In Vitro Screening of Antimicrobial and Anti-Coagulant Activities, ADME Profiling, and Molecular Docking Study of Citrus limon L. and Citrus paradisi L. Cold-Pressed Volatile Oils

Assia Hamdi; Mabrouk Horchani; Hichem Ben Jannet; Mejdi Snoussi; Emira Noumi; Nouha Bouali; Adel Kadri; Flavio Polito; Vincenzo De Feo; Hayet Edziri

doi:10.3390/ph16121669

In Vitro Screening of Antimicrobial and Anti-Coagulant Activities, ADME Profiling, and Molecular Docking Study of Citrus limon L. and Citrus paradisi L. Cold-Pressed Volatile Oils

Pharmaceuticals (Basel). 2023 Nov 30;16(12):1669. doi: 10.3390/ph16121669.

Authors

Assia Hamdi¹, Mabrouk Horchani², Hichem Ben Jannet², Mejdi Snoussi^{3

4}, Emira Noumi^{3

4}, Nouha Bouali^{3

4}, Adel Kadri^{5

6}, Flavio Polito⁷, Vincenzo De Feo⁷, Hayet Edziri⁸

Affiliations

¹ Laboratory of Chemical, Pharmaceutical and Pharmacological Development of Drugs, Faculty of Pharmacy, University of Monastir, Monastir 5000, Tunisia.
² Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity, Medicinal Chemistry and Natural Products (LR11ES39), Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Avenue of Environment, Monastir 5019, Tunisia.
³ Department of Biology, College of Science, University of Ha'il, Hail 2440, Saudi Arabia.
⁴ Medical and Diagnostic Research Centre, University of Ha'il, Hail 55473, Saudi Arabia.
⁵ College of Science and Arts in Baljurashi, Al Baha University, Al Baha 65527, Saudi Arabia.
⁶ Laboratory of Plant Biotechnology Applied to Crop Improvement, Faculty of Sciences of Sfax, University of Sfax, Sfax 3000, Tunisia.
⁷ Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy.
⁸ Laboratory of Transmissible Diseases and Biologically Active Substances, Faculty of Pharmacy, Monastir 5000, Tunisia.

Abstract

Citrus, which belongs to the Rutaceae family, is a very widespread genus in the Mediterranean Basin. In Tunisia, various parts of these spontaneous or cultivated plants are used in common dishes or in traditional medicine. The purpose of this work was to investigate C. limon and C. paradisi essential oil (EO). The samples were studied for their chemical composition using SPME/MS, as well as their antibacterial and antifungal activities. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) methods were used to evaluate the anticoagulant potentialities. The obtained results show that both essential oils are rich in monoterpenes hydrocarbons, whereby limonene is the main compound in C. paradisi EO (86.8%) and C. limon EO (60.6%). Moreover, C. paradisi EO contains β-pinene (13.3%), sabinene (2.2%) and α-pinene (2.1%). The antibacterial assay of the essential oils showed important bactericidal and fungicidal effects against all strains tested. In fact, the MICs values of C. limon EO ranged from 0.625 to 2.5 mg/mL against all Gram-positive and Gram-negative bacteria, and from 6.25 to 12.5 mg/mL for Candida spp. strains, while C. paradisi EO was more active against all bacteria with low MICs values ranging from 0.192 to 0.786 mg/mL, and about 1.5 mg/mL against Candida species. Both tested Citrus EOs exhibited interesting anticoagulant activities as compared to heparin. The molecular docking approach was used to study the binding affinity and molecular interactions of all identified compounds with active sites of cytidine deaminase from Klebsiella pneumoniae (PDB: 6K63) and the C (30) carotenoid dehydrosqualene synthase from Staphylococcus aureus (PDB: 2ZCQ). The obtained results show that limonene had the highest binding score of -4.6 kcal.mol^-1 with 6K63 enzyme, and -6.7 kcal.mol^-1 with 2ZCQ receptor. The ADME profiling of the major constituents confirmed their important pharmacokinetic and drug-like properties. Hence, the obtained results highlight the potential use of both C. limon and C. paradisi essential oils as sources of bioactive compounds with antibacterial, antifungal, and anti-coagulant activities.

Keywords: ADME; Citrus species; anti-coagulant; antibacterial; cold press; docking study; essential oils.

Grants and funding

MDR-22 021/Scientific Research Deanship at University of Ha'il - Saudi Arabia