Synergy in a medicinal plant: Antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor

Multidrug resistance pumps (MDRs) protect microbial cells from both synthetic and natural antimicrobials. Amphipathic cations are preferred substrates of MDRs. Berberine alkaloids, which are cationic antimicrobials produced by a variety of plants, are readily extruded by MDRs. Several Berberis medicinal plants producing berberine were found also to synthesize an inhibitor of the NorA MDR pump of a human pathogen Staphylococcus aureus. The inhibitor was identified as 5′-methoxyhydnocarpin (5′-MHC), previously reported as a minor component of chaulmoogra oil, a traditional therapy for leprosy. 5′-MHC is an amphipathic weak acid and is distinctly different from the cationic substrates of NorA. 5′-MHC had no antimicrobial activity alone but strongly potentiated the action of berberine and other NorA substrates against S. aureus. MDR-dependent efflux of ethidium bromide and berberine from S. aureus cells was completely inhibited by 5′-MHC. The level of accumulation of berberine in the cells was increased strongly in the presence of 5′-MHC, indicating that this plant compound effectively disabled the bacterial resistance mechanism against the berberine antimicrobial.

Cation-pi interactions in aromatics of biological and medicinal interest: electrostatic potential surfaces as a useful qualitative guide.

The cation-pi interaction is an important, general force for molecular recognition in biological receptors. Through the sidechains of aromatic amino acids, novel binding sites for cationic ligands such as acetylcholine can be constructed. We report here a number of calculations on prototypical cation-pi systems, emphasizing structures of relevance to biological receptors and prototypical heterocycles of the type often of importance in medicinal chemistry. Trends in the data can be rationalized using a relatively simple model that emphasizes the electrostatic component of the cation-pi interaction. In particular, plots of the electrostatic potential surfaces of the relevant aromatics provide useful guidelines for predicting cation-pi interactions in new systems.

Traditional knowledge of medicinal plants in the Serra de Mariola Natural Park, South-eastern Spain

The present study aims to inventory and analyse the ethnobotanical knowledge about medicinal plants in the Serra de Mariola Natural Park. In respect to traditional uses, 93 species reported by local informants were therapeutic, 27 food, 4 natural dyes and 13 handcrafts. We developed a methodology that allowed the location of individuals or vegetation communities with a specific popular use. We prepared a geographic information system (GIS) that included gender, family, scientific nomenclature and common names in Spanish and Catalan for each species. We also made a classification of 39 medicinal uses from ATC (Anatomical, Therapeutic, Chemical classification system). Labiatae (n=19), Compositae (n=9) and Leguminosae (n=6) were the families most represented among the plants used to different purposes in humans. Species with the most elevated cultural importance index (CI) values were Thymus vulgaris (CI=1.431), Rosmarinus officinalis (CI=1.415), Eryngium campestre (CI=1.325), Verbascum sinuatum (CI=1.106) and Sideritis angustifolia (CI=1.041). Thus, the collected plants with more therapeutic uses were: Lippia triphylla (12), Thymus vulgaris and Allium roseum (9) and Erygium campestre (8). The most repeated ATC uses were: G04 (urological use), D03 (treatment of wounds and ulcers) and R02 (throat diseases). These results were in a geographic map where each point represented an individual of any species. A database was created with the corresponding therapeutic uses. This application is useful for the identification of individuals and the selection of species for specific medicinal properties. In the end, knowledge of these useful plants may be interesting to revive the local economy and in some cases promote their cultivation.