Wound Healing Potential of the Standardized Extract of Boswellia serrata on Experimental Diabetic Foot Ulcer via Inhibition of Inflammatory, Angiogenetic and Apoptotic Markers

Planta Medica ◽  
2019 ◽  
Vol 85 (08) ◽  
pp. 657-669 ◽  
Author(s):  
Zhang Pengzong ◽  
Li Yuanmin ◽  
Xiong Xiaoming ◽  
Deng Shang ◽  
Xiong Wei ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Diabetic Foot ◽  
Nitrosative Stress ◽  
Transforming Growth Factor ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Boswellia Serrata ◽  
Endothelial Growth Factor

AbstractThe aim of the present study was to evaluate the wound healing potential and possible mechanism of action of the standardized extract of Boswellia serrata against the experimental model of diabetic foot ulcer. α-Boswellic acid was isolated from the standardized extract of B. serrata and characterized (HPLC, 1H-NMR, 13C-NMR, ESI-MS). Diabetes was induced in Sprague-Dawley rats by streptozotocin (55 mg/kg, i. p.), and wounds were created on the dorsal surface of the hind paw. B. serrata (100, 200, and 400 mg/kg, p. o.) was administered to the rats for 16 days. The HPLC analysis showed a single peak with a retention time of 12.51 min. The compound was identified with ESI-MS [M + Na]+ = 455.37 as α-boswellic acid. Treatment with B. serrata (200 and 400 mg/kg) significantly increased the rate of wound contraction via modulation of oxido-nitrosative stress and elevated the hydroxyproline level at the wound area. reverse transcription-PCR analysis revealed that streptozotocin-induced increases in TNF-α, interleukin-1β, interleukin-6, nuclear factor-kappa-light-chain-enhancer of activated B cells, and Bcl-2-associated X protein, and decreases in angiopoietin-1, Tie2, transforming growth factor beta 1, vascular endothelial growth factor, and collagen-1 mRNA expression were significantly inhibited by B. serrata. It also significantly reduced wound cellular necrosis as evaluated by flow cytometry using propidium iodide fluorescence intensity. Streptozotocin-induced histopathological alterations were also significantly ameliorated by B. serrata. In conclusion, standardized extracts of B. serrata exert its wound healing potential via orchestrating mechanisms, which include the inhibition of oxido-inflammatory markers (oxido-nitrosative stress, TNF-α, interleukins, and nuclear factor-kappa-light-chain-enhancer of activated B cells), increased collagen synthesis (hydroxyproline and collagen-1) and angiogenesis (Ang-1/Tie2), promoting growth factors (transforming growth factor beta 1 and vascular endothelial growth factor), and inhibition of apoptosis (Bcl-2-associated X protein) to accelerate wound healing in experimental delayed diabetic foot ulcer.

Epidermal Vascular Endothelial Growth Factor Improved Wound Healing of Patients with Diabetic Foot Ulcer

2018 ◽  
Vol 24 (8) ◽  
pp. 6136-6139
Author(s):  
Maria Francisca Ham ◽  
Pradana Soewondo ◽  
Saphora Dien ◽  
Kusmardi Kusmardi ◽  
Mpu Kanoko
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Diabetic Foot ◽  
Standard Procedure ◽  
Vascular Complications ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Complex Process ◽  
Proximal Site ◽  
Endothelial Growth Factor

Diabetic foot ulcer (DFU) is a kind of chronic vascular complications in diabetes. Wound healing in DFU is a complex process where reduced proangiogenic growth factor is an important factor. We studied angiogenesis factors which may contribute to the healing of DFU. Twenty five type 2 diabetes patients with acute DFU were treated with hospital standard procedure and closely observed for 1 month. Biopsies from wound edges were subjected to histopathology assessment and immunohistochemical staining of CD34, bFGF and VEGF. All examination was performed two times consecutively. We observed that granulation tissues developed faster at proximal site of the foot. Weak tissue VEGF was expressed before treatment. Interestingly, VEGF expression in epidermis increased significantly after patients received treatment. Increased VEGF is consistent with increased number of CD34 positive endothelial cells. These data suggest that epidermal VEGF is an important angiogenesis factor and may improve healing in acute DFU receiving standard treatment.

scholarly journals Peningkatan Ekspresi Transforming Growth Factor Beta 1 (TGF β1) Pada Luka Diabetes Melitus Melalui Balutan Modern

2010 ◽  
Vol 13 (1) ◽  
pp. 20-25
Author(s):  
Heri Kristianto ◽  
Elly Nurachmah ◽  
Dewi Gayatri
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Immunohistochemical Analysis ◽  
Consecutive Sampling ◽  
Quasi Experimental ◽  
Growth Factor Beta ◽  
Diabetes Melitus

