The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria

Treatment of diabetic foot ulcer (DFU) is of great challenge as it is shown to be infected by multidrug resistant bacteria (MDR bacteria). Sixty four bacterial isolates were isolated from DFU cases; antibiotic susceptibility tests were carried out for all of them. One bacterial isolate (number 11) was shown to resist the action of 8 out of 12 antibiotics used and was identified by both a Vitek-2 system and 16S rRNA fingerprints as belonging to Proteus mirabilis, and was designated Proteus mirabilis LC587231 (P. mirabilis). Clove flower extract (CFE) inhibited distinctively the P. mirabilis bacterium obtained. GC-MS spectroscopy showed that this CFE contained nine bioactive compounds. The effect of CFE on wound healing of Type 1 diabetic albino rats (Rattus norvegicus) was studied. The results indicated that topical application of CFE hydrogel improved wound size, wound index, mRNA expression of the wound healing markers (Coli1, MMP9, Fibronectin, PCNA, and TGF beta), growth factor signaling pathways (PPAR-alpha, PGC1-alpha, GLP-1, GLPr-1, EGF-beta, EGF-beta r, VEGF-beta, and FGF-beta), inflammatory cytokine expression (IL8, TNF alpha, NFK beta, IL1 beta, and MCP1), as well as anti-inflammatory cytokines (IL4 & IL10), pro-apoptotic markers (FAS, FAS-L, BAX, BAX/BCL-2, Caspase-3, P53, P38), as well as an antiapoptotic one (BCL2). Furthermore, it improved the wound oxidative state and reduced the wound microbial load, as the cefepime therapy improved the wound healing parameters. Based on the previous notions, it could be concluded that CFE represents a valid antibiotics alternative for DFU therapy since it improves diabetic wound healing and exerts antibacterial activity either in vitro or in vivo.

Automated summary

In this study, it was found that clove flower extract (CFE) exhibited significant inhibitory effects on multidrug resistant Proteus mirabilis, a bacteria commonly found in diabetic foot ulcers. Furthermore, topical application of CFE hydrogel improved wound healing in Type 1 diabetic albino rats by regulating various wound healing markers, growth factor signaling pathways, inflammatory cytokine expression, and apoptotic markers. Additionally, CFE demonstrated antioxidant and antimicrobial properties. These findings suggest that CFE could be a potential alternative therapy for diabetic foot ulcers.