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Therapeutic targeting of ocular diseases with emphasis on PI3K/Akt, and OPRL pathways by Hedera helix L. saponins: a new approach for the treatment of Pseudomonas aeruginosa-induced bacterial keratitis |
| Sherif A. Hamdy1, Shymaa Hatem2, Heba Elosaily3, Abrar Gomaa Abd-Elfattah Hassan4, Rana Elshimy5,6, Ahmed H. Osman7, Riham A. El-Shiekh1 |
1. Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt;
2. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University in Egypt, New Cairo, Egypt;
3. Biochemistry Department, Faculty of Pharmacy, Ahram Canadian University, 4th Industrial Region, 6th of October City, 12585, Giza, Egypt;
4. Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11765, Egypt;
5. Department of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt;
6. Department of Microbiology and Immunology, Egyptian Drug Authority, Cairo, Egypt;
7. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt |
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Abstract Pseudomonas aeruginosa-induced bacterial keratitis is one of the most sight-threatening corneal infections associated with intense ocular inflammatory reactions that may lead to vision loss. Hence, this study investigated the efficacy of three nanocomposite chitosan-coated penetration enhancer vesicles (PEVs) to augment the ocular delivery of saponin(s), α-hederin (PEVI), hederacoside C (PEVII), or both (PEVIII) for treatment of Pseudomonas keratitis and its induced inflammatory response. The three formulations were prepared using the ethanol injection method and comprehensively characterized. In vitro, the antibacterial activity of the three formulations against P. aeruginosa was evaluated using agar well-diffusion method, pyocyanin production inhibition, and swarming and twitching motility inhibition assays. The therapeutic effect of the three formulations has been investigated in P. aeruginosa keratitis by gross lesion monitoring, determination of bacterial bioburden, biochemical markers, histopathological examination, and scoring after 7 days of topical treatment. Data revealed that PEVI, PEVII, and PEVIII nanocomposites showed particle size in the nanometer range, high entrapment efficiency, good stability, and sustained release of the saponins throughout 24 h. Among them, PEVIII exhibited notably strong in vitro antipseudomonal activity. Additionally, animals treated topically with PEVIII showed an appreciable gross lesion reduction, corneal tissue improvement, and formidable bacterial load reduction compared with untreated and gentamicin sulfate eye (GENTAWISE®) ointment-treated groups. Moreover, PEVIII treatment showed the most significant reduction in TNF-α, NF-κB, ROS levels, and OPRL virulence gene expression while enhancing PI3K/Akt activation. Therefore, this study offers PEVIII as a promising treatment for P. aeruginosa keratitis.
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| Keywords
Hedera helix L.
Saponins
α-Hederin
Hedracoside C
Pseudomonas keratitis
Eye disease
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| Fund:This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. |
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Issue Date: 18 June 2025
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