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

Abstract

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.

Effects of Japanese traditional herbal medicines (Kampo) on growth and virulence properties ofPorphyromonas gingivalisand viability of oral epithelial cells

“…The above results are in agreement with previous studies that showed that an anthraquinone-rich extract of another species of rhubarb (Rheum undulatum) exhibited antibacterial activity towards the cariogenic bacterium Streptococcus mutans (Song et al, 2006;Kim et al, 2011). Moreover, synergistic effects of anthraquinones (emodin, rhein) in combination with antibiotics (ampicillin, oxacillin) have been reported for methicillin-resistant Staphylococcus aureus (Joung et al, 2012;Lee et al, 2010). Although we did not investigate the action-mode of rhubarbcontaining Kampos and rhubarb-derived anthroquinones, previous studies suggest that they may act by causing damage to the bacterial cell membrane (Alves et al, 2004) and interfering with DNA replication and transcription (Lu et al, 2011).…”

Potentiation of the in vitro Antistaphylococcal Effect of Oxacillin and Tetracycline by the Anti-Inflammatory Drug Diacetyl Rhein

“…Our positive results can also be supported by the fact that the ΣFICs of both combinations observed in this study reached values of ≤0.8 for 84% of all strains tested, which could be assessed as a strong additive effect. This finding is consistent with the results of a previous study demonstrating significantly increased the antibacterial activity of ampicillin and oxacillin enhanced by rhein (active metabolite of diacetyl rhein) against various MRSA clinical isolates as well as MRSA and MSSA standard strains [18]. According to our best knowledge, this is the first report on the synergistic antibacterial effect of diacetyl rhein with oxacillin and the additive effect with tetracycline against S. aureus including its ERSA, MRSA and tetracycline-resistant (TRSA) strains.…”

“…Because of the closely related structures of diacetyl rhein and rhein and their comparable pharmacological actions [13,16], both have a marked antibacterial effect and potentiate the activity of β-lactams [18,19]; it is also likely that their modes of action could possibly be similar. Since the application of multidrug resistance pump inhibitors INF 271 and MC 207110 has previously been reported to strongly potentiate the antibacterial activity of rhein against the resistance mechanisms of S. aureus by disabling their multidrug resistance pump activity [23], this action can also be expected for diacetyl rhein.…”

“…Despite the existence of our previous in vitro study describing promising growth-inhibitory effects of diacetyl rhein against various drug-resistant staphylococcal strains [17] and recently reported synergistic antistaphylococcal effects of its active metabolite rhein with ampicillin and oxacillin [18], the potential combinatory antimicrobial effect of diacetyl rhein with existing antibiotics remains still unexplored. Therefore, we decided to screen the growth-inhibitory effect of diacetyl rhein in combination with representatives of 8 major antibiotic classes, namely aminoglycosides (streptomycin), β-lactams (cefamandole, oxacillin, penicillin G), glycopeptides (vancomycin), lincosamides (lincomycin), macrolides (erythromycin), quinolones (ciprofloxacin), sulfonamides (sulfanilamide) and tetracyclines (oxytetracycline, tetracycline), against 3 standard strains of S. aureus .…”

Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review

“…The combination activities as such against S. aureus remain to be investigated. Indeed, there have been many studies showing the potent antibacterial action of other natural compounds against S. aureus such as thymoquinone [78], rhein [79], emodin [80], silibinin [81], osthol [82], tannic acid [83], and epigallocatechin gallate [84]. These findings warrant the potential use of abovementioned compounds in combination with curcumin against S. aureus .…”