Wound Healing In Diabetic Rats Research Articles

Acceleration of Wound Healing in Diabetic Rats through a Novel 3D Organo-Hydrogel Nanocomposite of Polydopamine/TiO2 Nanoparticles and Cu (PDA-TiO2@Cu).

Diabetic wound represents a serious issue with a substantial impact and an exceptionally complex pathology affecting patients' mental health and quality of life. So, we have developed a novel 3D organo-hydrogel nanocomposite of polydopamine/TiO2 nanoparticles and cu (PDA-TiO2@Cu) and examined its efficacy in diabetic wound healing. Forty-five adult male albino rats were divided into normal control rats (non-diabetic rats with non-treated skin wounds), diabetic control rats (diabetic rats with non-treated skin wounds), and organo-hydrogel-treated rats (diabetic wounds treated with topically applied organo- hydrogel once daily). Macroscopic changes of the wound were observed on days 0, 3, 5, 7, and 10 to measure wound diameters. Skin specimens from the wound tissue were taken on days 3, 7, and 10, respectively, and examined histologically and immunohistochemically. Also, the gene expressions of collagen I, Matrix Metalloproteinase-9 (MMP-9), and Epidermal Growth Factor (EGF), and levels of Interleukin 6 (IL-6) and Superoxide Dismutase (SOD) were assessed. Our observed results indicated that the developed patch significantly accelerated the healing time compared to the normal control and diabetic control groups. Moreover, the patchloaded group revealed complete re-epithelization and a highly significant increase in the mean area % of CD31 immunostaining on day 7. The organo-hydrogel-loaded group displayed a significant decrease in gene expression of MMP-9 and a significant increase in gene expression of EGF and collagen I. Additionally, the organo-hydrogel-loaded group exhibited a significant decrease in levels of IL-6 and a significant increase in levels of SOD, compared to the normal diabetic control groups. The organo-hydrogel can be used for treating and decreasing the healing period of diabetic wounds.

Boosting wound healing in diabetic rats: The role of nicotinamide riboside and resveratrol in UPR modulation and pyroptosis inhibition

BackgroundDiabetes-related skin ulcers provide a substantial therapeutic issue, sometimes leading to amputation, needing immediate practical treatments for efficient wound care. While the exact mechanisms are unknown, pyroptosis and deregulation of the unfolded protein response (UPR) are known to exacerbate inflammation. Nicotinamide Riboside (NR) and Resveratrol (RV), which are known for their Nicotinamide adenine dinucleotide (NAD+) boosting and anti-inflammatory properties, are being studied as potential treatments. The purpose of this study was to shed light on the underlying molecular mechanisms and explore the medical application of NR and RV in diabetic wound healing. Methods54 male Sprague-Dawley rats divided into control, diabetic (DM), Gel Base, DM-NR, DM-RV, and DM-NR + RV. Rats were orally administered 50 mg/kg/day of RV and 300 mg/kg/day of NR for 5 weeks. Following diabetes induction, their wounds were topically treated with 5 % NR and RV gel for 15 days. The wound closure rate, body weight, and serum lipid profiles were examined. Gene expression study evaluated UPR and pyroptosis-related genes (BIP, PERK, ATF6, IRE1α, sXBP1, CHOP, NLRP3, caspase-1, NFκB, and IL1-β) in wound tissues, alongside histological assessment of cellular changes. ResultsNR and RV treatments greatly enhanced wound healing. Molecular investigation demonstrated UPR and pyroptosis marker modifications, suggesting UPR balance and anti-inflammatory effects. Histological investigation demonstrated decreased inflammation and increased re-epithelialization. The combination of NR and RV therapy had better results than either treatment alone. ConclusionThis study shows that NR and RV have therapeutic promise in treating diabetic wounds by addressing UPR dysregulation, and pyroptosis. The combination therapy is a viable strategy to improving the healing process, providing a multimodal intervention for diabetic skin ulcers. These findings pave the way for additional investigation and possible therapeutic applications, giving hope for better outcomes in diabetic wound care.

Photobiomodulation preconditioned diabetic adipose derived stem cells with additional photobiomodulation: an additive approach for enhanced wound healing in diabetic rats with a delayed healing wound.

