Topical Administration of an Ointment Prepared From Satureja sahendica Essential Oil Accelerated Infected Full-Thickness Wound Healing by Modulating Inflammatory Response in a Mouse Model

2021 ◽  
Vol 33 (12) ◽  
pp. 321-328
Author(s):  
Khaled Omarizadeh ◽  
Mohammad Reza Farahpour ◽  
Mahshid Alipour
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Essential Oil ◽  
Cellular Proliferation ◽  
Transforming Growth Factor ◽  
Topical Administration ◽  
Control Group ◽  
Collagen Biosynthesis ◽  
Full Thickness ◽  
Infected Wound

Introduction. Satureja sahendica has antibacterial and anti-inflammatory properties that can have beneficial effects for decreasing inflammation in infected wounds. Objective. This study was conducted to evaluate the effects of an ointment prepared from S sahendica essential oil (SSO) on an infected wound model in BALB/c mice. Materials and Methods. One full-thickness excisional skin wound was surgically created per animal and inoculated with 5 × 107 colony-forming units of Pseudomonas aeruginosa and Staphylococcus aureus. Following induction of the wound, the mice (N = 90) were treated with soft yellow paraffin (negative control, n = 18), mupirocin (positive control, n = 18) and 1%, 2%, and 4% SSO (n = 18 in each of the 3 groups). To determine the effect of the treatments on healing of an infected wound, the following factors were assessed: rate of the wound area, tissue bacterial count, histopathology, collagen biosynthesis, immunohistochemistry, and the expressions of insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-4, transforming growth factor beta (TGF-ß), and chemokine (CXC motif) ligand 1 (CXCL-1) on days 3, 7, and 14 after induction of the wound. Results. Topical administration of SSO shortened the inflammatory phase, accelerated cellular proliferation, and increased fibroblast distribution per 1 mm2, collagen deposition, and rapid reepithelialization in comparison with control animals (P <.05). The messenger RNA levels of IGF-1, IL-10, FGF-2, VEGF, TGF-ß1, and CXCL-1 were remarkably increased, and IL-1ß level decreased (P <.05) in the treated animals compared with the control group (P <.05). The immunohistochemical analyses showed topical administration of SSO increased collagen biosynthesis in the treated group (P <.05). Conclusions. Topical administration of SSO shows evidence of accelerating wound healing by upregulating the expression of IGF-1, IL-10, FGF-2, VEGF, TGF-ß, and CXCL-1; shortening the inflammatory stage; and promoting the proliferative phase.

scholarly journals Collagen extract obtained from Nile tilapia (Oreochromis niloticus L.) skin accelerates wound healing in rat model via up regulating VEGF, bFGF, and α-SMA genes expression

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Zizy I. Elbialy ◽  
Ayman Atiba ◽  
Aml Abdelnaby ◽  
Ibrahim I. Al-Hawary ◽  
Ahmed Elsheshtawy ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Rat Model ◽  
Nile Tilapia ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Control Group ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Genes Expression

Abstract Background Collagen is the most abundant structural protein in the mammalian connective tissue and represents approximately 30% of animal protein. The current study evaluated the potential capacity of collagen extract derived from Nile tilapia skin in improving the cutaneous wound healing in rats and investigated the underlying possible mechanisms. A rat model was used, and the experimental design included a control group (CG) and the tilapia collagen treated group (TCG). Full-thickness wounds were conducted on the back of all the rats under general anesthesia, then the tilapia collagen extract was applied topically on the wound area of TCG. Wound areas of the two experimental groups were measured on days 0, 3, 6, 9, 12, and 15 post-wounding. The stages of the wound granulation tissues were detected by histopathologic examination and the expression of vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-ß1) were investigated using immunohistochemistry. Moreover, relative gene expression analysis of transforming growth factor-beta (TGF-ß1), basic fibroblast growth factor (bFGF), and alpha-smooth muscle actin (α-SMA) were quantified by real-time qPCR. Results The histopathological assessment showed noticeable signs of skin healing in TCG compared to CG. Immunohistochemistry results revealed remarkable enhancement in the expression levels of VEGF and TGF-β1 in TCG. Furthermore, TCG exhibited marked upregulation in the VEGF, bFGF, and α-SMA genes expression. These findings suggested that the topical application of Nile tilapia collagen extract can promote the cutaneous wound healing process in rats, which could be attributed to its stimulating effect on recruiting and activating macrophages to produce chemotactic growth factors, fibroblast proliferation, and angiogenesis. Conclusions The collagen extract could, therefore, be a potential biomaterial for cutaneous wound healing therapeutics.

