Lipoidal fractions of Zygophyllum simplex exhibit antibacterial and wound-healing activities in a Pseudomonas aeruginosa-infected burn model

Wound care is still a global concern due to the widespread occurrence of bacterial infections, particularly those caused by Pseudomonas aeruginosa (PA), a pathogen known for its intrinsic resistance to multiple antibiotics. This growing resistance underscores the urgent need for alternative therapeutic strategies. Folk medicine has long utilized Zygophyllum simplex L., a traditional medicinal plant, to treat eye infections, inflammation, and a variety of skin conditions, including rough and hardened patches. Nevertheless, there is currently little scientific proof of its dermatological effectiveness, despite its ethnopharmacological significance. In this study, the n-hexane extract of Z. simplex was saponified to yield saponifiable (Sap-ZSHE) and unsaponifiable (Unsap-ZSHE) fractions, which were subsequently analyzed by GC/MS to determine their chemical composition. The antibacterial and wound-healing activities of these lipoidal fractions were evaluated using both in vitro and in vivo models of PA-infected wounds. GC/MS analysis revealed 21 compounds in the Sap-ZSHE, including unsaturated (47 %) and saturated (53 %) fatty acids or their methyl esters and 25 compounds in the Unsap-ZSHE, including a fatty aldehyde (44.91 %), triterpenes (30.9 %), diterpenes (11.61 %), and sterols (8.46 %) as the predominant compounds. The Sap-ZSHE fraction demonstrated the strongest antibacterial activity, with minimum inhibitory concentrations (MICs) of 32–64 µg/mL against PA isolates, significantly surpassing the total n-hexane extract and Unsap-ZSHE (MICs: 256–1024 µg/mL). In vivo evaluation using a PA-infected burn wound model in rats revealed that Sap-ZSHE markedly improved wound healing, as evidenced by reduced bacterial load, accelerated wound closure, enhanced collagen deposition, and normalized histoarchitecture. Immunohistochemical analysis confirmed a reduction in inflammatory markers (TNF-α, IL-6, NF-κB), while qRT-PCR showed upregulation of the tissue repair markers PDGF and fibronectin. These findings demonstrated the therapeutic potential of Z. simplex, particularly its Sap-ZSHE fraction, in treating PA-infected wounds, validating its traditional use and supporting its development as a plant-based alternative for resistant wound infections.