INTEGRATED BIOCHEMICAL AND BIOINFORMATICS EVALUATION OF PAKISTANI HONEY-DERIVED POLYPHENOLS AS POTENTIAL INHIBITORS OF ANTIMICROBIAL RESISTANCE TARGETS
Abstract
Background: Antimicrobial resistance (AMR) is a rising phenomenon worldwide, thus the need for multi-targeted biotherapies of natural origin. Although the antimicrobial activity of honey polyphenols has been demonstrated, there is a lack of understanding of the biochemical diversity of honeys from different regions.
Methods: One hundred samples of honey were collected from five different floral sources Sidr, Eucalyptus, Acacia, Beri and Clover and subjected to physicochemical analysis, spectrophotometric determination of Total Phenolic Content (TPC) and Total Flavonoid Content (TFC), antioxidant evaluation (DPPH, FRAP) and antibacterial evaluation using zone of inhibition (ZOI) method using 5 German multi-resistant pathogens S. aureus MRSA, E. coli MDR, P. acnes, P. aurelia and K. pneumonia. Molecular docking was done with β-Lactamase and DNA Gyrase B.
Results: The results showed that the polyphenolics and antioxidant activity were significantly influenced by the floral origin (p<0.001). Sidr honey exhibited highest TPC (85.25±5.64 mg GAE/100g) and TFC (35.45±2.51 mg QE/100g), while Clover showed lowest values. With floral origin there was no significant difference in the physicochemical parameters (p > 0.05). There was a positive correlation between antibacterial and polyphenolic contents, with Sidr honey showing the highest ZOI (16.64±0.65 mm) against MRSA. Strong correlations existed between TPC and ZOI (r=0.887–0.944, p<0.001). Molecular docking data showed that at any extract concentration tested, difference in free energy of binding was not significant, but favourable binding with the target proteins β-Lactamase (ΔG value of -7.91±0.87 kcal/mol) and DNA Gyrase (ΔG value of -8.18±1.10 kcal/mol).
Conclusions: Pakistani Sidr honey has an abundance of polyphenols, and it can have dual inhibitory effects on the targets that promote AMR.
Keywords
- Antimicrobial resistance; Pakistani honey; polyphenols; flavonoids; Sidr honey; molecular docking; antioxidant activity; multidrug-resistant pathogens
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