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Peer-reviewedCC BYFrontiers in pharmacology

Phenolic metabolites from Ceratonia siliqua L. pods: chemical characterization, soybean lipoxygenase-1 inhibition, and in vitro gallstone-dissolving capacity

1 more authors
9 affiliations
  1. 1Laboratory of Bioeconomics, Food Safety, and Health, Department of Food Science, Faculty of Natural Sciences and Life, University of Abdelhamid Ibn Badis , ,
  2. 2Laboratory of Sciences and Techniques of Valorization (STEVA), Faculty of Natural Sciences and Life, University of Abdelhamid Ibn Badis , ,
  3. 3Laboratory of Plant Protection, Faculty of Natural Sciences and Life, University of Abdelhamid Ibn Badis , ,
  4. 4Hospital Center University Beni Messous , ,
  5. 5Research Laboratory for Crop Production and Protection in Chlef Region, Faculty of Natural Sciences and Life, University of Hassiba Benbouali , ,
  6. 6Laboratoire de Biotechnologies et Protection des Ecosystèmes Agricoles et Naturels, Faculté des Sciences de la Nature et de la Vie et Sciences de la Terre, Université de Bouira , ,
  7. 7Malaysian Institute of Marine Engineering Technology (UniKL MIMET), Universiti Kuala Lumpur , , ,
  8. 8Laboratory of Biomaterials and Transport Phenomena (LBMTP), University Yahia Fares , ,
  9. 9School of Engineering, Newcastle University , ,

Abstract

Introduction: Carob (Ceratonia siliqua L., Fabaceae) is a Mediterranean tree whose pods are rich in phenolic metabolites and are credited with antioxidant, anti-inflammatory,hypolipidemic and antimicrobial properties.

Methods: The chemical composition of MECp was determined by high-performance liquid chromatography coupled with ultraviolet detection (HPLC/UV). Free radical-scavenging and ferric-reducing capacities were measured using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP) analytical descriptors assays, and soybean LOX-1 inhibition was assessed in vitro and examined in silico by molecular docking against the enzyme (PDB ID: 3O8Y). Gallstones removed at surgery were confirmed as cholesterol stones by Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and then incubated in MECp under continuous agitation for 4 weeks, with a sodium chloride solution (NaCl, 9 g/L) as control. Gallstone mass after drying at 40 °C, the percentage of gallstone-dissolving capacity (% GDC) and the pH of the medium were recorded weekly.

Results: HPLC/UV analysis identified 20 phenolic metabolites in MECp. The extract contained 160.68 mg GAE/g DE of total phenolics and 9.19 mg QE/g DE of total flavonoids, with median inhibitory concentrations (IC50) of 0.16, 0.86 and 0.19 mg/mL for the DPPH, FRAP and soybean LOX-1 inhibition assays, respectively. Compared with the control, MECp produced a highly significant increase in % GDC over time, and the docking analysis revealed strong and stable interactions between the major polyphenols and the soybean LOX-1 active site.

Discussion: The dissolution obtained with MECp is consistent with its phenolic composition, and the docking results agree with the soybean LOX-1 inhibition measured in vitro. These findings identify MECp as a promising natural candidate for cholesterol gallstone management and support further preclinical investigation.

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BibTeX
@article{mekraf2026phenolic,
  title = {{Phenolic metabolites from Ceratonia siliqua L. pods: chemical characterization, soybean lipoxygenase-1 inhibition, and in vitro gallstone-dissolving capacity}},
  author = {Souheyla Mekraf and Mokhtaria Yasmina Boufadi and Fatiha Abbassene and Kamal Nedjari Benhadj Ali and Abdelkrim Chetibi and Soumia Keddari and Malika Meziane and Mohammed Bouzouina and Hamza Moussa and Zulzamri Salleh and Hichem Tahraoui and Jie Zhang and Abdeltif Amrane},
  journal = {Frontiers in pharmacology},
  year = {2026},
  month = sep,
  doi = {10.3389/fphar.2026.1945402},
  url = {https://europepmc.org/article/PMC/PMC13661950},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Phenolic metabolites from Ceratonia siliqua L. pods: chemical characterization, soybean lipoxygenase-1 inhibition, and in vitro gallstone-dissolving capacity
AU  - Souheyla Mekraf
AU  - Mokhtaria Yasmina Boufadi
AU  - Fatiha Abbassene
AU  - Kamal Nedjari Benhadj Ali
AU  - Abdelkrim Chetibi
AU  - Soumia Keddari
AU  - Malika Meziane
AU  - Mohammed Bouzouina
AU  - Hamza Moussa
AU  - Zulzamri Salleh
AU  - Hichem Tahraoui
AU  - Jie Zhang
AU  - Abdeltif Amrane
PY  - 2026
DA  - 2026/09/30
JO  - Frontiers in pharmacology
DO  - 10.3389/fphar.2026.1945402
UR  - https://europepmc.org/article/PMC/PMC13661950
AB  - Introduction: Carob (Ceratonia siliqua L., Fabaceae) is a Mediterranean tree whose pods are rich in phenolic metabolites and are credited with antioxidant, anti-inflammatory,hypolipidemic and antimicrobial properties.  Methods: The chemical composition of MECp was determined by high-performance liquid chromatography coupled with ultraviolet detection (HPLC/UV). Free radical-scavenging and ferric-reducing capacities were measured using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric-reducing antioxidant power (FRAP) analytical descriptors assays, and soybean LOX-1 inhibition was assessed in vitro and examined in silico by molecular docking against the enzyme (PDB ID: 3O8Y). Gallstones removed at surgery were confirmed as cholesterol stones by Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and then incubated in MECp under continuous agitation for 4 weeks, with a sodium chloride solution (NaCl, 9 g/L) as control. Gallstone mass after drying at 40 °C, the percentage of gallstone-dissolving capacity (% GDC) and the pH of the medium were recorded weekly.  Results: HPLC/UV analysis identified 20 phenolic metabolites in MECp. The extract contained 160.68 mg GAE/g DE of total phenolics and 9.19 mg QE/g DE of total flavonoids, with median inhibitory concentrations (IC50) of 0.16, 0.86 and 0.19 mg/mL for the DPPH, FRAP and soybean LOX-1 inhibition assays, respectively. Compared with the control, MECp produced a highly significant increase in % GDC over time, and the docking analysis revealed strong and stable interactions between the major polyphenols and the soybean LOX-1 active site.  Discussion: The dissolution obtained with MECp is consistent with its phenolic composition, and the docking results agree with the soybean LOX-1 inhibition measured in vitro. These findings identify MECp as a promising natural candidate for cholesterol gallstone management and support further preclinical investigation.
SN  - 1663-9812
ER  -