AbstrakEkspresi transforming growth factor beta 1 pada luka diabetes melitus mengalami penurunan yang berdampak terhadap proses penyembuhan luka. Penelitian ini bertujuan untuk membandingkan perawatan luka modern dressing dengan metode konvensional terhadap ekspresi transforming growth factor beta 1 pada luka kaki diabetes melitus. Penelitian menggunakan quasi experimental pretest-posttest design dengan metode pengumpulan sampel secara consecutive sampling. Pengukuran ekspresi transforming growth factor beta 1 dilakukan pada hari ke-0 (pretest) dan ke-4 (posttest). Hasil penelitian didapatkan data pada kelompok modern terjadi peningkatan ekspresi transforming growth factor beta 1, sedangkan pada kelompok konvensional terjadi penurunan ekspresi transforming growth factor beta 1. Disimpulkan bahwa teknik perawatan luka secara modern mampu meningkatkan ekspresi transforming growth factor beta 1dibandingkan teknik konvensional pada luka kaki diabetes melitus. AbstractReduction of expression of transforming growth factor beta 1 in diabetic ulcers affects overall wound healing. This study tried to draw a comparison of transforming growth factor beta 1 level between modern dressing and conventional dressing in diabetic foot ulcer. This study applied a quasi-experimental pretest-posttest design and a consecutive sampling method of data collection. Immunohistochemical analysis of transforming growth factor beta 1 level was measured on the day 0 (pretest) and the day 4 (posttest). In this study, the modern dressing application improves transforming growth factor beta 1 level. Meanwhile, the conventional dressing application decreases transforming growth factor beta 1 level. Thus, it can be concluded that the modern dressing application can increase transforming growth factor beta 1 level.

scholarly journals Hyaluronic Acid Accelerates VEGF and PDGF Release from Advance Platelet Rich Fibrin in Diabetic Foot Ulcer

2021 ◽  
Vol 13 (3) ◽  
pp. 332-6
Author(s):  
Ronald Winardi Kartika ◽  
Idrus Alwi ◽  
Franciscus Dhyanagiri Suyatna ◽  
Ferry Sandra ◽  
Em Yunir ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Growth Factor ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Vascular Endothelial ◽  
Platelet Rich Fibrin ◽  
Growth Factor Release ◽  
Endothelial Growth Factor ◽  
Factor Release

BACKGROUND: Hyaluronic acid (HA) is an essential component of extracellular matrix and mediates signaling in wound healing. HA could induce growth factor release from Advanced Platelet Rich Fibrin (A-PRF), including Vascular Endothelial Growth Factor (VEGF) and Platelet-derived Growth Factor (PDGF). However, concentrations of the released-VEGF and PDGF have not been clearly disclosed. Therefore, current study was conducted to measure the release of these growth factors in HA + A-PRF gel of diabetic foot ulcer (DFU) subjects.METHODS: Twenty DFU subjects were included in the study and treated with A-PRF or HA+A-PRF. A-PRF was derived from autologous peripheral blood and processed with low-speed centrifugation. HA was added with a ratio of 1:0.6. A-PRF or HA + A-PRF was applied topically on DFU. Upper tips of A-PRF or HA + A-PRF gels were collected on day 0, 3 and 7 for measurements of VEGF and PDGF concentrations with Enzyme-linked Immune-sorbent Assay (ELISA) methods.RESULTS: On day-3, both VEGF and PDGF concentrations of HA + A-PRF group were significantly higher than the VEGF (p=0.000) and PDGF (p=0.019) concentrations of A-PRF group. The VEGF and PDGF concentrations were continuously and significantly increased on day-7 of HA + A-PRF group, compared to the VEGF (p=0.000) and PDGF (p=0.004) concentrations of A-PRF group.CONCLUSION: Combination HA+A-PRF induces VEGF and PDGF release from A-PRF. A mixture of A-PRF and HA could be more effective than A-PRF alone for treatment of DFU.KEYWORDS: hyaluronic acid, advanced platelet rich fibrin, PRF, growth factor, VEGF, PDGF, diabetic foot ulcer

scholarly journals Hesperidin enhances angiogenesis via modulating expression of growth and inflammatory factor in diabetic foot ulcer in rats

2018 ◽  
Vol 16 ◽  
pp. 205873921877525 ◽  
Author(s):  
Li Wang ◽  
Ting He ◽  
Adan Fu ◽  
Zhijin Mao ◽  
Lan Yi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Control Group ◽  
Diabetic Patients ◽  
Inflammatory Factor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

