Journal of ethnopharmacology · 2025
Deciphering phenolic-rich fractions from Caesalpinia pulcherrima (L.) with integrative metabolomic and in silico insights into efflux protein inhibition.
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Seukep Armel Jackson, Mbuntcha Helene Gueaba, Matieta Valaire Yemene, Zanchi Fernando Berton, Zemnou Cromwel Tepap, Kuete Victor, Guo Mingquan
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia pulcherrima (CP), native to tropical America and used across Asia and Africa, is valued for managing bacterial infections. However, its resistance-modulatory potential remains largely unexplored.
AIM OF THE STUDY: To investigate the antibacterial and resistance-modulating potential of CP extracts and metabolites through integrated in vitro, metabolomics, and computational analyses.
MATERIALS AND METHODS: Crude hydromethanolic extracts from CP flowers (CPF), bark (CPB), leaves, and fruits were prepared by ultrasound extraction. Antibacterial and resistance modulatory assays were performed by broth microdilution. CPF and CPB were fractionated with solvents of increasing polarity, and bioactive fractions were profiled by LC/Q-TOF-MS. Identified metabolites were evaluated for ADMET, molecular docking, and 100-ns molecular dynamics simulations (MDS) against BamB, OprM, and NorA efflux proteins.
RESULTS: Crude extracts exhibited broad-spectrum antibacterial activity against 29 multidrug-resistant strains (MICs: 8-1024 μg/mL). CPB and CPF displayed superior efficacy, with ethyl acetate (EtOAc) fractions markedly potent; CPF-EtOAc achieved MICs <100 μg/mL against 86 % of tested strains. These fractions synergistically potentiated multiple antibiotics, lowering MICs by 2-128-fold. Metabolomic profiling identified 88 metabolites (45 in CPB-EtOAc, 43 in CPF-EtOAc), predominantly phenolic compounds, including previously unreported phytochemicals in this species. Four lead compounds (naringenin, acacetin, dehydrovariabilin, and 3',7-dimethoxy-3-hydroxyflavone) exhibited favorable ADMET and strong docking affinities (-6.2 to -8.0 kcal/mol). MDS confirmed stable complexes, with dehydrovariabilin showing the lowest RMSD (0.48 Å in BamB, 0.53 Å in NorA) and highest compactness, indicating superior binding stability.
CONCLUSION: The bark and flowers of C. pulcherrima represent valuable sources of phytochemicals with dual antibacterial and resistance-modifying activities, supporting their ethnomedicinal relevance and their potential as leads for novel antimicrobial adjuvants.
AIM OF THE STUDY: To investigate the antibacterial and resistance-modulating potential of CP extracts and metabolites through integrated in vitro, metabolomics, and computational analyses.
MATERIALS AND METHODS: Crude hydromethanolic extracts from CP flowers (CPF), bark (CPB), leaves, and fruits were prepared by ultrasound extraction. Antibacterial and resistance modulatory assays were performed by broth microdilution. CPF and CPB were fractionated with solvents of increasing polarity, and bioactive fractions were profiled by LC/Q-TOF-MS. Identified metabolites were evaluated for ADMET, molecular docking, and 100-ns molecular dynamics simulations (MDS) against BamB, OprM, and NorA efflux proteins.
RESULTS: Crude extracts exhibited broad-spectrum antibacterial activity against 29 multidrug-resistant strains (MICs: 8-1024 μg/mL). CPB and CPF displayed superior efficacy, with ethyl acetate (EtOAc) fractions markedly potent; CPF-EtOAc achieved MICs <100 μg/mL against 86 % of tested strains. These fractions synergistically potentiated multiple antibiotics, lowering MICs by 2-128-fold. Metabolomic profiling identified 88 metabolites (45 in CPB-EtOAc, 43 in CPF-EtOAc), predominantly phenolic compounds, including previously unreported phytochemicals in this species. Four lead compounds (naringenin, acacetin, dehydrovariabilin, and 3',7-dimethoxy-3-hydroxyflavone) exhibited favorable ADMET and strong docking affinities (-6.2 to -8.0 kcal/mol). MDS confirmed stable complexes, with dehydrovariabilin showing the lowest RMSD (0.48 Å in BamB, 0.53 Å in NorA) and highest compactness, indicating superior binding stability.
CONCLUSION: The bark and flowers of C. pulcherrima represent valuable sources of phytochemicals with dual antibacterial and resistance-modifying activities, supporting their ethnomedicinal relevance and their potential as leads for novel antimicrobial adjuvants.