scholarly journals A novel mechanism in maggot debridement therapy: protease in excretion/secretion promotes hepatocyte growth factor production

2011 ◽  
Vol 301 (6) ◽  
pp. C1423-C1430 ◽  
Author(s):  
Kenjiro Honda ◽  
Koji Okamoto ◽  
Yasuhiro Mochida ◽  
Kunihiro Ishioka ◽  
Machiko Oka ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Transforming Growth Factor ◽  
Femoral Vein ◽  
Transforming Growth Factor Β1 ◽  
Control Group ◽  
Drug Target Discovery ◽  
Maggot Debridement Therapy ◽  
Hepatocyte Growth

Maggot debridement therapy (MDT) is effective for treating intractable wounds, but its precise molecular mechanism, including the association between MDT and growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.8 yr, 5 male and 4 female) with intractable wounds of lower extremities because they did not respond to conventional therapies. Significant increases of hepatocyte growth factor (HGF) levels were observed in femoral vein blood during 48 h of MDT ( P < 0.05), but no significant change was found for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1), or tumor necrosis factor-α (TNF-α). We conducted NIH-3T3 cell stimulation assay to evaluate the relation between HGF and protease activity in excretion/secretion (ES) derived from maggots. Compared with the control group, HGF was significantly higher in the 0.05 μg/ml ES group ( P < 0.01). Furthermore, protease inhibitors suppressed the increase of HGF ( P < 0.05). The HGF expression was increased in proportion to the ES protein concentration of 0.025 to 0.5 μg/ml. In fact, ES showed stronger capability of promoting HGF production and less cytotoxicity than chymotrypsin or bromelain. HGF is an important factor involved in cutaneous wound healing. Therefore, these results suggest that formation of healthy granulation tissue observed during MDT results from the increased HGF. Further investigation to identify molecules enhancing HGF expression by MDT will contribute greatly to drug target discovery for intractable wound healing therapy.

scholarly journals Increased Growth Factors Play a Role in Wound Healing Promoted by Noninvasive Oxygen-Ozone Therapy in Diabetic Patients with Foot Ulcers

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jing Zhang ◽  
Meiping Guan ◽  
Cuihua Xie ◽  
Xiangrong Luo ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Standard Therapy ◽  
Transforming Growth Factor ◽  
Ozone Treatment ◽  
Foot Ulcers ◽  
Control Group ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Ozone Therapy

Management of diabetic foot ulcers (DFUs) is a great challenge for clinicians. Although the oxygen-ozone treatment improves the diabetic outcome, there are few clinical trials to verify the efficacy and illuminate the underlying mechanisms of oxygen-ozone treatment on DFUs. In the present study, a total of 50 type 2 diabetic patients complicated with DFUs, Wagner stage 2~4, were randomized into control group treated by standard therapy only and ozone group treated by standard therapy plus oxygen-ozone treatment. The therapeutic effects were graded into 4 levels from grade 0 (no change) to grade 3 (wound healing). The wound sizes were measured at baseline and day 20, respectively. Tissue biopsies were performed at baseline and day 11. The expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β(TGF-β), and platelet-derived growth factor (PDGF) proteins in the pathologic specimens were determined by immunohistochemical examinations. The effective rate of ozone group was significantly higher than that of control group (92% versus 64%,P<0.05). The wound size reduction was significantly more in ozone group than in control group (P<0.001). After treatment, the expressions of VEGF, TGF-β, and PDGF proteins at day 11 were significantly higher in ozone group than in control group. Ozone therapy promotes the wound healing of DFUs via potential induction of VEGF, TGF-β, and PDGF at early stage of the treatment. (Clinical trial registry number isChiCTR-TRC-14004415).

