Effect of histamine on wound healing.

Using incision, excision and dead space wound models in rats, a study was conducted on the effect of histamine on wound healing. Exogenous histamine given either ip or locally was without any effect. Semicarbazide as (histamine synthesis inhibitor) suppressed healing process (breaking strength of skin incision wound), decreased breaking strength and hydroxyproline content of granulation tissue and delay in period of epithelization. On the other hand compound 48/80 (a promoter of histamine forming capacity) was found to promote wound healing. Exogenous histamine (topical) reversed the anti-healing effect of semicarbazide on incision and excision wounds.     

Wound healing potential of Solanum xanthocarpum in streptozotocin‐induced diabetic rats

Objectives

The objective of the present study was to evaluate wound healing potential of Solanum xanthocarpum extract in streptozotocin‐induced diabetic rats.

Methods

Alcoholic extract of the aerial parts (ESX ) was subjected to phytochemical estimations and its standardization with chlorogenic acid using HPLC . ESX was then evaluated for wound healing potential in, streptozotocin‐induced diabetic rats using excision and incision wound models on topical and oral treatment Various biochemical evaluations, such as collagen, hexosamine, hyaluronic acid, protein, DNA along with antioxidant parameters, proinflammatory cytokines, VEGF and histopathological examination were also evaluated.

Key findings

Extract of S. xanthocarpum depicted the presence of mainly alkaloids, polyphenols, steroids, while content of chlorogenic acid was found to be 8.44% w/w. The maximum effective nature of ESX in healing was observed at 10% gel (topical) and 200 mg/kg (orally) in diabetic rats, where highest healing power was observed when treated both orally and topically. Biochemical evaluations showed significant increase in the levels of collagen, hexosamine, hyaluronic acid, protein, DNA followed by significant decline in the levels of blood glucose, lipid peroxidation, nitric oxide and expression of proinflammatory cytokines, supported by histopathology.

Conclusions

The potential healing effect in diabetic rats may be attributed to the presence of chlorogenic acid in combination with other phytoconstituents.

     

Wound healing activity of Withania coagulans in streptozotocin-induced diabetic rats

Context: Withania coagulans Dunal. (Solanaceae) has been shown to possess hypoglycemic, free radical scavenging and wound healing activity. Therefore, it may be worthwhile to study the effect of Withania coagulans in diabetic wound healing.

Objective: This study included determination of rate of wound contraction and estimation of various biochemical parameters such as collagen, hexosamine, total protein, total DNA, SOD and CAT levels in the granulation tissues.

Materials and methods: The hydroalcoholic fraction of the methanolic extract (standardized by withaferin-A using high performance thin layer chromatography (HPTLC) )of Withania coagulans in the form of 10% w/w ointment topically and at a dose of 500?mg/kg per oral (p.o.) was administered to streptozotocin-induced diabetic rats. The results obtained were compared with diabetic control and Aloe barbadensis Miller (syn. Aloe vera L.) (Liliaceae) was used as a reference drug.

Results: The amount of withaferin-A present in the methanolic extract was 3.67?mg/g of the extract. The hydroalcoholic fraction in both the forms, i.e., topical (10% w/w ointment) and oral (500?mg/kg, p.o.) showed a significant increase in the rate of wound contraction (83.02% topical and 65.14% oral) topical and 93.18% oral) when compared to diabetic control (66which was further justified with significant increase in the levels of collagen, protein, DNA, SOD, CAT, and decreased level of hexosamine.

Discussion and conclusion: The hydroalcoholic fraction of Withania coagulans in oral form is found to be more effective than the topical form. However, further studies are in progress to find the lead molecules responsible for the wound healing effect.     

Wound healing activity of the ethanol root extract and polyphenolic rich fraction from Potentilla fulgens

Context: Potentilla fulgens Wall. ex Hook (Rosaceae) is a potent medicinal plant of the Western Himalayas, where its roots are traditionally used by the local people of Uttaranchal (India) to treat wounds and tiger bites.

Objective: The present study scientifically evaluates the wound healing activity of P. fulgens ethanol root extract (EPF) and its ethyl acetate fraction (PFEA) on experimental rats.

Materials and methods: Wounds were inflicted on animals by using both excision and incision models. The wounded animals were treated for 16 days with EPF (oral: 200–400?mg/kg and topical: 5–10% w/w) and PFEA (oral: 75?mg/kg; topical: 1.75% w/w). Various physical (wound contraction, epithelialization rate, tensile strength) and biochemical parameters (hydroxyproline, hexosamine, proteins, DNA) were examined during the study. Oxidant product (lipidperoxidase), antioxidant enzymes (catalase, superoxide-dismutase) and reduced glutathione were determined. Morphological and histopathological studies of the skin tissues were monitored.

