Effect of nifedipine and amlodipine on wound healing in rats

The wound healing effect of two calcium channel blockers, nifedipine and amlodipine was studied in rats using incision and excision wound models. In incision wound, two straight paravertebral skin thickness incision were made and on tenth day skin tensile strength was measured by using continuous water flow technique. In excision wound, circular piece of skin excised in its full thickness and wound contraction monitored by alternate day wound tracing and epithelisation period was monitored by noting the number of days required for escher to fall. Drugs enhanced the skin tensile strength in incision wound model. In excision wound model, wound contraction is increased on 4th and 16th day but epithlisation period was not significantly altered. In conclusion, calcium channel blockers can be used to enhance wound healing, especially if wound healing was suppressed by steroids.     

Ethosuximide and phenobarbital promote wound healing via enhancing collagenization

The fact that ethosuximide (ETO), phenobarbital (PHO), and barbituric acid (BARB) share structural and pharmacophoric homologies with phenytoin and allantoin, both known to have significant wound‐healing properties, prompted us to evaluate them as wound‐healing agents. Accordingly, ETO‐, PHO‐, and BARB‐containing ointments were applied onto full‐thickness excision and incision wounds created on the dorso‐lumbar region of experimental rats. ETO‐and PHO‐treated incision wounds illustrated significant enhancement in breaking strengths (1380 ± 61 and 1240 ± 42 g, respectively) compared to vehicle controls (1070 ± 18 g) and BARB (1080 ± 45 g). Moreover, biochemical analyses revealed significant increase in hydroxyproline contents in ETO‐ and PHO‐treated wounds compared to vehicle controls. Histological evaluation revealed that both ETO and PHO promoted collagen synthesis and deposition. This is the first time to describe the significant wound‐healing merits of ETO and PHO as potential clinical agents for treatment of chronic wounds.     

Wound healing activity of extracts derived from Shorea robusta resin

Context: Shorea robusta Gaertn.f. (Dipterocarpaceae) resin is used for treating infected wounds and burns by tribals in India.

Objectives: The objective of this study was to investigate wound-healing activity of S. robusta resin extracts and essential oil in rats.

Materials and methods: Methanol extract (SRME), petroleum ether, benzene insoluble fraction of methanol extract (SRPEBIME), and essential oil (SREO) of S. robusta resin were incorporated in soft yellow paraffin (10% w/w) and applied once daily on incision and excision wounds of Wistar rats. Framycetin ointment (1.0% w/w) was applied to the standard group. Tensile strength (on the 10th day), wound contraction, and scar area (on the 14th day) were recorded. On the 15th day, granulation tissues of excision wounds were analyzed for total protein, hydroxyproline, and hexosamine contents and activities of lipid peroxidation and super oxide dismutase (SOD). Histopathology of the wounds was also studied.

Results and discussion: SRPEBIME and SREO healed incision and excision wounds faster than plain ointment base and framycetin. Tensile strength of SRPEBIME-treated incision wounds was 53% higher than that of control animals. In excision wounds, wound contraction and scar areas were found to be 99% and 7.7?mm² (SRPEBIME) and 71.7% and 21?mm² (control). Protein and hydroxyproline contents were higher in SRPEBIME (20.8 and 3.5% w/w) and SREO (17.4 and 2.8% w/w) groups as against 9.95 and 1.48% w/w in control groups. Histopathology revealed complete epithelization and new blood vessel formation in SRPEBIME groups.

Discussion and conclusion: SRPEBIME and SREO have significant wound-healing activities on incision and excision wounds.     

The Stimulatory Effects of Topical Application of Radioactive Lantern Mantle Powder on Wound Healing

Some people in different parts of Iran use burned mantles as a wound healing medicine. To perform surface area measurement, twenty rats were divided randomly into two groups of 10 animals each. The 1st group received topical burned radioactive lantern mantle powder at 1st-3rd day after making excision wounds. The 2nd group received non-radioactive lantern mantle powder. For histological study, 36 male rats randomly divided into two groups of 18 animals each. Full thickness excision wound (314±31.4 mm²) was made on the dorsal neck in all animals after inducing general anesthesia. For the first 3 days, cases received topical application of the radioactive lantern mantle powder. Finally, to measure the tensile strength, an incision was made on the dorsal neck of the rats. Surface area measurement of the wounds showed a progressive surface reduction in both groups. Histological study showed a significant statistically difference between cases and controls with respect to fibrinoid necrosis and neutrophilic exudate at the days 3 and 14. Considering the existence of granulation tissue, a significant difference was observed between case and control groups at days 3 and 7. Tensile strength study showed no significant difference between the cases and controls until 30 days after excision.     

