Prenylated phenolics from Morus alba against MRSA infections as a strategy for wound healing

Area of Science:

• Pharmacology and Natural Products Chemistry
• Microbiology and Infectious Diseases
• Dermatology and Wound Healing

Background:

• Antimicrobial resistance (AMR) poses a significant global health threat, with increasing multidrug-resistant bacteria rendering common antibiotics ineffective for skin infections.
• The urgent need for novel therapeutic strategies necessitates the exploration of alternative antibacterial agents, particularly for wound healing applications.

Purpose of the Study:

• To investigate the antibacterial potential of prenylated phenolics isolated from *Morus alba* root bark against *Staphylococcus aureus*, including methicillin-resistant strains (MRSA).
• To evaluate the synergistic effects of these compounds when combined with conventional antibiotics.
• To elucidate the mechanisms underlying their antibacterial activity, including membrane disruption and efflux pump inhibition.

Main Methods:

• Isolation and characterization of prenylated phenolics from *Morus alba* root bark.
• Determination of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) using microdilution and agar methods.
• Synergy assessment via checkerboard titration; evaluation of membrane-disrupting activity and efflux pump inhibition.

Main Results:

• Prenylated phenolics exhibited significant antibacterial activity against MRSA at low concentrations (MIC 2–8 μg/ml).
• Combinations of active phenolics with kanamycin, oxacillin, and ciprofloxacin demonstrated synergistic effects, reducing antibiotic MICs.
• Kuwanon C, E, T, morusin, and albafuran C showed synergy with oxacillin and/or kanamycin; prenylated phenolics disrupted bacterial membranes and kuwanon C inhibited efflux pumps.
• These compounds showed minimal cytotoxicity to human keratinocytes (HaCaT) at effective concentrations.

Conclusions:

• Prenylated phenolics from *Morus alba* possess potent antibacterial properties against MRSA and can enhance the efficacy of existing antibiotics.
• The observed membrane-disrupting activity and efflux pump inhibition contribute to their complex antibacterial mechanism.
• These natural compounds represent promising candidates for developing novel therapeutic strategies for MRSA-infected wounds, warranting further investigation.