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

Abstract

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 TGFβ), growth factor signaling pathways (PPAR-α, PGC1-α, GLP-1, GLPr-1, EGF-β, EGF-βr, VEGF-β, and FGF-β), inflammatory cytokine expression (IL8, TNFα, NFKβ, IL1β, 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.

Foam dressing and micropower vacuum dressing promote diabetic foot ulcer wound healing by activating the PI3K/AKT/mTOR pathway in rats

“…37 Excessive secretion of TNF-α, IL-1β, and IL-6 promotes tissue damage, interferes with proliferation and maturation, and thus delays healing of diabetic wounds. 38 In this study, the levels of TNF-α, IL-1β, and IL-6 were found to be considerably higher in the diabetic rat model than that in the controls. Studies have shown that a variety of dressings promote wound healing by inhibiting these inflammatory factors levels.…”

Clove flower extracts (Syzgium aromaticum) increased incision wound epithelization, platelet count, and TGF-β levels in methicillin-resistant Staphylococcus aureus-infected rats

“…The increase in wound healing markers, such as TGF-β, Coli1, MMP-9, proliferating cell nuclear antigen (PCNA), and fibronectin, were indications of wound healing in this study. 22 The TGF-β is known to have pleiotropic effects on wound healing through the regulation of cell proliferation, differentiation, extracellular matrix production, and immune response modulation. An increased level of TGF-β could indicate better wound healing, whereas impaired TGF-β signaling has shown to delay wound healing.…”

Puffball spores improve wound healing in a diabetic rat model

“…Compared with non-diabetic wounds, the diabetic wound healing process has a prolonged the inflammatory stage, with the excessive secretion of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin(IL)-1β, and IL-6. This leads to increased tissue damage, which delays diabetic wound healing by interfering with the proliferation and maturation stages ( 7 ). In long-term hyperglycemia, accumulated advanced glycation end products (AGEs) increase reactive oxygen species (ROS) production ( 8 ).…”