人胎盘提取物对大鼠伤口愈合的作用

AIM: To study wound healing activity of the humanplacental extract(HPE) in rats. METIHODS: Fullthickness wounds were inflicted on depilated dorsum ofCharles foster rats with 8 mm Acu-punch biopsy. TheHPE was applied both at topical and im routes (2.5 mL/kg). Effects were compared on the basis of physicalcriteria, biochemical criteria, and histopathological studywith respect to untreated control, vehicle control (1. 5?nzyl alcohol), and framycetin topical treated groups.RESULTS: Significant lowering of wound size(P<0.05), wound index(P<0.05), and number of daysrequired for complete healing (P<0.01); significantgain in tensile strength(P<0.01); appreciable increaseof tissue DNA, total protein, and collagenesis wereobserved in HPE treated group. CONCLUSION:Human placental extract systematically helps collagenesisleading to potent healing of wounds.     

Enhanced healing efficacy of an optimized gabapentin-melittin nanoconjugate gel-loaded formulation in excised wounds of diabetic rats

The present study aimed to design and optimize, a nanoconjugate of gabapentin (GPN)-melittin (MLT) and to evaluate its healing activity in rat diabetic wounds. To explore the wound healing potency of GPN-MLT nanoconjugate, an in vivo study was carried out. Diabetic rats were subjected to excision wounds and received daily topical treatment with conventional formulations of GPN, MLT, GPN-MLT nanoconjugate and a marketed formula. The outcome of the in vivo study showed an expedited wound contraction in GPN-MLT-treated animals. This was confirmed histologically. The nanoconjugate formula exhibited antioxidant activities as evidenced by preventing malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic exhaustion. Further, the nanoconjugate showed superior anti-inflammatory activity as it inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). This is in addition to enhancement of proliferation as indicated by increased expression of transforming growth factor-β (TGF- β), vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor receptor-β (PDGFRB). Also, nanoconjugate enhanced hydroxyproline concentration and mRNA expression of collagen type 1 alpha 1 (Col 1A1). In conclusion, a GPN-MLT nanoconjugate was optimized with respect to particle size. Analysis of pharmacokinetic attributes showed the mean particle size of optimized nanoconjugate as 156.9 nm. The nanoconjugate exhibited potent wound healing activities in diabetic rats. This, at least partly, involve enhanced antioxidant, anti-inflammatory, proliferative and pro-collagen activities. This may help to develop novel formulae that could accelerate wound healing in diabetes.     

Evaluation of Antimicrobial and Wound Healing Potentials of Ethanol Extract of Wedelia biflora Linn D.C. Leaves

To rationalize scientifically the traditional claim on use of Wedelia biflora (Linn.) D. C. for the treatment of wounds and infections, the present study was designed to evaluate the antimicrobial and wound healing activity of ethanol extract of leaves of W. biflora. In in vitro assays the test extract was subjected to antimicrobial activity by agar well-diffusion method and minimum inhibitory concentration method in different microbial strains. Wound healing activity of the test extract was studied by excision wound model and incision wound model in Wistar albino rats. In excision wound model, 97.90% wound healing was recorded in 10% w/w extract treated group on 16^th days of postsurgery, whereas only 58.50% was observed in control group. In incision model, higher breaking strength, high hydroxyl proline content and histopathological study in extract treated groups revealed higher collagen redeposition than the control group. The agar well-diffusion evaluation and minimum inhibitory concentration established antimicrobial efficacy of ethanol extracts of W. biflora. These observations established the traditional claim and therapeutic activity of W. biflora and it could be a potent wound healing candidate for use in future.     

Evaluation of Wound Healing Potential of Bauhinia purpurea Leaf Extracts in Rats

The present study was carried out to evaluate the effect of methanol and chloroform extracts of Bauhinia purpurea on experimentally induced excision, incision, burn and dead space wound models in Sprague Dawley rats. Formulations of methanol and chloroform extracts of Bauhinia purpurea were prepared in carbopol and simple ointment base at concentrations of 2.5% and 5% and applied to the wounds. In the excision and burn wound models, animals treated with high doses of methanol and chloroform showed significant reduction in time taken for epithelization and wound contraction (50%) compared to control. A significant increase in breaking strength was found in incision wound model with methanol and chloroform extracts compared to their respective bases. In the dead space wound model, methanol and chloroform extract treatment (100 and 500 mg/kg) orally produced a significant increase in the breaking strength, dry tissue weight and hydroxyproline content of the granulation tissue when compared to control. Among the extracts, methanol extract exhibited more activity followed by the chloroform extract. In conclusion, the present study indicated that Bauhinia purpurea leaves exhibited wound healing activity.     

