. The isomeric compounds (+)-lichesterinic acid (2) and (-)-lichesterinic acid (4), prepared from (+)-protolichesterinic- and (-)-allo-protolichesterinic acids, respectively, exhibited anti-5-lipoxygenase activity of the same order of magnitude. (+)-Methyl lichesterinate (3) was, however, inactive. It was shown that despite its lipophilic nature, protolichesterinic acid is extractable into an aqueous medium, the concentration being dependent on the length of extraction.

[Anti-inflammatory activity of sabal fruit extracts prepared with supercritical carbon dioxide. In vitro antagonists of cyclooxygenase and 5-lipoxygenase metabolism]. / Antiphlogistische Wirkung eines mit hyperkritischem Kohlendioxid gewonnenen Sabalfrucht-Extraktes. In-vitro-Hemmung des Cyclooxygenase- und 5-Lipoxygenase-Metabolismus.

The extract SG 291 (Talso, Talso uno) from the fruits of Sabal serrulata (syn.: Serenoa repens) prepared by supercritical fluid extraction with carbon dioxide is used for the treatment of benign prostatic hyperplasia (BPH) and non bacterial prostatitis. In the present work, the Sabal extract SG 291 was analyzed by gas chromatography and investigated for its inhibitory influence on the biosynthesis of inflammatory arachidonic acid metabolites. The extract SG 291 was found in vitro to be a dual inhibitor of the cyclooxygenase (IC50-value: 28.1 micrograms/ml) and 5-lipoxygenase pathway (IC50-value: 18.0 micrograms/ml). By alkaline hydrolysis, ether extraction and preparative thin layer chromatography the extract SG 291 was separated in three fractions containing acid lipophilic compounds (A), fatty alcohols (B) and sterols (C) as main components. Fraction A inhibited the biosynthesis of cyclooxygenase (CO) and 5-lipoxygenase (5-LO) metabolites in the same intensity as the native extract SG 291, while the fractions B, C and beta-sitosterol showed no inhibitory effect on both enzymes of the arachidonic acid pathways. Therefore, the CO and 5-LO inhibiting principle of Sabal serrulata extract SG 291 must be localized in the acidic lipophilic fraction (SLF). The CO and 5-LO inhibitory effects may give an explanation for the in vivo observed antiphlogistic and antiedematous activity of the lipophilic Sabal serrulata extract SG 291.

Comparative pharmacological investigations of Allium ursinum and Allium sativum.

Extracts of wild garlic (Allium ursinum) and garlic (A. sativum) with defined chemical compositions were investigated for their in vitro inhibitory potential on 5-lipoxygenase (LO), cyclooxygenase (CO), thrombocyte aggregation (TA), and angiotensin I-converting enzyme (ACE). The inhibition rates as IC50 values of both extracts for 5-LO, CO, and TA showed a good correlation with the %-content of the major S-containing compounds (thiosulfinates and ajoenes) of the various extracts. In the 5-LO and CO test the garlic extracts are slightly superior to the wild garlic extracts whereas, in the TA test, no differences could be found. In the ACE test the water extract of the leaves of wild garlic containing glutamyl-peptides showed the highest inhibitory activity followed by that of the garlic leaf and the bulbs of both drugs. The comparative studies underline the usefulness of wild garlic as a substitute of garlic.

Anti-inflammatory effects of onions: inhibition of chemotaxis of human polymorphonuclear leukocytes by thiosulfinates and cepaenes.

Seven different synthetic thiosulfinates, and cepaene- and/or thiosulfinate-rich onion extracts were found to inhibit in vitro the chemotaxis of human granulocytes induced by formyl-methionine-leucine-phenylalanine in a dose-dependent manner and at a concentration range of 0.1-100 microM. Diphenylthiosulfinate showed the highest activity and was found to be more active than prednisolone. The anti-inflammatory properties of onion extracts are related, at least in part, to the inhibition of inflammatory cell influx by thiosulfinates and cepaenes.

Antiasthmatic effects of onions: inhibition of 5-lipoxygenase and cyclooxygenase in vitro by thiosulfinates and "Cepaenes".

Nine thiosulfinates (TS) and four "Cepaenes" (CS) isolated from onions and/or synthetized by us showed dose dependent (0.25 to 100 microM) marked inhibitory effects on both cyclooxygenase (CA, tested on sheep seminal vesicle microsomes) and 5-lipoxygenase activity (LO, tested on porcine leukocytes). The following rank order of activity was observed: saturated aliphatic TS less than aromatic TS approximately alpha, beta-unsaturated TS less than CS. CS inhibited both CA and LO by more than 75% at 10 and 1 microM concentrations respectively. Most likely, these in vitro effects are responsible for antiinflammatory and antiasthmatic properties of onion extracts observed in vivo, at least in part.