One of the most devastating consequences of diabetes mellitus is a chronic condition, diabetic foot ulcer. Numerous investigations are being targeted to explore newer compounds for treatment of diabetic foot ulcer wounds in diabetic patients. Hesperidin (HSP), an isoflavone glycoside has been established to exhibit antidiabetic and antioxidant potential. In the current investigation, diabetes was induced in rats by administration by streptozotocin (STZ) intraperitoneally (50 mg/kg). Wound-healing capacity was estimated in hind paw of rats by artificially initiating wound injury on the paw dorsal surface. The injured animals were administered with incremental doses of HSP suspension orally (10, 20, 40, 60, and 80 mg/kg) and insulin subcutaneously (10 IU/kg). Parameters such as wound area were estimated every 2 days, and at the end of 20 days of study, biochemical estimations in serum and histopathological observations of the wound were made. HSP (60 and 80 mg/kg) revealed statistically significant ( P < 0.05) improvement in wound dimension, glucose and insulin concentration, and glycated hemoglobin (HbA1C). Administration of HSP indicated significant ( P < 0.05) modulation of mRNA associated with expression of vascular endothelial growth factor (VEGF), whereas the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were lowered compared to the control group of animals. Real-time quantitative polymerase chain reaction (RT-qPCR) indicated expression of vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2) compared to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Histological observations indicated higher expression of VEGF in the groups receiving HSP, indicative of angiogenesis stimulation in the diabetic wound. The results advocate angiogenesis activity of HSP was enhanced owing to reduction in hyperglycemia and oxidative stress–induced damage, reduced expression of inflammatory mediators, and enhanced expression of growth-related factors, thereby promoting healing of diabetic foot ulcer.

scholarly journals Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects

2021 ◽  
Vol 12 ◽  
Author(s):  
Ye Liu ◽  
Yiqiu Liu ◽  
Junyu Deng ◽  
Wei Li ◽  
Xuqiang Nie
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Diabetic Foot ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Diabetic Patients ◽  
Ulcer Formation ◽  
Therapeutic Effects ◽  
Fibroblast Growth

Diabetic foot ulcer (DFU) is a combination of neuropathy and various degrees of peripheral vasculopathy in diabetic patients resulting in lower extremity infection, ulcer formation, and deep-tissue necrosis. The difficulty of wound healing in diabetic patients is caused by a high glucose environment and various biological factors in the patient. The patients’ skin local microenvironment changes and immune chemotactic response dysfunction. Wounds are easy to be damaged and ulcerated repeatedly, but difficult to heal, and eventually develop into chronic ulcers. DFU is a complex biological process in which many cells interact with each other. A variety of growth factors released from wounds are necessary for coordination and promotion of healing. Fibroblast growth factor (FGF) is a family of cell signaling proteins, which can mediate various processes such as angiogenesis, wound healing, metabolic regulation and embryonic development through its specific receptors. FGF can stimulate angiogenesis and proliferation of fibroblasts, and it is a powerful angiogenesis factor. Twenty-three subtypes have been identified and divided into seven subfamilies. Traditional treatments for DFU can only remove necrotic tissue, delay disease progression, and have a limited ability to repair wounds. In recent years, with the increasing understanding of the function of FGF, more and more researchers have been applying FGF-1, FGF-2, FGF-4, FGF-7, FGF-21 and FGF-23 topically to DFU with good therapeutic effects. This review elaborates on the recently developed FGF family members, outlining their mechanisms of action, and describing their potential therapeutics in DFU.

scholarly journals The Effects of Silver-Releasing Foam Dressings on Diabetic Foot Ulcer Healing

2021 ◽  
Vol 10 (7) ◽  
pp. 1495
Author(s):  
Yu-Chi Wang ◽  
Hsiao-Chen Lee ◽  
Chien-Lin Chen ◽  
Ming-Chun Kuo ◽  
Savitha Ramachandran ◽  
...  
Keyword(s):  
Wound Healing ◽  
Diabetic Foot ◽  
Healing Rate ◽  
Early Period ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Wound Management ◽  
Control Group ◽  
Diabetic Patients ◽  
High Morbidity

Diabetic foot ulcers (DFUs) are a serious complication in diabetic patients and lead to high morbidity and mortality. Numerous dressings have been developed to facilitate wound healing of DFUs. This study investigated the wound healing efficacy of silver-releasing foam dressings versus silver-containing cream in managing outpatients with DFUs. Sixty patients with Wagner Grade 1 to 2 DFUs were recruited. The treatment group received silver-releasing foam dressing (Biatain® Ag Non-Adhesive Foam dressing; Coloplast, Humlebaek, Denmark). The control group received 1% silver sulfadiazine (SSD) cream. The ulcer area in the silver foam group was significantly reduced compared with that in the SSD group after four weeks of treatment (silver foam group: 76.43 ± 7.41%, SSD group: 27.00 ± 4.95%, p < 0.001). The weekly wound healing rate in the silver foam group was superior to the SSD group during the first three weeks of treatment (p < 0.05). The silver-releasing foam dressing is more effective than SSD in promoting wound healing of DFUs. The effect is more pronounced in the initial three weeks of the treatment. Thus, silver-releasing foam could be an effective wound dressing for DFUs, mainly in the early period of wound management.

scholarly journals Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

2013 ◽  
Vol 2 (5) ◽  
pp. 195-214 ◽  
Author(s):  
Kenneth W. Finnson ◽  
Sarah McLean ◽  
Gianni M. Di Guglielmo ◽  
Anie Philip
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta
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