Synergism of prenylflavonoids from Morus alba root bark against clinical MRSA isolates.
Phytomedicine
; 39: 93-99, 2018 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-29433688
ABSTRACT
BACKGROUND:
Clinical methicillin-resistant Staphylococcus aureus (MRSA) is a thorny problem in current anti-infective therapeutics and a challenge of new drug development. Plant prenylflavonoids possess anti-MRSA activity, but few of the prenylflavonoids have been reported the synergistic anti-MRSA effect when they are used in combination with conventional antibacterial agents.PURPOSE:
This study deals with anti-MRSA activity of four prenylflavonoids from the root bark of Morus alba and their synergism with 11 conventional antibacterial agents.METHODS:
Chromatographic methods and spectral analysis were used to isolate and identify the prenylflavonoids. The antibacterial activity and synergism were assessed by the broth microdilution method, checkerboard dilution test, and time-kill curve assay, respectively.RESULTS:
Four prenylflavonoids, i.e., cyclocommunol (Cy, 1), morusinol (Ml, 2), morusin (Mi, 3) and kuwanon E (Ku, 4), were isolated from Morus alba bark ethanol extract. Compounds 1, 3 and 4 showed high antimicrobial activity on both methicillin-susceptible S. aureus (MSSA) and MRSA strains with MICs/MBCs at 4-16/32-64 and 4-32/16-128⯵g/ml, respectively. Ml (2) was not active. Compound 2 showed synergy with amikacin (AK) and streptomycin (SM) against all the ten MRSA isolates. Ml (2) and Ku (4) also showed synergy with ciprofloxacin (CI), etimicin (EM) and vancomycin (VA) against 7-9 isolates. The fractional inhibitory concentration indices (FICIs) ranged 0.09-1.00 and the dose reduction indices (DRIs) of these antibacterial agents ranged 2-128. Cy (1) and Mi (3) showed synergy with the tested antibacterial agents against only 1-3 MRSA isolates except VA. Furthermore, the MRSA resistance could be reversed in the combinations of AK with Cy, Ml, Mi and Ku; EM with Mi and Ku; and SM with Ml by the criteria of MIC interpretive standards for Staphylococcus spp. of CLSI. All the combinations showed only indifference in the 1â¯×â¯MIC time-killing experiments. The prenylated substitutions play an important role in the activity of the compounds used alone and combined with the tested antibacterials.CONCLUSIONS:
The study revealed for the first time the anti-MRSA synergism of prenylflavonoids 1-4 with eleven antibacterial agents and the reversal of MRSA resistance to aminoglycosides, especially amikacin. The results might be valuable for the development of new antibacterial drugs and synergists against MRSA infection.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Flavonoides
/
Morus
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Staphylococcus aureus Resistente a Meticilina
/
Antibacterianos
Tipo de estudio:
Guideline
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Phytomedicine
Asunto de la revista:
TERAPIAS COMPLEMENTARES
Año:
2018
Tipo del documento:
Article