Topical application of substance P promotes wound healing in streptozotocin-induced diabetic rats (original) (raw)
Related papers
Topically applied substance P enhanced healing of open excision wound in rats
European Journal of Pharmacology, 2013
Significant social and financial burden due to wounds need newer drugs/formulations to speed up the healing process. Substance P (SP), a neuropeptide, is associated with release of various cytokines and growth factors from inflammatory, epithelial and endothelial cells. In the present study, temporal effects of topically applied SP (10 −7 M in normal saline) were evaluated in the modulation of various cytokines and growth factors that participate in cutaneous wound healing. Gross examination of full thickness open excision wound in rats revealed that once daily topical application of SP significantly increased the wound closure, as compared to control group. SP treatment significantly increased tumor necrosis factorα (TNF-α) and decreased interleukin 10 (IL-10) levels on day 3. On the contrary, on day 7 level of TNF-α decreased and that of IL-10 increased. The mRNA and protein expressions of vascular endothelial growth factor (VEGF) and transforming growth factor-β 1 (TGF-β 1) increased on days 3 and 7, and decreased on day 14 in SP-treated wounds. Histopathological evaluation of hematoxylin and eosin stained wound sections showed that SP treatment produced increased early leukocytes infiltration, fibroblast proliferation, angiogenesis, collagen deposition and re-epithelialization. Results of the present study demonstrate that topical application of SP enhanced wound healing by modulating cytokines, growth factors and cells. Based on the results, it is suggested that SP could be of beneficial use in diabetic wounds where levels of VEGF, TGF-β 1 and SP decrease along with impairment of inflammatory reaction.
Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype
The American Journal of Pathology, 2015
Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. (Am J Pathol 2015, -: 1e11; http:// dx.
Evidence-Based Complementary and Alternative Medicine, 2012
Background and Purpose. This study aimed to evaluate the wound healing activities of Aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. Experimental Approach. Forty-eight Sprague Dawley rats were chosen for this study, divided into 4 groups. Diabetes was induced. Two-centimeter-diameter full-thickness skin excision wounds were created. Animals were topically treated twice daily. Groups 1, the diabetic control group, were treated with 0.2 mL of sterile distilled water. Group 2 served as a reference standard were treated with 0.2 mL of Intrasite gel. Groups 3 and 4 were treated with 0.2 mL of Aftamed and 0.2 mL of chlorine dioxide gels respectively. Granulation tissue was excised on the 10th day and processed for histological and biochemical analysis. The glutathione peroxidase ,superoxide dismutase activities and the malondialdehyde (MDA) levels were determined. Results. Aftamed-treated wounds exhibited significant increases in hydroxyproline, cellular prolife...
Combined effect of substance P and curcumin on cutaneous wound healing in diabetic rats
Journal of Surgical Research, 2017
Background: Our earlier studies demonstrated that topically applied substance P (SP) or curcumin on excision skin wound accelerated the wound healing in streptozotocininduced diabetic rats. In the present study, we aimed to evaluate the wound healing potential of combination of SP and curcumin in diabetic rats. Materials and methods: Open cutaneous excision wound was created on the back of each of the sixty diabetic rats. Wound inflicted rats were equally divided into three groups namely, control, gel-treated and SP + curcumin-treated. Normal saline, pluronic gel and SP (0.5 x 10-6 M) + curcumin (0.15%) were topically applied once daily for 19 days to these control, gel-treated and SP + curcumin groups, respectively. Results: SP + curcumin combination significantly accelerated wound closure and decreased mRNA expressions of tumor necrosis factor-alpha, interleukin-1beta and matrix metalloproteinase-9, whereas the combination markedly increased the expressions of interleukin-10, vascular endothelial growth factor, transforming growth factor-beta1, hypoxia-inducible factor 1-alpha, stromal cell-derived factors-1alpha, heme oxygenase-1 and endothelial nitric oxide synthase and activities of superoxide dismutase, catalase and glutathione peroxidase in granulation/healing tissue, as compared to control and gel-treated groups. In combination group, granulation tissue was better, as was evidenced by improved fibroblast proliferation, collagen deposition, microvessel density, growth associated protein-43 positive nerve fibers and thick regenerated epithelial layer.
Veterinary Medicine: Research and Reports, 2019
Objective: To evaluate the effects of azelnidipine-carboxyl methyl cellulose (AZL-CMC) gel and carboxyl methyl cellulose 2% gel (CMC) on the healing of full-thickness skin wounds of diabetic rats. Methods: Fifteen Sprague Dawley male rats were studied. The rats were divided into three groups: AZL-CMC gel-treated, CMC 2% gel-treated, and control group. Wounds were assessed by wound area measurement every 3 days and histopathology samples were collected at 4, 7 and 12 days post wounding to evaluate the healing process using stereological study. Mann-Whitney U-test repeated measurement and non-parametric one-way analysis of variance (ANOVA) were used to analyze the data using SPSS, version 18. Results: Numerical density of the fibroblasts of the AZL-CMC gel treated group was 59.17 ±2.69 (×10 4 /mm 3) and higher than the control 22.64±1.34 (×10 4 /mm 3) and CMC 2%-treated groups 40.80±5.27 (×10 4 /mm 3), respectively, P<0.001. The volume density of the collagen bundles and LV of the vessels were 83.1±4.46 and 42.16±5.78, respectively, in the AZL-CMC treated group, and higher compared to the control (53.96±5.07, 9.9±2.49) and the CMC 2%-treated (65.88±2.13, 18.1±2.20) groups (P <0.001). Conclusion: The healing of AZL-CMC gel-treated wound was better than the control wounds, grossly. Wound healing processes and wound closure in the intervention group began sooner and was completed more quickly. The quantitative and qualitative parameters showed the significant wound healing effect of the AZL-CMC gel-treated group.
