Bioactive compounds from fermented Vernonia amygdalina leaf
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Date
2024
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In-silico Pharmacology
Abstract
Antibiotic resistance microorganisms (ARMs), particularly gram-negative bacteria, pose a global health threat. The effects
of fermentation on phytochemicals are numerous, and exploring this potential is the focus of drug development. The study
investigated the role of fermentation in modifying V. amygdalina leaf secondary metabolites as an effective antibiotic
against Escherichia. coli, Bacillus subtilis and Salmonella typhi. This work showed that fermentation increased the con
tent of lycopene, flavonoid and carotenoid compounds but decreased chlorophyll, soluble protein and phenol. Pearson’s
correlation heatmap showed a strong correlation between microbial activities and secondary metabolic changes. The
methanolic extract of fermented V. amygdalina leaf pulp (at day 9) showed significant antioxidant and anti-inflammatory
activities. The GCMS and FTIR results showed unique compounds and structural modifications at different intervals of
the fermentation period. In-vitro and in-silico analyses showed that fermentation did not alter the inhibition rate against
B. subtilis; however, E. coli and S. typhi were significantly inhibited by fermented V. amygdalina pulp extracts. In-silico
analyses showed that 4,6-Cholestadien-3β-ol– a compound present only on the ninth day of fermentation–was responsible
for the inhibition of the gram-negative bacteria via the substitution of multiple non-ionic interactions of some key cata
lytic site residues with non-ionic types, thereby denying ionisation and salt-bridge properties that porins explore to resist
antibiotics; and higher binding affinity to OmpC and OmpF than ampicillin. Therefore, this steroid-derived compound may
open a new pipeline for developing ion-independent multi-target antibiotics against broad-spectrum multidrug-resistant
gram-positive and gram-negative bacteria in food and pharmaceutical purposes.