The effects of topical (gel) astemizole and terfenadine on wound healing

Objective:

To develop topical gel preparations of astemizole and terfenadine and to investigate the actions of the gels on the healing of incision and excision wounds in male albino rats.

Materials and Methods:

Gels containing 1% astemizole, with varying concentrations of carbopol 934 (polymer), were prepared. Similarly, 1% terfenadine gels were made. The formulations were evaluated for release rate and stability. Incision and excision wounds were inflicted on male albino rats under ketamine anesthesia, taking aseptic precautions. The animals were divided into two groups. They were given a topical application of either astemizole or terfenadine gel, at a dose of 100 mg per wound, once daily, for 10 days in the case of incision wounds and till the time of complete closure in the case of excision wounds. On the 11^th day, breaking strength of the incision wound was measured. In the excision wound model, wound closure rate, epithelization time, scar features and hydroxyproline content of scar tissue were studied from the day of wounding till the day of the scab falling off, with no residual raw area.

Results:

Gels prepared using 0.8% carbopol 934 and 1% of drug in gel base were found to be stable. The gels of astemizole and terfenadine significantly (P < 0.05) promoted the phases of healing such as collagenation (in incision wounds), wound contraction and epithelization (in excision wounds).

Conclusion:

The gels of astemizole and terfenadine might play an important role in wound management program.     

枯草芽孢杆菌活菌制剂促进创伤皮肤愈合的实验研究

目的：探讨枯草芽孢杆菌活菌制剂对创伤皮肤愈合的影响。方法：以大鼠后背全层皮肤切除创伤愈合过程为模型，局部外用枯草芽孢杆菌活菌制剂并设对照，制作病理组织切片，测定创面羟脯氨酸含量变化，同时测量创面愈合面积，记录愈合时间。结果：应用枯草牙孢杆菌活菌制剂可促进成纤维细胞增生，提高胶原含量，创面愈合时间较对照组明显缩短。结论：枯草牙孢杆菌活菌制剂具有促进创伤皮肤愈合的作用。     

Influence of ethanolic extract of Jasminum grandflorum linn flower on wound healing activity in rats

The influence of flower extract of Jasminum grandiflorum was studied for its wound healing activity at a dose of 250 mg/kg body weight, using excision and dead space wound models in rats. The animals were divided into three groups in excision wound model, the controls (n=10) were treated with 0.25% CM cellulose, reference standard (n=10) were treated with sulfathiazole ointment and the experimental (n=10) were treated with extract of J. grandiflorum flower till complete epithelialization. The animals in dead space wound models were divided into two groups, controls were given plain drinking water and the experimental animals were administered with extract orally for 10 days. The extract treated wounds were found to epithelize faster as compared to controls. Extract-treated rats exhibited 65% reduction in the wound area when compared to controls (54%). The wet and dry granulation tissue weight, and hydroxyproline content in a dead space wound model increased significantly (P < 0.001) when compared to controls. Histological studies of the tissue obtained on day 10 from the extract-treated group showed increased well organized bands of collagen, more fibroblasts and few inflammatory cells when compared to controls which showed inflammatory cells, scanty collagen fibres and fibroblasts. The. demonstration of increased rate of wound contraction together with the biochemical and histological findings suggest the use of J. grandiflorum flower extract in the management of wound healing.     

Effect of aged garlic extract on wound healing: A new frontier in wound management

