Synergistic effect and efflux pump inhibitory activity of Ficus nitida phenolic extract with tetracycline against some pathogenic bacteria

Abstract

Antibiotic resistance by pathogenic bacteria has risen to dangerous level all over the world. The study is aimed to evaluate the potential synergistic interaction of Ficus nitida bark phenolic extract with tetracycline against some pathogenic bacterial strains. The phenolic profile of the F. nitida bark acetone extract was determined using HPLC-PDA-MS/MS and the synergistic interaction of the acetone extract with tetracycline was evaluated by checkerboard assay followed by molecular docking. Fourteen phenolic compounds were identified in the acetone extract that include quinic acid and its derivatives in addition to flavan-3-ol and procyanidin derivatives. Synergistic interaction between the acetone extract and tetracycline was investigated against Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa with fraction inhibitory concentration index (FICI) values of 0.43, 0.50, 0.38, and 0.375, respectively and the additive effect against Salmonella typhi and Klebsiella pneumonia with FICI value of 0.625 and 0.75, respectively. In silico molecular docking study of some acetone fractions, namely; 5-caffeoyl quinic acid, Catechin-O- trihydroxy phenyl rhamnoside, Cinchonain, and Equisetumpyrone indicated that these constituents exhibited synergistic effect due to their efflux pump inhibitory effect. Significant enhancement in antibacterial activity was observed against both Gram positive and Gram negative bacteria due to combination of F. nitida phenolic extract with tetracycline. Thus, can be used as new antibiotic agent in pharmaceutical and veterinary industries.

Keywords:

• Synergistic effect
• HPLC-PDA-MS
• phenolic compounds
• efflux pump inhibitors
• molecular docking

Acknowledgments

The authors thank DSR for technical and financial support. Also, the authors are thankful to Dr. Michael Wink and Dr. Mansour Sobeh (IPMB), Universität Heidelberg, Germany for collecting HPLC-MS/MS data.

Disclosure statement

The authors declare no conflict of interest currently.

Additional information

Funding

This work was funded by the Deanship of Scientific Research (DSR), University of Jeddah, Jeddah, under grant no. (UJ-40–18-DR).