Frontiers in Pharmacology, 2018
Impaired wound healing is considered to be one of the severe complications associated with diabetes. Adelmidrol and trans-traumatic acid are commonly called Nevamast R. This gel consists precisely of 2% adelmidrol and 1% trans-traumatic acid. Thanks to its components, it is capable of favoring the natural process of skin re-epithelialization. This study tests the theory that topical usage of adelmidrol + trans-traumatic acid has important effects on the healing and closure of diabetic wounds in a streptozotocin (STZ)-induced diabetic mouse model. Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg) in 0.01 M citrate buffer (pH 4.5) administrated for 5 consecutive days. After diabetes induction, two longitudinal incisions were made on the dorsum of the mice. The animals were killed between 6 and 12 days from wound induction. We found that diabetic mice compared to control mice presented: a retarded wound closure, characterized by an important reduction in the levels of transforming growth factor-β, plus an important increase of vascular endothelial growth factor and endothelial-type nitric oxide synthase expression, together with a reduction of adhesion molecules such as intercellular adhesion molecule-1 and P-selectin and a prolonged elevation of the levels of matrix metalloproteinase-9 and matrix metalloproteinase-2 in wound tissues. This study demonstrates that topical application of adelmidrol + trans-traumatic acid has important effects on the healing and closure of diabetic wounds in an STZ-induced diabetic mouse model.
Journal of Ethnopharmacology, 2011
Ethnopharmacological relevance: The herbs Radix Astragali (RA) and Radix Rehmanniae (RR) have long been used in traditional Chinese Medicine and serve as the principal herbs in treating diabetic foot ulcer. Aim of study: Diabetic complications, such as foot ulcer, impose major public health burdens worldwide. In our previous clinical studies, two Chinese medicine formulae F1 and F2 have achieved over 80% limb salvage. A simplified 2-herb formula (NF3) comprising of RA and RR in the ratio of 2:1 was used for further study. NF3 was examined for the ulcer healing effect in diabetic rats, and its potential mechanisms of action in fibroblast proliferation, angiogenesis and anti-inflammation in vitro. Materials and methods: A chemically induced diabetic foot ulcer rat model was used for studying the wound healing effect. In the in vitro mechanistic studies, human fibroblast cells (Hs27), human umbilical vein endothelial cells (HUVEC) and mouse macrophage cells (RAW264.7) were assessed for tissue regeneration, angiogenesis and anti-inflammatory activities, respectively. Results: Our in vivo results demonstrated a significant reduction of wound area at day 8 in NF3 (0.98 g/kg) group as compared to control (p < 0.01). NF3 could significantly stimulate Hs27 proliferation in a dose dependent manner (p < 0.05). Besides, NF3 could significantly increase the cell migration and tube formation (p < 0.05-0.001) of HUVEC in the angiogenesis study. Furthermore, significant inhibition of nitric oxide production (p < 0.01) was found in NF3-treated macrophage cells, suggesting its anti-inflammatory activity. Conclusions: Our study presents for the first time scientific evidence towards the efficacy of the twoherb formula NF3 in enhancing diabetic wound healing through the actions of tissue regeneration, angiogenesis and anti-inflammation.
A Detailed Review on Diabetic Wound Healing Activity
Asian journal of pharmaceutical research and development, 2023
Skin damage is known as a wound. Hemostasis, inflammatory, proliferative, and tissue remodelling or resolution are the four perfectly timed and highly planned phases that make up the normal biological process of wound healing in the human body. There are two basic categories of wounds: acute wounds and chronic wounds. Long-term negative effects on one's health are caused by the chronic metabolic condition known as diabetes mellitus, which is becoming more common. 25 percent of those with diabetes mellitus are thought to have poor wound healing due to their diabetes. Oxygenation, infection, hormones related to ageing and sex, stress, diabetes, and obesity, drugs, alcoholism, smoking, and diet are among the factors that affect wound healing. To address their basic medical needs, According to estimates, 80% of people who live in underdeveloped nations need traditional medicines, which are typically made from medicinal plants. Numerous individuals in Africa and other poor nations employ using medicinal herbs to cure diabetic wounds and associated issues due to the abundant supply With therapeutic herbs and enough conventional wisdom regarding wounds healing. Recent developments in functional genomics, nanotechnology, wound healing in diabetics, along with a better knowing the pathophysiology of chronic wounds. In the following review, detailed information about healing of diabetic wounds with mechanism, factors affecting, impairment of wound healing with its pathophysiology, herbal treatments and current advances when treating diabetic wounds are examined.