In this preclinical investigation, we examined the effects of combining preconditioned diabetic adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation (PBM) on a model of infected ischemic delayed healing wound (injury), (IIDHWM) in rats with type I diabetes (TIDM). During the stages of wound healing, we examined multiple elements such as stereology, macrophage polarization, and the mRNA expression levels of stromal cell-derived factor (SDF)-1α, vascular endothelial growth factor (VEGF), hypoxia-induced factor 1α (HIF-1α), and basic fibroblast growth factor (bFGF) to evaluate proliferation and inflammation. The rats were grouped into: (1) control group; (2) diabetic-stem cells were transversed into the injury site; (3) diabetic-stem cells were transversed into the injury site then the injury site exposed to PBM; (4) diabetic stem cells were preconditioned with PBM and implanted into the wound; (5) diabetic stem cells were preconditioned with PBM and transferred into the injury site, then the injury site exposed additional PBM. While on both days 4, and 8, there were advanced histological consequences in groups 2-5 than in group 1, we found better results in groups 3-5 than in group 2 (p < 0.05). M1 macrophages in groups 2-5 were lower than in group 1, while groups 3-5 were reduced than in group 2 (p < 0.01). M2 macrophages in groups 2-5 were greater than in group 1, and groups 3-5 were greater than in group 2. (p ≤ 0.001). Groups 2-5 revealed greater expression levels of bFGF, VEGF, SDF- 1α, and HIF- 1α genes than in group 1 (p < 0.001). Overall group 5 had the best results for histology (p < 0.05), and macrophage polarization (p < 0.001). AD-MSC, PBM, and AD-MSC + PBM treatments all enhanced the proliferative stage of injury repairing in the IIDHWM in TIDM rats. While AD-MSC + PBM was well than the single use of AD-MSC or PBM, the best results were achieved with PBM preconditioned AD-MSC, plus additional PBM of the injury.

Lactobacillus Plantarum Promotes Wound Healing by Inhibiting the NLRP3 Inflammasome and Pyroptosis Activation in Diabetic Foot Wounds.

Diabetic foot ulcer (DFU) impairs the quality of life of diabetic patients and overburdens healthcare systems and society. It is crucial to comprehend the pathophysiology of DFU and develop effective treatment strategies. The aim of this study was to to evaluate the therapeutic potential of Lactobacillus Plantarum (LP) on wound healing in DFU and to explore the underlying mechanisms. To investigate the effects of LP on wound healing, human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs) and used to assess cell viability, migration, and pyroptosis using CCK-8, cell scratch, and flow cytometry. The levels of IL-1β and IL-18 were measured by ELISA. The expression of NLRP3, caspase-1 p20, and GSDMD-N was detected by Western blot. Additionally, NLRP3 inhibitor MCC950 was used to treat a diabetic rat model established by streptozotocin (STZ). Pearson correlation analysis was performed to analyze the relationship between LP and NLRP3, IL-1β, IL-18 in ulcer tissue. Our data mechanistically demonstrate that AGEs activate the NLRP3/Caspase-1/GSDMD pathway, leading to an increase in the levels of IL-1β and IL-18 and ultimately promoting cell pyroptosis. Furthermore, we identified that LP inhibits the effects of AGEs by downregulating NLRP3 inflammasome activity. LP facilitated wound healing in diabetic rats and resulted in decreased protein levels of NLRP3 and its downstream target caspase-1 p20. Finally, we observed a negative correlation between LP and NLRP3, IL-1β, IL-18 in diabetic foot skin tissue. Our findings uncovered a novel role of LP in diabetic foot wound healing via regulation of the NLRP3 inflammasome, suggesting this link as a therapeutic target. In future research, it would be valuable to explore the signaling cascades involved in LP-mediated inhibition of NLRP3 inflammasome activation.

Mentha piperita silver nanoparticle-loaded hydrocolloid film for enhanced diabetic wound healing in rats.

