New Polyphenols Identified in Artemisiae abrotani herba Extract.

Artemisia abrotanum L. ("southernwood") belongs to the Artemisia genus and it is used in traditional medicine for the treatment of a variety of illnesses. Scarce data is available on the chemical composition of this medicinal plant, most research being focused on the quantitative and qualitative analyses of its essential oil. Our aim was to investigate the content and profile of polyphenols, flavonoids and hydroxycinnamic derivatives present in the Artemisiae abrotani herba extract. We conducted LC/MS analysis and we screened for 19 polyphenols, flavonoids and hydroxycinnamic derivatives. We determined the total content of these compounds and we screened for antioxidant activity. Most polyphenol acids, hydroxycinnamic derivatives and flavonoids were identified and quantified for the first time in this study. We found an original polyphenol distribution profile with high concentration of sinapic acid, rutin, quercetol, ferulic acid and patuletin. We measured the antioxidant activity, the ethanolic extract presenting a modest radical scavenging activity. The value of this study consists in its novelty as it adds new data on the chemical composition of A. abrotanum L. and it opens novel perspectives for medical and nutritional applications of this plant.

2-Indolylmethylenebenzofuranones as first effective inhibitors of ABCC2.

ABC-transporters play a vital role in drugs bioavailability. They prevent intracellular accumulation of toxic compounds, rendering them a major defense mechanism against harmful substances. In this large family, ABCC2 is an apical efflux pump representing about 10% of all membrane proteins in liver and small intestine, and up to 25% in colon. In these tissues, ABCC2 plays a major role in the pharmacokinetics and pharmacodynamics of endo- and xenobiotics. To gain insight in the function of this crucial protein, we have investigated and developed the first effective inhibitors of this pump. Firstly, we set up a cellular flow cytometry assay for monitoring the drug efflux carried out by ABCC2, and used it for the screening of chemical libraries derived from several chemical classes. We found that 2-indolylmethylenebenzofuranone derivatives as promising candidates. Optimization of the hits provided new compounds that inhibit ABCC2 in the micromolar range, making them the first potent ABCC2 inhibitors reported so far. Such compounds would constitute valuable tools to further investigate the role of ABCC2 in the pharmacokinetics and pharmacodynamics of drugs.

Modulators of the human ABCC2: hope from natural sources?

Human ABCC2 is an ATP-binding cassette transporter involved in the export of endobiotics and xenobiotics. It is involved in cisplatin resistance in cancer cells, particularly in ovarian cancer. The few known ABCC2 modulators are poorly efficient, so it is necessary to explore new ways to select and optimize efficient compounds ABCC2. Natural products offer an original scaffold for such a strategy and brings hope for this aim. This review covers basic knowledge about ABCC2, from distribution and topology aspects to physiological and pathological functions. It summarizes the effect of natural products as ABCC2 modulators. Certain plant metabolites act on different ABCC2 regulation levels and therefore are promising candidates to block the multidrug resistance mediated by ABCC2 in cancer cells.