**5.5 Natural products**

Aloe Vera, *Salvia miltiorrhiza*, *Mimosa tenuiflora*, *Alchemilla vulgaris*, *Angelica sinensis*, and *Moringa oleifera* are just a few of the plants utilized in a variety of cosmetic goods such as ointments, lotions, and gels. *M. oleifera* has been proven to drastically lower the levels of numerous cytokines, including but not limited to TNF-6, IL-6, and VEGF, as well as promote tissue granulation and reduce the size of diabetic foot ulcer wounds [39, 40]. Honey has healing, non-harmful antibacterial, antioxidant, and anti-inflammatory qualities that aid in the healing of burns and wounds. As an alternative therapy for diabetic foot ulcer, honey therapy has attracted a lot of interest in recent years and several studies have evaluated the effectiveness of honey therapy for treating diabetic foot ulcer at different stages [41, 42]. A recent study compared traditional saline solution dressings to honey dressings and found that the latter were more effective in terms of healing time and the number of lesions that were healed after 120 days [12, 43].

### **5.6 Bacteriophages**

Bacteriophages are viruses that identify and reproduce in bacterial cells. Bacteriophages contain capsid protein heads that transport and protect the virus's genetic material [44]. The genetic material's size, organization (circular, linear, or segmented), and structure might change depending on the virus (ssDNA, dsDNA, ssRNA, dsRNA). Based on the bacteriophage used and the target proteins that aid in bacterial host attachment, bacteriophages are very host specific and will only attack specific strains [45]. Phages have so far been found to be successful in treating bacterial illnesses including cystic fibrosis, eye infections, new-born sepsis, urinary tract illnesses, and malignancies, in addition to skin infections brought on by bacteria like *P. aeruginosa*, *S. aureus*, *K. pneumoniae*, and *E. coli* [46]. According to Khalifa et al. [47] Myoviridae bacteriophage EFLK1 was successfully identified against the phage-resistant strain of Vancomycin-resistant *E. faecalis* V583 and due to genetic superiority, even phage-resistant bacteria can be eliminated by other phages from the same host in this research. According to El-Shibiny and El-Sahhar [48], bacteriophage T4 and the antibiotic cefotaxime can be used in combination to treat *E. coli* biofilms, although phage therapy can also be used on its own to clear them [49].

### **5.7 Probiotics therapy**

One of these novel substances that is both commonly used and thoroughly researched for its potential to promote health is probiotics [50]. Probiotics are either a single strain or a combination of several organisms, and they have the power to improve wound healing after an inflammatory cell build-up at the wound site, boost immune systems, and produce anti-inflammatory action [19–26, 42–46, 49–51].

Recent randomized controlled trial experiments have demonstrated that certain intestinal bacteria, such as Lactobacillus and Bifidobacteria, inhibit cariogenic streptococci and Candida spp., and have positive effects on their oral action [52].