To investigate the role of Mentha piperita silver nanoparticle-loaded carbopol gel for enhanced wound healing in a diabetic rat model. This research further aims to explore bioactive compounds derived from Mentha piperita obtained from high altitude. Methanolic extracts of Mentha piperita (MP), Mentha spicata (MS) and Mentha longifolia (ML) were used to synthesise silver nanoparticles (AgNP). AgNP synthesis was confirmed by ultraviolet-visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The antioxidant activity was assessed by 2, 2-diphenyl-1-picrylhydrazyl (DDPH) assay. Antiglycation potential was determined by measuring the fluorescent advanced glycation end products. The bioactive compound identified in the Mentha piperita methanolic (MPM) fraction through electrospray ionisation tandem mass spectrometric analysis (ESI-MS) was responsible for the highest antiglycation. The effects of MPM and MPM.AgNP-loaded Carbopol (Sanare Lab, India) on wound healing were compared in male, alloxan-induced, diabetic albino rats (200-250g), divided into control and treated groups. Effects on wound healing were assessed via histopathology. UV-Vis and FTIR confirmed NP synthesis with peaks for flavonoids and polyphenols. SEM and XRD explored the cubical, 30-63nm crystalline NP. The maximum antioxidant and antiglycation potential was observed in order of; MP.AgNP>MS.AgNP>ML.AgNP. The highest antioxidant activity was observed by methanolic and aqueous MP.AgNPs (88.55% and 83.63%, respectively) at 2mg.ml-1, and (75.16% and 69.73%, respectively) at 1mg.ml-1, compared to ascorbic acid (acting as a positive control, 90.01%). MPM.AgNPs demonstrated the best antiglycation potential of 75.2% and 83.3% at 1mg.ml-1 and 2mg.ml-1, respectively, comparable to positive control (rutin: 88.1%) at 14 days post-incubation. A similar trend was observed for antimicrobial activity against Bacillus subtilis, Micrococcus luteus and Escherichia coli with an inhibition zone of 21mm, 21.6mm and 24.6mm. Rosmarinic acid was the active compound present in Mentha piperita, as identified by ESI-MS. MPM.AgNP-loaded Carbopol resulted in 100% wound closure compared with control at 20 days post-wounding. In the treatment group, re-epithelialisation was achieved by day 18, compared with 25 days for the positive control group. MPM.AgNP-loaded Carbopol demonstrated safer and more effective biological properties, hence accelerating the diabetic excision wound healing process in alloxan-induced diabetic rats.

Formulation and Evaluation of Topical Delivery Diosgenin Emulgel for Diabetic Wounds

A variety of cellular processes work together in a highly coordinated manner to facilitate a complex and dynamic process of wound healing ensuring the efficient restoration of injured tissue. Diosgenin, a plant sterol saponin is primarily found in various plants. The aim of this research was to create an emulgel containing Diosgenin and examine its effects on wound healing in diabetic rats with excision wounds. Histopathological findings further supported the efficacy of the emulgel and results indicate that the application of Diosgenin Emulgel (DE) shows an effective approach for healing of diabetic wounds. The objective of the research stands to explore the possibility of formulation development and wound-healing capabilities of DE. The study evaluated the wound healing effects of the DE in Streptozotocin-induced (STZ) (55 mg/kg) given by intraperitoneal route diabetes and control group. The emulgel was topically applied to assess its effectiveness in promoting wound healing. The application of DE on the rat wounds resulted in a notable wound closure within a 21-day period and significant epithelization was observed with p &lt; 0.001. The study concluded that the formulation demonstrated remarkable effectiveness in promoting the functional recovery of diabetic wounds.

Dang-Gui-Bu-Xue decoction improves wound healing in diabetic rats by the activation of Notch signaling

Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.

The effect of geraniol dressing obtained from rose oil wound healing in diabetic rats

Introduction: Diabetic foot is one of the most important chronic complications of diabetes mellitus. In this study, the aim was to investigate the healing effect of dressing with geraniol material obtained from rose oil. Materials and Methods: The experimental period of the study was carried out between June 2, 2016, and 27, 2016. Sprague-Dawley rats were used and three experimental, two control groups were formed. In the study conducted with a total of 40 rats, each group consisted of eight rats. Geraniol dressing, isotonic wet dressing, and hydrocolloid wound dressing were applied topically once a day to the first, second, and third groups, respectively. No dressing was applied to the positive and negative control groups. Index of oxidative stress of wound healing was assessed by total antioxidant status/total oxidant status measurements. Results: Due to the macroscopic results, it was determined that wound score was significantly decreased on day 3 in the first group and non-diabetic groups compared with other groups. When the microscopic findings were compared with day 0, in the first group, significant decrease of the level of collagen density and epithelization was observed on day 10. In the first group, increase in fat cells had become significant than other groups. In the CD34, SMA and vimentin staining, the first group showed superiority to other dressings. In the last measurements, the highest drop was seen in geraniol dressed and negative control groups. Conclusion: According to the study, geraniol dressed group provided similar wound healing with negative control group and showed superiority to the other products used as a standard in wound care.