scholarly journals Wound Healing Effects of Prunus yedoensis Matsumura Bark in Scalded Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jin-Ho Lee ◽  
Kyungjin Lee ◽  
Mi-Hwa Lee ◽  
Bumjung Kim ◽  
Khanita Suman Chinannai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Tissue Regeneration ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Control Group ◽  
Sprague Dawley ◽  
Tissue Proliferation ◽  
Inflammatory Phase ◽  
Prunus Yedoensis

Pruni Cortex has been used to treat asthma, measles, cough, urticaria, pruritus, and dermatitis in traditional Korean medicine. The objective of this study was to investigate the effects of Prunus yedoensis Matsumura bark methanol extract (PYE) on scald-induced dorsal skin wounds in rats. Scalds were produced in Sprague-Dawley rats with 100°C water and treated with 5% and 20% PYE (using Vaseline as a base), silver sulfadiazine (SSD), and Vaseline once a day for 21 days, beginning 24 hours after scald by treatment group allocation. The PYE-treated groups showed accelerated healing from 12 days after scald, demonstrated by rapid eschar exfoliation compared to the control and SSD groups. PYE-treated groups showed higher wound contraction rates and better tissue regeneration in comparison with the control group. Serum analysis showed that transforming growth factor beta 1 and vascular endothelial growth factor levels remained high or gradually increased up to day 14 in both PYE groups and then showed a sharp decline by day 21, implying successful completion of the inflammatory phase and initiation of tissue regeneration. These findings suggested that PYE is effective in promoting scald wound healing in the inflammation and tissue proliferation stages.

scholarly journals Application of pomegranate (Punica granatum Linn.) fruit extract for accelerating post-tooth extraction wound healing

2018 ◽  
Vol 51 (4) ◽  
pp. 189
Author(s):  
Intan Nirwana
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Treatment Group ◽  
Tooth Extraction ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Punica Granatum ◽  
Control Group ◽  
Wound Healing Process ◽  
Significant Difference

Background: Trauma occurring during tooth extraction can cause complications such as bleeding, infection, fracture and dry socket and constitutes an inflammatory response trigger. Pomegranate (Punica granatum Linn.) extract, which contains large amounts of punicallagin and ellagic acid, possesses various qualities, including; anti-inflammatory, anti-bacterial and anti-oxidant. Pomegranate extract can inhibit proinflammatory cytokine production, while also suppressing inflammation response thereby accelerating wound healing. Purpose: This study aimed to analyze the effect of pomegranate extract application to the tooth extraction wounds of Cavia cobaya (C. cobaya) on the expression of fibroblast growth factor-2 (FGF-2) and transforming growth factor β (TGF-β) on the fourth day of the wound-healing process. Methods: This study used 12 C. cobaya, divided into two groups, namely; control and treatment. The subjects were anesthetized, before their lower left central incisor was extracted and the entire socket filled with CMC-Na 3% in members of the control group and pomegranate extract in those of the treatment group. The twelve C. cobaya were sacrificed on day 4, their lower jaw subsequently being removed and decalcified for approximately 30 days. The mandibula tissue was stained using a immunohistochemical technique. FGF-2 and TGF-β were used to evaluate the healing process in the extracted tooth socket. Differences in the expression of FGF-2 and TGF-β were evaluated statistically by means of a t-test. Results: This study indicated a significant difference between the control and the treatment groups (p<0.05). The treatment group members whose sockets were filled with pomegranate extract showed high FGF-2 and TGF-β expression. Conclusion: This study confirmed that the administration of pomegranate extract to post-extraction tooth wounds of C. cobaya increases the expression of FGF-2 and TGF-β on day 4, thereby accelerating the wound healing process.

scholarly journals Ceftriaxone and Melittin Synergistically Promote Wound Healing in Diabetic Rats

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1622
Author(s):  
Nabil A. Alhakamy ◽  
Giuseppe Caruso ◽  
Basma G. Eid ◽  
Usama A. Fahmy ◽  
Osama A. A. Ahmed ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Hydroxypropyl Methylcellulose ◽  
Ion Pairing ◽  
Diabetic Rats ◽  
Control Group ◽  
Diabetic Patients ◽  
Type I ◽  
Tgf Β1

