Coupling biological detection to liquid chromatography: a new tool in drug discovery.

Procedures to characterize drugs that can be obtained from plant extracts or combinatorial chemistry are tedious, and they consume considerable resources (e.g., animals) and time. Thus, we have looked for a way to streamline this process. We describe here a novel system for the pre-characterization of drugs based on liquid chromatography coupled to biological detection using perifused or perfused organs. This novel system allows the on-line detection of pharmacologically active substances in hydrosoluble mixtures from vegetal extracts or combinatorial chemistry libraries. Depending on the volume of drug solution and concentration of the samples, the procedure can work through either medium pressure liquid chromatography or HPLC, and it enables the fingerprints of drugs to be assessed based on their contractile activity on combinations of different isolated tissues. As an example, we show how the system can identify active fractions from an extract of Stevia rebaudiana Bertoni, an activity that was later associated with rebaudioside N. Coupling liquid chromatography to biological detection offers a rapid way to focus attention on active products in complex samples, mostly from hydrosoluble species, helping to considerably reduce the time and cost of the pre-characterization of drugs.

Sesquiterpene lactones and other constituents of Centaurea napifolia.

Aerial parts of Centaurea napifolia furnished the sesquiterpene lactones cnicin, 4'-acetoxycnicin, melitensin, dehydromelitensin, two known esters of dehydromelitensin, lappaol and a lappaol isomer, and a 1,2-diacylated glucose.

Antinociceptive, anti-inflammatory and antipyretic effects of lapidin, a bicyclic sesquiterpene.

Lapidin, a bicyclic sesquiterpene from Ferula linkii Webb, has been evaluated for antinociceptive, anti-inflammatory, and antipyretic activities in mice and rats. Lapidin, vehicle, or the appropriate reference analgesic and anti-inflammatory compounds (acetylsalicylic acid [ASA] and indomethacin) were injected i.p. The more conspicuous effects of lapidin were: 1) a significant protective effect (17-62%; 2.5-20 mg/kg) towards writhings and stretchings induced by acetic acid in mice; 2) a significant antinociceptive effect on jumping responses in the hot-plate test (120 seconds at 15 mg/kg vs. 40 and 85 seconds in vehicle and ASA-treated mice, respectively); 3) a significant dose-dependent (5-15 mg/kg) antinociceptive effect against mechanical noxious stimuli; 4) a dose-dependent anti-inflammatory effect in the carrageenan-induced edema which, at the higher dose (20 mg/kg), was comparable (65% inhibition of paw swelling at 3 hours) to that obtained after indomethacin (10 mg/kg); and 5) a moderate antipyretic effect against yeast-induced hyperthermia. Present results demonstrate that lapidin possesses antinociceptive, anti-inflammatory, and less pronounced antipyretic effects comparable to those of classical non-steroid anti-inflammatory drugs, which make it worthy of further investigations as an antinociceptive and anti-inflammatory drug.