RETRACTED: Alhakamy et al. Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment. Pharmaceutics 2022, 14, 1133.

The journal retracts the article, "Fluoxetine Ecofriendly Nanoemulsion Enhances Wound Healing in Diabetic Rats: In Vivo Efficacy Assessment" [...].

Engineered keratin/bFGF hydrogel to promote diabetic wound healing in rats

Keratin materials are promising in wound healing acceleration, however, it is a challenge for the keratin to efficiently therapy the impaired wound healing, such as diabetic foot ulcers. Here, we report a keratin/bFGF hydrogel for skin repair of chronic wounds in diabetic rats based on their characteristics of extracellular matrix and growth factor degradation in diabetic ulcer. Recombinant keratin 31 (K31), the most abundant keratin in human hair, exhibited the highly efficient performances in cell adhesion, proliferation and migration. More importantly, the introduction of bFGF into K31 hydrogel significantly enhances the properties of cell proliferation, wound closure acceleration, angiogenesis and skin appendages regeneration. Furthermore, the combination of K31 and bFGF can promote epithelial-mesenchymal transition by inhibiting the expression of E-cadherin and promoting the expression of vimentin and fibronectin. These findings demonstrate the engineered K31/bFGF hydrogel as a promising therapeutic agent for diabetic wound healing.

RETRACTED: Asfour et al. Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats. Pharmaceutics 2022, 14, 1792.

Pharmaceutics retracted the article "Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats" [...].

Porous Collagen Sponge Loaded with Large Efficacy-Potentiated Exosome-Mimicking Nanovesicles for Diabetic Skin Wound Healing.

Diabetic skin wounds are difficult to heal quickly due to insufficient angiogenesis and prolonged inflammation, which is an urgent clinical problem. To address this clinical problem, it becomes imperative to develop a dressing that can promote revascularization and reduce inflammation during diabetic skin healing. Herein, a multifunctional collagen dressing (CTM) was constructed by loading large efficacy-potentiated exosome-mimicking nanovesicles (L-Meseomes) into a porous collagen sponge with transglutaminase (TGase). L-Meseomes were constructed in previous research with the function of promoting cell proliferation, migration, and angiogenesis and inhibiting inflammation. CTM has a three-dimensional porous network structure with good biocompatibility, swelling properties, and degradability and could release L-Meseome slowly. In vitro experiments showed that CTM could promote the proliferation of fibroblasts and the polarization of macrophages to the anti-inflammatory phenotype. For in vivo experiments, on the 21st day after surgery, the wound healing rates of the control and CTM were 83.026 ± 4.17% and 93.12 ± 2.16%, respectively; the epidermal maturation and dermal differentiation scores in CTM were approximately four times that of the control group, and the skin epidermal thickness of the CTM group was approximately 20 μm, which was closest to that of normal rats. CTM could significantly improve wound healing in diabetic rats by promoting anti-inflammation, angiogenesis, epidermal recovery, and dermal collagen deposition. In summary, the multifunctional collagen dressing CTM could significantly promote the healing of diabetic skin wounds, which provides a new strategy for diabetic wound healing in the clinic.

Macrophage plasticity enhanced by camel milk peptide attributes in wound healing in diabetic rats

