Patients with diabetes mellitus often suffer from chronic wounds due to wound healing impairment. Considering the increased prevalence of diabetes, this would predispose significant medical, economic, and social problems. These chronic wounds are frequently infected with pathogenic bacteria like Pseudomonas aeruginosa, which complicates the situation and makes the wound healing process more difficult. Therefore, there is a high need for therapeutic alternatives to the currently available treatments. Plants are vital sources of many bioactive compounds with multiple biological activities. We elucidated the wound healing possibility and antibacterial effect of Cycas thouarsii n-butanol fraction (CTBF) for the first time. Also, CTBF's phytochemical fingerprint was investigated using the LC-MS/MS technology. Interestingly, CTBF revealed antibacterial activity against P. aeruginosa isolates with minimum inhibitory concentrations range 16-128 µg/mL. Regarding the wound healing potential, we used in vivo experiment on diabetic rats. Remarkably CTBF caused a significant reduction (p 0.05) in the levels of forkhead box O1, matrix metalloproteinases 9, and chemokine (C-C motif) ligand 20. Additionally, it led to a substantial increase (p 0.05) in the level of transforming growth factor β1. Moreover, CTBF improved the wound histological features by increasing the collagen area percentage. Regarding the immunohistochemical studies, CTBF resulted in a strong positive epidermal growth factor and a moderate positive caspase 9 immunoreaction in the epidermis and sebaceous glands of the wounds. Therefore, CTBF could be a promising source of bioactive compounds with wound healing and antibacterial activities. Finally, molecular docking was attempted using MOE software to investigate the binding mode of the major identified compounds in the matrix metalloproteinase 9 (MMP-9) receptor (PDB code: 1GKC).
Keywords: Biochemical assessment; Immunostaining; Molecular docking simulation; Phytochemical fingerprint; Pseudomonas aeruginosa; Skin wound model.
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