Results: A significant (p?<?0.05) wound healing property was observed when the animals were treated topically with EPF (10% w/w) and PFEA (1.75% w/w). A significantly (p?<?0.05) increased in the levels of hydroxyproline, hexosamine, protein and DNA up to 59.22, 70.42, 61.01 and 60.00% was observed, respectively. This effect was further demonstrated by the morphological and histopathological representation, thus showing significant (p?<?0.05) re-epethelialization on the healing area. EPF and PFEA also showed significant (p?<?0.05) antioxidant activity.

Conclusions: The present study provided the scientific evidence, where P. fulgens rich in polyphenolic components possess remarkable wound healing activities, thereby supporting the traditional claims.     

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.     

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).     

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.     

Wound healing properties of Indian propolis studied on excision wound-induced rats

Context: In traditional medicine propolis is widely used for the treatment of various ailments including ulcer and wound healing. The phytochemical screening of Indian propolis indicates the presence of biologically active ingredients in appreciable amounts. In the absence of systematic evaluation of wound healing properties of Indian propolis in the literature, the present study was undertaken.

Objective: The aim of this study was to evaluate the wound healing potential of Indian propolis on excision wounds induced in experimental rats.

Materials and methods: Excision wounds were created in male Wistar rats and were treated with Indian propolis ointment (nitrofurazone was used as a reference drug - widely used for wound healing) for a period of 14 days. Control rats were treated with petroleum jelly. The parameters analyzed include wound contraction, hydroxyproline, hexosamine, uronic acid, total protein, DNA, and RNA.

Results: Topical application of propolis ointment for 14 days significantly improved the wound contraction when compared to the control group of rats. The determination of hydroxyproline, hexosamine, uronic acid, DNA, RNA and protein levels in the wound matrix revealed the pro-healing effects of propolis. The results obtained were comparable with nitrofurazone.

Discussion and conclusion: It appears that the ethanol extract of Indian propolis possesses significant pro-healing activity by accelerating the healing process at various phases of tissue repair. The presence of biologically active ingredients such as flavonoids, phenolic acids, terpenes, benzoic acids, amino acids and vitamins, etc. in Indian propolis may readily account for the observed prophylactic action of propolis in wound healing.     

Molecular docking of glycogen synthase kinase3-β inhibitor oleanolic acid and its wound-healing activity in rats

Glycogen Synthase Kinase3-β (GSK3-β) is involved in energy metabolism, cell development, and body pattern formation, whose inhibition promotes wound healing through β-catanin-dependent Wnt signaling pathway. Molecular Docking of oleanolic acid isolated from Methanolic extract of Grewia tiliaefolia bark to GSK3-β was studied by Wnt signaling pathway. The activation domain of GSK3-β docked with oleanolic acid showed the inhibition constant 1.55 × 10^?9 whereas, standard drug sulphathiazole showed inhibition constant of 9.27 × 10^?6. Both extract and isolated constituent were studied for their potency using excision, incision, and dead space wound models in rats. In oleanolic acid-treated animals (1 % w/w ointment cream base), epithelialization was faster with 96.82 % wound contraction on 16th post wounding day. Tensile strength of incision wound was significantly increased to 580.832.95 g after intraperitoneal administration of oleanolic acid (12 mg kg^?1 body weight). In dead space wound, a significant increase in weight, tensile strength, hydroxyproline content and increased collagenation of granuloma tissue was observed. Further in silico findings hypothesized that oleanolic acid may exert the healing activity by inhibiting GSK3-β through β-catanin-dependent Wnt signaling pathway.     

Safety and healing efficacy of Sea buckthorn (Hippophae rhamnoides L.) seed oil on burn wounds in rats

The present investigation was undertaken to determine the safety and efficacy of supercritical CO₂-extracted Hippophae rhamnoides L. (Sea buckthorn) (SBT) seed oil on burn wound model. SBT seed oil was co-administered by two routes at a dose of 2.5 ml/kg body weight (p.o.) and 200 μl (topical) for 7 days on experimental burn wounds in rats. The SBT seed oil augmented the wound healing process as indicated by significant increase in wound contraction, hydroxyproline, hexosamine, DNA and total protein contents in comparison to control and reference control treated with silver sulfadiazine (SS) ointment. Histopathological findings further confirmed the healing potential of SBT seed oil. SBT seed oil treatment up-regulated the expression of matrix metalloproteinases (MMP-2 and 9), collagen type-III and VEGF in granulation tissue. It was observed that SBT seed oil also possesses antioxidant properties as evidenced by significant increase in reduced glutathione (GSH) level and reduced production of reactive oxygen species (ROS) in wound granulation tissue. In acute and sub-acute oral toxicity studies, no adverse effects were observed in any of the groups administered with SBT seed oil. These results suggest that the supercritical CO₂-extracted Sea buckthorn seed oil possesses significant wound healing activity and have no associated toxicity or side effects.     

