Abstract
Diabetes mellitus is a prevalent cause of mortality worldwide and can lead to several secondary issues, including DWs, which are caused by hyperglycemia, diabetic neuropathy, anemia, and ischemia. Roughly 15% of diabetic patient’s experience complications related to DWs, with 25% at risk of lower limb amputations. A conventional management protocol is currently used for treating diabetic foot syndrome, which involves therapy using various substances, such as bFGF, pDGF, VEGF, EGF, IGF-I, TGF-β, skin substitutes, cytokine stimulators, cytokine inhibitors, MMPs inhibitors, gene and stem cell therapies, ECM, and angiogenesis stimulators. The protocol also includes wound cleaning, laser therapy, antibiotics, skin substitutes, HOTC therapy, and removing dead tissue. It has been observed that treatment with numerous plants and their active constituents, including Globularia Arabica, Rhus coriaria L., Neolamarckia cadamba, Olea europaea, Salvia kronenburgii, Moringa oleifera, Syzygium aromaticum, Combretum molle, and Myrtus communis, has been found to promote wound healing, reduce inflammation, stimulate angiogenesis, and cytokines production, increase growth factors production, promote keratinocyte production, and encourage fibroblast proliferation. These therapies may also reduce the need for amputations. However, there is still limited information on how to prevent and manage DWs, and further research is needed to fully understand the role of alternative treatments in managing complications of DWs. The conventional management protocol for treating diabetic foot syndrome can be expensive and may cause adverse side effects. Alternative therapies, such as medicinal plants and green synthesis of nano-formulations, may provide efficient and affordable treatments for DWs.
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Data availability
The data that supports the findings are available in the manuscript.
Abbreviations
- AGEs:
-
Advanced glycation end-products
- ADSCs:
-
Adipocyte-derived stem cells
- CAT:
-
Catalase
- DWs:
-
Diabetic wounds
- DNA:
-
Deoxyribonucleic acid
- ECM:
-
Extracellular matrix
- EGF:
-
Epidermal growth factor
- EMT:
-
Epithelial–mesenchymal transition
- EPCs:
-
Endothelial progenitor cells
- EST:
-
Electrical stimulation therapy
- FGF:
-
Fibroblast growth factor
- FTIR:
-
Fourier transform infrared spectroscopy
- FESEM:
-
Field emission scanning electron microscopy
- GSH:
-
Glutathione
- GPx:
-
Glutathione peroxidase
- GLUT-1:
-
Glucose transporter-1
- GNPs:
-
Gold nanoparticles
- HIF-1α:
-
Hypoxia inducible factor-1α
- HOTC:
-
Hyperbaric oxygen therapy chamber
- HVMPC:
-
High-voltage monophasic pulsed current
- IL:
-
Interleukin
- IRF:
-
Interferon regulatory factor
- IFN-γ:
-
Interferon-γ
- IGF-1:
-
Insulin-like growth factor-1
- JAK/STAT:
-
Janus kinase/signal transducers and activators of transcription
- LLLT:
-
Low-level laser therapy
- MAPK:
-
Mitogen-activated protein kinase
- miRNA:
-
Micro-ribonucleic acid
- MDA:
-
Malondialdehyde
- MMPs:
-
Matrix metalloproteinase
- NGF:
-
Nerve growth factor
- NPWT:
-
Negative pressure wound therapy
- NF-κB:
-
Nuclear factor kappa B
- PAD:
-
Peripheral arterial disease
- PLGA NPS :
-
Poly-lactic-co-glycolic acid nanoparticle
- PBMT:
-
Photo-bio-modulation therapy
- pDGF:
-
Platelet-derived growth factor
- PGH2:
-
Prostaglandin H2
- PK-C:
-
Protein kinase-C
- ROS:
-
Reactive oxygen species
- SEM:
-
Scanning electron microscope
- SNPs:
-
Silver nanoparticles
- SOD:
-
Superoxide dismutases
- STZ:
-
Streptozotocin
- TNF-α:
-
Tumor necrosis factor-α
- TEM:
-
Transmission electron microscopy
- TGF:
-
Transforming growth factor
- T1DP:
-
Type-1 diabetic patients
- T2DP:
-
Type-2 diabetic patients
- TcPO2:
-
Transcutaneous oxygen pressure
- UPR:
-
Unfolded protein response
- UV–Vis:
-
Ultraviolet–visible spectroscopy
- VEGFR-2:
-
Vascular endothelial growth factor receptor-2
- WHO:
-
World Health Organization
- XRD:
-
X-ray diffraction
- ZnO NPs:
-
Zinc oxide nanoparticles
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Acknowledgements
The authors are very thankful to Shalom Institute of Health and Allied Sciences, Sam Higginbottom University of Agriculture, Technology, Prayagraj, India for facilitating research facilities. The authors extend sincere appreciation to the Honorable Vice Chancellor and the Dean of Rama University for their invaluable support and guidance throughout this project. Furthermore, the author would like to express gratitude toward our esteemed Dean, Prof. Dr. Sonia Pandey, and the faculty of Pharmaceutical Sciences, Kanpur, for their provision of state-of-the-art research facilities and all necessary resources required for conducting this review. The authors are also thankful to GITAM University and DST-FIST Central University of Punjab, for providing necessary fatalities to execute this research.
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Conceptualization and supervision: Dinesh Kumar Patel; DATA collection: Jagat Pal Yadav and Ankit Kumar Singh; writing the manuscript: Jagat Pal Yadav; Sketching of figures: Jagat Pal Yadav, Ankit Kumar Singh; writing, review, and final editing of the manuscript: Amita Verma, Vikas Kumar, Prateek Pathak, Pradeep Kumar, Maria Grishina, and Dinesh Kumar Patel.
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Yadav, J.P., Singh, A.K., Grishina, M. et al. Insights into the mechanisms of diabetic wounds: pathophysiology, molecular targets, and treatment strategies through conventional and alternative therapies. Inflammopharmacol 32, 149–228 (2024). https://doi.org/10.1007/s10787-023-01407-6
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DOI: https://doi.org/10.1007/s10787-023-01407-6