Diabetes Mellitus during wound healing alters macrophage recruitment, leading to delayed healing. The present study focuses on impact of camel milk peptide (CMP) on macrophage plasticity during their recruitment during wound healing stages. The Swiss albino rats were distributed into three groups: a normal wounded group (control), a wounded diabetic group, and a wounded diabetic group treated with CMP daily. The diabetic rats showed a significantly compromised level of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein (MIP-1α) relative gene expression, anti-CD31, anti-Mac-3, and anti-CD68 staining than the control group. Macrophages were considerably depleted in diabetic group animals upon initiating the inflammatory phase, while the protein significantly reversed the same. Also, there was marked increase in pathogenic bacterial growth at the wound sites of diabetic rats. On the contrary, in CMP-diabetic rats, levels of pathogenic bacteria were comparable to normal control animals. Diabetic rats demonstrated a reduction in matrix metalloproteinase (MMP-9 and MMP-13) expression while increased TNF-α levels compared to control rats. In addition, they also showed significantly reduced expression of VEGF and fibroblast growth factors (FGF) genes and IL-10 during the proliferation phase. However, all these parameters exhibited a considerably reversed trend in the CMP treated diabetic rats. Hence, CMP-treated diabetic rats demonstrated a transition to the M2 phenotype, highlighting macrophage recruitment's critical role in healing of wounds in hyperglycemic rats.

Evaluation of the Clinical Effect of Hyaluronic Acid Mouthwash on Palatal Secondary Wound Healing in Diabetic Rats

Objective: The objective of this study was to investigate clinical effect of topically administered hyaluronic acid (HA) mouthwash on healing of secondary palatal wound in diabetic (D) rats. &#x0D; Methods: 60 Wistar albino male rats were divided into D and non-diabetic (ND) groups. Diabetes was induced to 30 randomly selected rats by initially administering 110 mg/kg of nicotinamide intraperitoneally, followed by 15 min of intraperitoneal injection of 65 mg/kg of streptozotocin solution. 5 mm excisional wounds were made in the centre of the palate. After that, 6 animals from each group were sacrificed. Then, both groups were subdivided into two groups: 0.12% HA mouthwash and saline (S) (n=12 per group), depending on the agent to be administered to the wound area (WA). On days 7 and 14, six rats from each group were sacrificed, and the WAs were measured through photographic measurements utilizing Image J software.&#x0D; Results: The WA decreased with time in each group (p

Gynura divaricata (L.) DC. promotes diabetic wound healing by activating Nrf2 signaling in diabetic rats

The ethnopharmacological significanceDiabetic chronic foot ulcers pose a significant therapeutic challenge as a result of the oxidative stress caused by hyperglycemia. Which impairs angiogenesis and delays wound healing, potentially leading to amputation. Gynura divaricata (L.) DC. (GD), a traditional Chinese herbal medicine with hypoglycemic effects, has been proposed as a potential therapeutic agent for diabetic wound healing. However, the underlying mechanisms of its effects remain unclear. Aim of the studyIn this study, we aimed to reveal the effect and potential mechanisms of GD on accelerating diabetic wound healing in vitro and in vivo. Materials and methodsThe effects of GD on cell proliferation, apoptosis, reactive oxygen species (ROS) production, migration, mitochondrial membrane potential (MMP), and potential molecular mechanisms were investigated in high glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) using CCK-8, flow cytometry assay, wound healing assay, immunofluorescence, DCFH-DA staining, JC-1 staining, and Western blot. Full-thickness skin defects were created in STZ-induced diabetic rats, and wound healing rate was tracked by photographing them every day. HE staining, immunohistochemistry, and Western blot were employed to investigate the effect and molecular mechanism of GD on wound healing in diabetic rats. ResultsGD significantly improved HUVEC survival, decreased apoptosis, lowered ROS production, restored MMP, improved migration ability, and raised VEGF expression. The use of Nrf2-siRNA completely abrogated these effects. Topical application of GD promoted angiogenesis and granulation tissue growth, resulting in faster healing of diabetic wounds. The expression of VEGF, CD31, and VEGFR was elevated in the skin tissue of diabetic rats after GD treatment, which upregulated HO-1, NQO-1, and Bcl-2 expression while downregulating Bax expression via activation of the Nrf2 signaling pathway. ConclusionThe findings of this study indicate that GD has the potential to serve as a viable alternative treatment for diabetic wounds. This potential arises from its ability to mitigate the negative effects of oxidative stress on angiogenesis, which is regulated by the Nrf2 signaling pathway. The results of our study offer valuable insights into the therapeutic efficacy of GD in the treatment of diabetic wounds, emphasizing the significance of directing interventions towards the Nrf2 signaling pathway to mitigate oxidative stress and facilitate the process of angiogenesis.

Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.

