5′-methoxyhydnocarpin-D and pheophorbide A:: Berberis species components that potentiate berberine growth inhibition of resistant Staphylococcus aureus

A new method of bioactivity-directed fractionation, based on multidrug resistant pump (MDR) inhibition in Staphylococcus aureus, was demonstrated. This resulted in the isolation, from berberine-containing Berberis species, of two compounds that are themselves devoid of S. aureus antibacterial activity, but that form potent synergistic couples with a subinhibitory concentration of berberine. The bacterial MDR pump inhibitors were identified as the flavonolignan 2 and the porphyrin 3. Another natural flavonolignan, silybin (8) from Silybum marianum, was also shown to be a bacterial MDR pump inhibitor.