High glucose levels in diabetic patients are implicated in delay wound healing that could lead to more serious clinical complications. The aim of the present work was to examine the formulation of ceftriaxone (CTX) and melittin (MEL) as nanoconjugate (nanocomplex)-loaded hydroxypropyl methylcellulose (HPMC) (1.5% w/v)-based hydrogel for healing of acute wounds in diabetic rats. The CTX–MEL nanoconjugate, formulated by ion-pairing at different molar ratio, was characterized for size and zeta potential and investigated by transmission electron microscopy. CTX–MEL nanoconjugate was prepared, and its preclinical efficacy evaluated in an in vivo model of acute wound. In particular, the potential ability of the innovative CTX–MEL formulation to modulate wound closure, oxidative status, inflammatory markers, and hydroxyproline was evaluated by ELISA, while the histopathological examination was obtained by using hematoxylin and eosin or Masson’s trichrome staining techniques. Quantitative real-time PCR (qRT-PCR) of the excised tissue to measure collagen, type I, alpha 1 (Col1A1) expression and immunohistochemical assessment of vascular endothelial growth factor A (VEGF-A) and transforming growth factor beta 1 (TGF-β1) were also carried out to shed some light on the mechanism of wound healing. Our results show that the CTX–MEL nanocomplex has enhanced ability to regenerate epithelium, also giving better keratinization, epidermal proliferation, and granulation tissue formation, compared to MEL, CTX, or positive control. The nanocomplex also significantly ameliorated the antioxidant status by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) levels. The treatment of wounded skin with the CTX–MEL nanocomplex also showed a significant reduction in interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) pro-inflammatory cytokines combined with a substantial increase in hydroxyproline, VEFG-A, and TGF-β1 protein expression compared to individual components or negative control group. Additionally, the CTX–MEL nanocomplex showed a significant increase in mRNA expression levels of Col1A1 as compared to individual compounds. In conclusion, the ion-pairing nanocomplex of CTX–MEL represents a promising carrier that can be topically applied to improve wound healing.

scholarly journals Nocardia rubra cell wall skeleton accelerates cutaneous wound healing by enhancing macrophage activation and angiogenesis

2018 ◽  
Vol 46 (6) ◽  
pp. 2398-2409 ◽  
Author(s):  
Yi Wang ◽  
Ying Hu ◽  
Ben Ma ◽  
Fei Wang ◽  
Sheng Liu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Wall ◽  
Transforming Growth Factor ◽  
Wound Dressings ◽  
Control Group ◽  
Cutaneous Wound Healing ◽  
Full Thickness ◽  
Cutaneous Wound ◽  
Expression Levels ◽  
Tgf Β1

Objective This study was performed to investigate the effect of Nocardia rubra cell wall skeleton (N-CWS) on wound healing of full-thickness skin defects. Methods Two 2- × 2-cm full-thickness wounds, one on each side of the midline, were made on the back of 12 rats. One wound was covered with Vaseline gauze soaked in normal saline, whereas the other was covered with Vaseline gauze and N-CWS. Wound dressings were changed every other day from day 0 (wound creation) to day 11. Four of the 12 rats were killed on day 7, and biopsy samples were obtained for biochemical and histopathological analyses. The expression levels of CD31, CD68, and F4/80 in the tissues were examined immunohistologically. The expression of transforming growth factor (TGF)-β1 in the wound was determined by western blot. Results N-CWS increased the wound healing rate, reduced the complete wound healing time, and increased the expression levels of CD31, CD68, and F4/80 on day 7. The TGF-β1 expression level in the wound was significantly higher in the N-CWS group than in the control group on day 7. Conclusions N-CWS can activate macrophages, increase TGF-β1 expression, and enhance angiogenesis and thus accelerate cutaneous wound healing.

