Dehydrozingerone promotes healing of diabetic foot ulcers: a molecular insight

Abstract

Introduction One of the most common problems of diabetes are diabetic foot ulcers (DFUs). According to National Institute for Health, initial management of DFUs can decrease the complication of limb amputations and can improve the patient’s quality of life. DFU treatment can be optimized with the help of multidisciplinary approach. Based on many studies, control of glucose levels in blood, antioxidant activity, reduction in cytokine levels, re-epithelialization, collagen formation, migration of fibroblasts are major phases involved in managing DFU. Dehydrozingerone (DHZ), has been known for its anti-inflammatory, antioxidant and wound healing properties. Methodology Three months high-fat diet and low dose of streptozotocin-induced type-II diabetic foot ulcer model was used to evaluate the effectiveness of dehydrozingerone. DHZ was given orally to rats for 15 days post wounding. TNF-α, IL-1β and antioxidant parameters like lipid peroxidation, glutathione reductase were estimated. Immunoblotting was done to investigate the effect of DHZ on the expression of ERK, JNK, HSP-27, P38, SIRT-1, NFκB, SMA, VEGF and MMP-9 in skin tissue. Histopathology was performed for analyzing DHZ effect on migration of fibroblasts, formation of epithelium, granulation tissue formation, angiogenesis and collagen formation. Results DHZ decreased the levels of malondialdehyde, TNF-α, IL-1β and increased glutathione levels in wound tissue. Western blotting results suggested that DHZ activated ERK1/2/JNK/p38 signaling, increased expression of HSP-27, SIRT-1, VEGF, SMA thus facilitating the migration and proliferation of fibroblasts, angiogenesis and decreased inflammation. Masson Trichrome & histopathology showed an increase in collagen, epithelial and granulation tissue formation. Conclusion DHZ significantly accelerates the healing of diabetic foot ulcers in high fat diet fed plus low dose streptozotocin induced type-II diabetic Wistar rats. Graphical abstract

Investigation of the cellular and molecular effects of dehydrozingerone formulation on various days of diabetic wound repair

“…The membrane was washed three times, 10 min each, using TBST, then incubated with the primary antibodies ERK, p-ERK, JNK, p-JNK, AMPK, pAMPK, VEGF, MMP-2, MMP-9, TNF-α (1:1000) and COL-1 (1:500) at 4 °C overnight, followed by incubation with horseradish peroxidase-conjugated anti-IgG Secondary antibody (1:10,000) for 2 h. The blots were detected using ECL solution (Westar Antares, Cyanagen, Bologna, Italy) in Syngene GBox Chemi XRQ gel documentation system. Quantification of protein band intensity was done using ImageJ software and relative density was calculated in comparison to alpha-tubulin expression (Begum et al 2023 ).…”

“…5 µm-thick sections of paraffin-fixed tissue were achieved and staining was done using hematoxylin and eosin and Masson trichrome. Slides were examined under light microscope (Begum et al 2023 ).…”

Development and optimization of kaempferol loaded ethosomes using Box–Behnken statistical design: In vitro and ex‐vivo assessments

“…Phytotherapy is generally thought to be less toxic than synthetic therapeutic agents, making it an excellent choice for DFU management 4 . Numerous plant compounds, including resveratrol, curcumin, sesamol, and naringin, have been chemically synthesized and tested with promising results for accelerating the healing of foot ulcers through a variety of mechanisms 5 …”

“…4 Numerous plant compounds, including resveratrol, curcumin, sesamol, and naringin, have been chemically synthesized and tested with promising results for accelerating the healing of foot ulcers through a variety of mechanisms. 5 One such plant-based substance is KMP (3,5,7-trihydroxy-2-[4-hydroxyphenyl]-4H-1-benzopyran-4-one) has a low molecular weight (286.2 g/mol). It can be found in traditional medicines such as Sophora japonica, ginkgo, and galangal, as well as foods, such as beans, cauliflower, cabbage, gooseberries, grapes, cabbage, strawberries, tea, and tomatoes.…”

Neuroprotective Effects of the Nutraceutical Dehydrozingerone and Its C2-Symmetric Dimer in a Drosophila Model of Parkinson’s Disease

“…It has been demonstrated that DHZ exhibits many biological activities and pharmacological properties, including anti-inflammatory, antioxidant, anti-obesity, anti-cancer, tyrosinase-inhibitory, neuroprotective, antidepressant and anti-fungal effects [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”