Synergistic effect of rhein in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for a number of infections in humans that are difficult to treat, and as a result, is a substantial contributor to morbidity and mortality. In the present study, in search of natural products capable of inhibiting this multidrug-resistant bacterium, we investigated the antimicrobial activity of rhein isolated from Rheum palmatum L. (Polygonaceae) against 16 different strains of the bacterium. New antimicrobial activity was found using the paper disc diffusion method [minimal inhibitory concentrations (MICs)], MTT test and checkerboard dilution test. Against the 16 strains, the disc diffusion test was in the range of 20-29 mm and the MICs of rhein were in the range of 7.8-31.25 μg/ml. From these results we performed the checkerboard test to determine the synergism of rhein in combination with ampicillin (AM) or oxacillin (OX) against all strains. The combined activity of rhein and the two antimicrobial agents (AM and OX) against all strains resulted in a fractional inhibitory concentration index ranging from 0.28-1 and from 0.18-1, respectively. The effect of rhein with AM and OX was found to be synergistic or partially synergistic. We found that rhein reduced the MICs of AM and OX. Rhein in combination with AM or OX could lead to the development of new combinations of antibiotics against MRSA infection.