Effects of Avotermin (Transforming Growth Factor β3) in a Clinically Relevant Pig Model of Long, Full-Thickness Incisional Wounds

2010 ◽  
Vol 14 (5) ◽  
pp. 223-232 ◽  
Author(s):  
Hugh G. Laverty ◽  
Nick L. Occleston ◽  
Mark Johnson ◽  
John Little ◽  
Richard Jones ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Clinical Parameters ◽  
Full Thickness ◽  
Relevant Model ◽  
Normal Wound Healing ◽  
Surgical Incisions ◽  
Dermal Wound

Background: The pig is an accepted species for evaluating the safety of molecules in dermal wound healing indications; however, the sizes of wounds assessed have not always been comparable to large incisions encountered clinically. Objective: To develop a clinically relevant model of incisional wounding in the Göttingen minipig for assessing the safety and tolerance of compounds in development to improve scarring. Methods: Intradermal avotermin (recombinant transforming growth factor β3 [TGFβ3]) up to 6,000 ng/100μL was administered twice to 20 cm full-thickness incisions. Results: Incisions were well tolerated in the minipig. Avotermin treatment was not associated with adverse changes in a range of clinical parameters, including wound healing and strength. Plasma TGFβ3 levels were transient with ≈0.1% bioavailability. Conclusion: A clinically relevant model of long, full-thickness, sutured surgical incisions in the minipig is achievable. Avotermin is well tolerated in this model and does not adversely affect normal wound healing at levels that significantly exceed those doses to be used clinically in humans.

scholarly journals Evaluation of the Wound Healing Potential ofResina Draconis (Dracaena cochinchinensis)in Animal Models

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Huihui Liu ◽  
Shaohui Lin ◽  
Dan Xiao ◽  
Xiao Zheng ◽  
Yan Gu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Histopathological Examination ◽  
Wound Contraction ◽  
Control Group ◽  
Traditional Use ◽  
Dragon’S Blood ◽  
Group I ◽  
Resina Draconis

Resina Draconis(RD) is a type of dragon's blood resin obtained fromDracaena cochinchinensis(Lour.) S.C. Chen (Yunnan, China). It has been used as a medicine since ancient times by many cultures. The ethanolic extract ofResina Draconis(RDEE) was evaluated for its wound-healing activity using excision and incision wound models in rats. Group I, the control group, was treated with ointment base. Group II, which served as a reference standard, was treated with moist exposed burn ointment (MEBO). Group III was treated with RDEE. The parameters observed were percentage of wound contraction, epithelialization period, tensile strength, histopathological studies, microvessel density (MVD), and the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). The group treated with RDEE showed significantly better wound contraction and better skin-breaking strength as compared with the control group. The results of histopathological examination, MVD, and the expression levels of growth factors supported the outcome of the wound models as well. The present study provided a scientific rationale for the traditional use of RD in the management of wounds.

Effects of Transforming Growth Factor-Beta 2, Interleukin 6 and Fibronectin on Corneal Epithelial Wound Healing

1998 ◽  
Vol 8 (4) ◽  
pp. 224-229 ◽  
Author(s):  
H. Er ◽  
E. Uzmez
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Control Group ◽  
Corneal Epithelial ◽  
Treatment Groups ◽  
Epithelial Wound Healing ◽  
Growth Factor Beta ◽  
Beta 2

Purpose The aim of this study was to compare the effects of topically applied transforming growth factor-beta 2 (TGF-beta 2) and interleukin 6 (IL-6), alone and combined with fibronectin, on the rate of corneal wound healing in rabbits. Methods Twenty-eight rabbits were used for the experiment. After the right eye of each rabbit was debrided with n-heptyl alcohol, the animals were divided into four treatment groups (six rabbits per group) and one control group (four rabbits). The debrided eyes were treated, beginning immediately after wounding and continuing every 2 hours from 8 a.m. to 8 p.m. for 48 hours. Group 1 received TGF-beta 2; group 2 IL-6; group 3, TFR-beta 2 and purified fibronectin; group 4, IL-6 and fibronectin; control group, balanced salt solution. At set intervals each eye was stained with fluorescein and photographed; epithelial defects were measured with a computer-assisted digitizer. The healing rate was calculated by linear regression analysis. Results The mean healing rates in groups 1, 2, 3, 4, and controls were respectively 1.65 ± 0.16, 1.68 ± 0.11, 1.99 ± 0.12, 2.23 ± 0.09, and 0.93 ± 0.18 mm2/h. Mean epithelial healing rates for all drug-treatment groups were significantly faster than controls. The healing rates of groups 3 and 4 were significantly faster than groups 1 and 2. Conclusions We conclude that cytokines, in combination with extracellular matrix proteins, facilitate corneal epithelial wound healing in vivo, possibly by making corneal epithelial cells more sensitive to fibronectin receptors.

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