Successful wound healing depends upon angiogenesis, and impaired angiogenesis is a hallmark of the chronic wounds encountered with diabetes and venous or arterial insufficiency. To intervene and improve wound closure, it is essential to investigate the effects of different natural remedies in wound healing. The chicken dorsum skin excisional wound assay was used to investigate the influence of different concentrations of aged garlic solution (AGS) on wound healing. Gross, histopathology, scanning electron microscopy (SEM) and computer-based three-dimensional (3D) image-probing techniques were utilized to determine the effects of AGS on wound closure, re-epithelialization, dermal matrix regeneration, and angiogenesis. Ninety chicks, aged 1 week and divided in 6 groups, were topically exposed to different concentrations of AGS for 6 days: control (group A), 1% (group B), 5% (group C), 10% (group D), 15% (group E), and skin lotion (group F). Different patterns, ranging from incomplete to almost complete wound closure, were observed among different groups with highly significant results (P?<?0.001) in group E. Histological investigations revealed a positive augment in the re-epithelialization of all AGS exposed wounds. An increase in the number of new loosely packed collagen and maturation of collagen bundles was observed in all treated wounds at days 4 and 6 post-wounding, respectively. Similar results were achieved through SEM of treated wounds. Histological investigations revealed the profuse dose-dependent neovascularization among AGS-treated wounds. Abbott curve, angular spectrum, and different parameters of 3D surface roughness of wounds were also measured for the precise quantification of angiogenesis. A very highly significant (P?<?0.001) increase in angiogenesis was observed among all treated groups. No significant change was observed among control and skin lotion–treated groups. These observations substantiate the beneficial use of AGS in the treatment of wounds. Additional studies are needed to study the specific wound-healing mechanisms of chemical, or group of chemicals, present in AGS.     

Wound healing activity of Ocimum sanctum Linn with supportive role of antioxidant enzymes

The present study was performed to evaluate the wound healing and antioxidant effect of aqueous extract of Ocimum sanctum Linn. (O. sanctum) in rats. Albino rats of either sex were divided into 2 groups. Group I: Wounded control rats; Group II: Wounded rats administered O. sanctum aqueous extract. Wound breaking strength in incision wound model, epithelization period and percent wound contraction in excision wound model were studied. Using dead space wound model, granulation tissue breaking strength, granulation tissue dry weight, hydoxyproline level in dry granulation tissue, superoxide dismutase (SOD) and catalase levels in wet granulation tissue were estimated in both the groups. Increased wound breaking strength, decreased epithelization period, increased percent wound contraction, increased granulation tissue weight and hydroxyproline concentrations were observed. The increased activity of antioxidant enzymes such as SOD, catalase level in extract treated group compared to controls. Granulation tissue was subjected to histopathological examination to determine the pattern of lay-down for collagen using Haematoxylin and Eosin stains which confirm the results. Owing to wound healing and antioxidant activities, O. sanctum may be useful in the management of abnormal healing such as keloids and hypertrophic scars.     

Effects of Epidermal Growth Factor Dosage Forms on Mice Full-thickness Skin Wound Zinc Levels and Relation to Wound Strength

Epidermal growth factor (EGF) and zinc promote re-epithelization and reparative tissue strength by enhancing deposition of collagen at the site of the wound. In this study two EGF dosage forms were chosen to assess the effect of zinc levels on wound healing and for comparison with wound tear strengths. A solution of EGF in 0.9% w/v NaCl and an EGF gel in 0.2% Carbopol 940 polymer (5 μL) were applied to full-thickness skin wounds of mice twice a day for 7 and 15 days. Wound zinc levels were higher on day 7 than on day 15, especially in wounds treated with EGF. The wound zinc levels of the gel + EGF group on day 15 were similar to those of normal control skin. These results imply that there is a close connection, but no direct relationship, between EGF application in both dosage forms and wound zinc levels during healing.     

Wound healing activity of alcoholic extract of Kaempferia galanga in Wistar rats

The wound healing effect of alcoholic extract of Kaempferia galanga (K. galanga) and its effect in dexamethasone suppressed wound healing was studied in Wistar rats. Three wound models viz. incision, excision and dead space wounds were used in this study. The parameters studied were breaking strength in case of incision wounds, epithelialization and wound contraction in case of excision wound and granulation tissue dry weight, breaking strength and hydroxyproline content in case of dead space wound. The dexamethasone treated group showed a significant (P < 0.001) reduction in the wound breaking strength when compared to control group in incision type of wound model. Coadministration of K. galanga with dexamethasone had significantly (P < 0.001) increased the breaking strength of dexamethasone treated group. In excision wound model, the percentage of the wound contraction was significantly (P < 0.05) increased by K. galanga only on 16th day and also it reversed the dexamethasone suppressed wound contraction on the 16 day. K. galanga significantly (P < 0.001) reduced the time required for epithelialization and reversed the epithelialization delaying effect of dexamethasone significantly (P < 0.001).     

The effects of histamine liberators and exogenous histamine on wound healing in rat.

