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A Synergistic effect of artocarpanone from Artocarpus heterophyllus Lam. (Moraceae) on the antibacterial activity of some antibiotics and their effect on membrane permeability

Abdi Wira Septama, Jianbo Xiao, Pharkphoom Panichayupakaranant.


Aim/backgrounds: Artocarpanone isolated from Artocarpus heterophyllus Lam. (Moraceae) possesses antibacterial activity. The present study investigated any interaction between artocarpanone and some antibiotics including tetracycline, ampicillin and norfloxacin against Methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Escherichia coli, as well as determining any disruptive effect on bacterial membranes.
Materials and methods: A broth microdilution method was used for the susceptibility assay. Any synergistic effect was determined using a checerboard method, and any membrane disruption effect was investigated using a bacteriolysis assay and a measurement of the released 260 nm absorbing materials.
Results and discussion: Artocarpanone exhibited weak antibacterial activities against MRSA and P. aeruginosa with MIC values of 125 and 500 µg/mL, respectively. However, it showed the strong antibacterial activity against E. coli (7.8 µg/mL). The interaction between artcarpanone with all tested antibiotics against P. aeruginosa and E. coli only revealed indifference and additive effects (FICI values of 0.75-1.25). The interaction between artocarpanone (31.2 µg/mL) and norfloxacin (3.9 µg/mL) exhibited a synergistic antibacterial activity against MRSA, with a fractional inhibitory concentration index (FICI) of 0.28, while the interaction between artocarpanone and tetracycline, and ampicillin showed an additive effect, with an FICI value of 0.5. A time kill assay also indicated that artocarpanone had a synergistic effect on the antibacterial activity of norfloxacin. In addition, a combination of artocarpanone and norfloxacin altered the membrane permeability of MRSA. Conclusion: These findings suggested that artocarpanone may be considered as an adjuvant to enhance the antibacterial activity of norfloxacin against MRSA.

Key words: artocarpanone; synergistic; norfloxacin; tetracycline; ampicillin

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