Retracted: Astragalus Polysaccharides Promote Wound Healing in Diabetic Rats by Upregulating PETN and Inhibiting the mTOR Pathway

Retracted: Astragalus Polysaccharides Promote Wound Healing in Diabetic Rats by Upregulating PETN and Inhibiting the mTOR Pathway

Effect of Combination of Some Phytoconstituents of Pharmacological Interest on Cutaneous Wound Healing in Diabetic Rats

Persistent non-healing wounds present a substantial challenge in the context of diabetes management. This research delves into exploring the wound healing capabilities of a combination of natural plant-derived compounds, namely embelin, berberine, ferulic acid, and asiatic acid, in streptozotocin induced diabetic rats. Various wound models, including dead space, incision, and excision models, were employed to evaluate their impact. The phytoconstituents were carefully blended into an ointment formulation, with a concentration of 5% (w/w), specifically designed to cater to their individual strengths. Notably, diabetic rats exhibited a significant enhancement in wound closure and improved skin epithelialization. Furthermore, this combination of phytoconstituents exhibited efficacy when administered orally in both the incision and dead space wound models. In the incision wound model, granulation tissues were examined on the 8th day following the initial injury, and assessments were made for hydroxyproline, hexosamine, total protein. In streptozotocin-induced diabetic rats, both topical and oral applications of this combination revealed a marked increase in hydroxyproline, hexosamine, indicating a favorable impact on wound healing. Additionally, the combination led to a substantial improvement in wound breaking strength. When assessed in the dead space model, the combination notably increased the weight and breaking strength of granuloma tissue. These findings collectively point to the wound healing acceleration attributed to Combination in diabetic rats.

Ozonated saline intradermal injection: promising therapy for accelerated cutaneous wound healing in diabetic rats.

The use of ozonized water is gaining importance in medicine due to its effects on hyperglycemia and wound healing mechanisms. This experiment was conducted to assess the impacts of intradermal administration of ozonated water on acute skin wound healing in a diabetic rat model. Sixty-four adult male Wistar rats were randomly divided into two groups: an ozonated water group (O3W) and a control group (CG). Experimental diabetes was chemically induced in the rats by the intraperitoneal administration of 60 mg/kg streptozotocin. One week later, full-thickness skin surgical wounds (1 cm2) were created between the two shoulders of the rats under general anesthesia. The wounds were then daily irrigated with normal saline (CG) or intradermally injected with 1 mL of ozonated water at 10 mg/L O3W. Wound healing was evaluated through macroscopic analysis, measuring wound size, diameter, and percentage of contraction rate before wounding and at 3, 7, 9, 12, 14, 18, 21, 24, and 28 days post-wounding. On days 7, 14, 21, and 28 after induction of the wounds, the body weights and blood glucose levels of rats (8 per group) were measured before the rats were euthanized. Moreover, the morphological structure of the tissue, vascular endothelial and transforming growth factor (VEGF and TGF) affinity and gene expression were examined. The O3W group had significantly lower blood glucose levels and wound size and gained body weight. Additionally, epithelial vascularization, stromal edema, TGF, and VEGF gene expression significantly improved in the O3W group. Therefore, ozonated water has the potential to enhance and promote cutaneous wound healing in diabetic rats.

Effect of hydroalcoholic extract of Trigonella foenum-graecum leaves on wound healing in type 1 diabetic rats.

Diabetes describes a group of metabolic disorders characterised by increased blood glucose concentration. People living with diabetes have a higher risk of morbidity and mortality than the general population. In 2015 it was estimated that there were 415 million (uncertainty interval: 340-536 million) people with diabetes aged 20-79 years, and 5.0 million deaths attributable to diabetes. When diabetic patients develop an ulcer, they become at high risk for major complications, including infection and amputation. The pathophysiologic relationship between diabetes and impaired healing is complex. Vascular, neuropathic, immune function, and biochemical abnormalities each contribute to the altered tissue repair. The use of herbal medicine has increased and attracted the attention of many researchers all over the world. In this study, we have evaluated the effect of 500mg/kg hydroalcoholic extract of Trigonella foenum-graecum leaves (TFG-E) on wound healing in diabetic rats using a full-thickness cutaneous incisional wound model. Wounds of treated animals showed better tensiometric indices, accelerated wound contraction, faster re-epithelialisation, improved neovascularisation, better modulation of fibroblasts and macrophage presence in the wound bed and moderate collagen formation.