The effects of compound 48/80, adenosine-5-triphosphate (ATP) and exogenous histamine (Hi) on the healing of excised surface wound and tensile strength of surgical skin wound in rat were studied. The chemicals were injected directly into the wound area. 48/80, ATP and exogenous Hi were found to stimulate the wound healing as measured by collagen formation, tensile strength examination and a measurement of the surface circular wound. When given separately, the order of activities was: 48/80 is greater than ATP is greater than Hi; when administered together as a mixture, compound 48/80, ATP and exogenous Hi also accelerated the wound healing. The mixture shortened the healing process by about 5 days as compared with 17 days in control.     

Xanthinol nicotinate and wound healing

In an experimental study the local effect of i.v. applied xantinol-nicotinate (Complamin) on healing skin incisions in rats was studied. In conclusion, there was a higher ultimate tensile strength of wounds treated by the agent, based on the increased synthesis of collagen fibres. This statement was proved by the alteration of free hydroxyproline in serum. Histologically, there was an intensive vascularization of the wound healing area. Concerning the elastic behaviour we found a more rigid regenerative tissue in the early phases of healing on account of the enhanced thickness of the wound area.     

Pharmaceutical application of frog skin on full-thickness skin wound healing in mice

Abstract

Context: It has been proved that fresh frog skin is efficient in the wound healing process.

Objective: The purpose of study is to introduce a formulation of frog skin powder for evaluation of wound repair where fresh frog skin is not available.

Materials and methods: Rana ridibunda (Ranidae) skins were lyophilized, and a powder was prepared. The powder (0.0005?g) was then mixed with ointment (0.0065?g) for treating each wound. Formulation was used on full-thickness wounds on mice (FO group) and compared to positive and negative controls. In order to study the wound healing process, wound contraction, inflammation, number of fibroblast cells, neovascularization and collagen density were evaluated on days 2, 4 and 6 following the injury. Moreover, CFU measurement was performed for the evaluation of wound contamination.

Results: Acceleration in wound contraction in the FO group compared to control groups was significant (p?<?0.001) on days 4 and 6. Results showed that FO treatment considerably decreased inflammatory cells during the study. On day 4, FO treatment was significantly effective in increasing the number of fibroblast cells and collagen density (p?<?0.01 and p?<?0.05, respectively). On day 6 the number of fibroblast cells (p?<?0.001), collagen density (p?<?0.05) and neovascularization (p?<?0.05), were higher in the FO group than the control groups. Results of CFU measurement demonstrated significant reduction of wound contamination in FO treated wounds on days 2 (p?<?0.05) and 4 (p?<?0.01).

Discussion and conclusion: Our findings indicated that the pharmaceutical form of frog skin used in this study has considerable healing and antibacterial effects on wounds.     

Anti-inflammatory and antioxidant properties of unripe papaya extract in an excision wound model

Abstract

Context: Carica papaya L. (Caricaceae) fruit was shown to exhibit wound healing properties.

Objectives: We investigated anti-inflammatory and antioxidant potential of papaya fruit phosphate-buffered saline extract (PE) during wound healing and enhancement of the potentials due to trace ions addition.

Materials and methods: Rat excision wounds were topically treated twice/day with 20?µL of PE (5?mg extract/mL), 0.5?µg Se²⁺ added PE (PES), or 100?µM Zn²⁺ added PE (PEZ). Control groups were treated with deionized water (negative) and deproteinized calf blood extract ointment (Solcoseryl®, positive). Lipid peroxidation (LPX), antioxidant, proinflammatory, and arginine metabolic enzymes were estimated in the wound excised on days 4 and 10 post wounding.

Results: PE (5?mg/mL; 9.80?±?0.33?d) and PES (PE?+?0.5?µg Se²⁺; 8.90?±?0.23?d) significantly (p?<?0.05) reduced the average time for complete wound closure compared with the negative (13.00?±?0.37?d) and positive (9.80?±?0.33?d) controls, respectively. Biochemical evaluations of LPX product (malondialdehyde), antioxidant (catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx)), and pro-inflammatory (cyclooxygenase-2 and myeloperoxidase (MPO)) enzyme activities and metabolites (nitrite and urea), on days 4 and 10 post wounding, confirmed the anti-inflammatory and antioxidant properties of PE and PES in this study.

Discussion and conclusion: Treatment of excision wounds with papaya extract, especially with the addition of selenium for 10?d, reduced inflammation associated oxidative damage apparently via cyclooxygenase specific inhibition, arginine metabolism, and up-regulation of antioxidant enzymes.