Frontiers in pharmacology · 2026
Potential of isoquinoline-alkaloid-rich Papaveraceae extracts against bacteria causing ocular infections - In vitro and In vivo study.
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Dzięgielewska Monika, Zielińska Sylwia, Khan Taimoor, Qudus Muhammad Suahib, Dudek Bartłomiej, Brożyna Malwina, Kozłowska Weronika, Matkowski Adam, Bartoszewicz Marzenna, Sun Yanfang, Junka Adam
Аннотация
INTRODUCTION: There is an evident need for novel ophthalmic therapeutics that operate outside the conventional antibiotic and chemically synthetized antiseptic paradigms. Medicinal plants represent a chemically rich and cost-effective source of bioactive compounds, though their use requires careful toxicological assessment.
METHODS: In this study, extracts from four Papaveraceae species - Chelidonium majus (roots), Corydalis cheilanthifolia (aerial parts and roots), Glaucium flavum (aerial parts and roots), and Fumaria officinalis (herb) - were investigated across three experimental levels: in silico, in vitro, and in vivo, using the Galleria mellonella larval model.
RESULTS: Chemical profiling identified several isoquinoline alkaloids, including berberine, coptisine, protopine, chelidonine, allocryptopine, glaucine, and tetrahydropalmatine. In silico assessment suggested low systemic toxicity but possible blood-brain barrier permeability for some compounds. In vitro antimicrobial testing against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 15442, performed using broth microdilution and bacterial-cellulose-based diffusion assays, demonstrated moderate but reproducible activity of extracts, particularly in Ch. majus roots (MIC equal 1.56 mg/mL for S. aureus and 6.25 mg/mL for P. aeruginosa) and in C. cheilanthifolia, where depending on the type of extract (herb_2, herb_1, root), range of MIC was 0,78-1.56 mg/mL for S. aureus and 3,12-6,25 mg/mL for P. aeruginosa. Cytotoxicity testing on fibroblast cell lines showed no significant toxicity in applied concentrations. In vivo testing showed that all extracts, except C. cheilanthifolia (herb_1) and Ch. majus (root) were virtually non-lethal to G. mellonella larvae, indicating a favorable safety profile in 0.05 mg/mL to 0.002 mg/mL concentrations. To evaluate their suitability for ocular application, wettability tests were performed using commercial tear substitute formulations. The incorporation of the C. cheilanthifolia herb_2 extract at bactericidal concentrations did not alter these physicochemical properties.
DISCUSSION: Overall, the Papaveraceae extracts demonstrated moderate antibacterial activity and low cytotoxicity in applied concentrations, supporting their potential use as adjuvant components in eye drop formulations - enhancing therapeutic efficacy, reducing required antiseptic dosage, and potentially lowering the risk of resistance development.
METHODS: In this study, extracts from four Papaveraceae species - Chelidonium majus (roots), Corydalis cheilanthifolia (aerial parts and roots), Glaucium flavum (aerial parts and roots), and Fumaria officinalis (herb) - were investigated across three experimental levels: in silico, in vitro, and in vivo, using the Galleria mellonella larval model.
RESULTS: Chemical profiling identified several isoquinoline alkaloids, including berberine, coptisine, protopine, chelidonine, allocryptopine, glaucine, and tetrahydropalmatine. In silico assessment suggested low systemic toxicity but possible blood-brain barrier permeability for some compounds. In vitro antimicrobial testing against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 15442, performed using broth microdilution and bacterial-cellulose-based diffusion assays, demonstrated moderate but reproducible activity of extracts, particularly in Ch. majus roots (MIC equal 1.56 mg/mL for S. aureus and 6.25 mg/mL for P. aeruginosa) and in C. cheilanthifolia, where depending on the type of extract (herb_2, herb_1, root), range of MIC was 0,78-1.56 mg/mL for S. aureus and 3,12-6,25 mg/mL for P. aeruginosa. Cytotoxicity testing on fibroblast cell lines showed no significant toxicity in applied concentrations. In vivo testing showed that all extracts, except C. cheilanthifolia (herb_1) and Ch. majus (root) were virtually non-lethal to G. mellonella larvae, indicating a favorable safety profile in 0.05 mg/mL to 0.002 mg/mL concentrations. To evaluate their suitability for ocular application, wettability tests were performed using commercial tear substitute formulations. The incorporation of the C. cheilanthifolia herb_2 extract at bactericidal concentrations did not alter these physicochemical properties.
DISCUSSION: Overall, the Papaveraceae extracts demonstrated moderate antibacterial activity and low cytotoxicity in applied concentrations, supporting their potential use as adjuvant components in eye drop formulations - enhancing therapeutic efficacy, reducing required antiseptic dosage, and potentially lowering the risk of resistance development.