Effect of phenytoin sodium on macrophages in rat wounds

本实验旨在研究苯妥英钠（ＰＳ）对伤口巨噬细胞（Ｍ）的影响．从置入大鼠背部伤口的聚乙烯醇海绵中收集巨噬细胞，分别测定其吞噬功能，肿瘤坏死因子α（ＴＮＦα）和白介素１（ＩＬ－１）的释放以及对成纤维细胞增殖调节作用，通过牵拉伤口组织致其断裂时溢出的水的重量而测定伤口牵张强度．结果表明，伤口Ｍ的功能在伤后ｄ５达到高峰，ＰＳ１，１０，５０ｇ·Ｌ－１浓度依赖性地增加伤后ｄ５的伤口Ｍ的数量，吞噬功能，ＴＮＦα和ＩＬ－１的释放，增强Ｍ对成纤维细胞增殖的刺激作用，增强伤口牵张强度．结果说明ＰＳ加速伤口愈合，与其增强Ｍ的功能有关．     

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.     

Evaluation of wound healing activity of henna,pomegranate and myrrh herbal ointment blend

This study assessed the wound healing potential and antimicrobial activity of henna, pomegranate and myrrh extract formulations and their blend in excision, and dead space wound models in rats in comparison to a marketed ointment (gentamycin). The natural extracts were used in ointment formulations alone or in a combination of three extracts at a total concentration of 15% w/w in medications. The percent of wound contraction in case of henna, myrrh, pomegranate, the blend and gentamycin (10?mg/kg) were 85.90–98.5%, 88.35–99.52%, 93.55–100%, 97.30–100%, and 90.25–100% from days 16 to 20, respectively. The blended formulation showed the highest increase in the percent of wound contraction and decrease in the epithelisation period compared to other formulations and showed comparable results to the standard ointment. The histological studies of excision biopsy at day 24 showed healed skin structures with normal epithelisation, the restoration of adnexa and fibrosis within the dermis in all of the formulation- and gentamycin-treated groups while the control group lagged behind in the formation of the amount of ground substance in the granulation tissue. The formulations showed antimicrobial activity against Candida, Staphylococcus aureus, mucous membrane infections and E. coli topical infections. The study proved the wound healing potential and antimicrobial activity of the herbal extract.     

Evaluation of wound healing potential of Calotropis gigantea latex studied on excision wounds in experimental rats

The present study was aimed at evaluating the wound healing potential of Calotropis gigantea latex on excision wound induced in rats. Topical application of Calotropis gigantea latex extract ointment (10% w/w in petroleum gel) for 14 days significantly improved wound contraction when compared with control group of rats. The levels of hydroxyproline (collagen), hexosamine, uronic acid, DNA, RNA, and protein in the wound matrix revealed the pro-healing effects of Calotropis gigantea latex. The results obtained were comparable to those of nitrofurazone, a standard drug widely used for wound healing. The pro-wound-healing activity of the latex extract may be due to its high content of glycosides, flavonoids, phenolic compounds, and triterpenoids with antimicrobial and antioxidant properties. From the results obtained, it may be concluded that Calotropis gigantea latex has the potential to be developed into new therapeutic agent for wound healing.     

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 phytoconstituents from seed kernel of Entada pursaetha DC. and their molecular docking studies with glycogen synthase kinase 3-β

The present study was aimed at isolation of phytoconstituents from the seed kernel of Entada pursaetha DC. and screened for their wound healing activity by excision, incision, and dead space wound models on Swiss Albino Wistar rats. In correlation to in vitro wound healing activity, all phytoconstituents were subjected to molecular docking studies for the inhibition of glycogen synthase kinase 3-β (GSK3-β) protein, a main target for wound healing activity by Wnt signaling pathway. Among the phytoconstituents, entagenic acid showed good wound healing activity. In excision wound model, entagenic acid showed significant activity compared with other two phytoconstituents (Mean time of epithelialization in days is 18.08?±?0.01); in incision wound model, it showed tremendous activity with skin breaking strength of 655.67?±?4.14 than nitrofurazone (683.33?±?33.33) and also in dead space wound model entagenic acid showed very significant activity. Also in molecular docking studies, entagenic acid showed minimum binding (?8.79?kJ?mol^?1) and docking (?8.95?kJ?mol^?1) energy with good affinity toward active pocket, thus entagenic acid may be considered as good inhibitor of GSK3-β.     

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.     

Wound Healing Properties of Triterpenes from Buddleia scordioides in Diabetic Rats

Abstract

The pentacyclic triterpenes 3-O-α-l-rhamnopyranosyl-(1 → 4)-β -d-glucopyranosyl-(1 → 3)-[β -d-glucopyranosyl-(1 → 2)]-β -d- fucopyranosyl-23,28-dihydroxy-oleane-11, 13(18)-diene (1) and 3-O-α-l-rhamnopyranosyl-(1 → 4)-β -d-glucopyranosyl-(1 → 3)-[β -d-glucopyranosyl-(1 → 2)]-β -d-fucopyranosyl-16,23,28-trihydroxy-oleane-11,13(18)-diene (2) isolated from leaves of Buddleia scordioides Kunth (Loganiaceae) were studied for the effect on wound healing, using excision and incision wound modes. Significant increase in granulation tissue, tensile strength, hydroxyproline, total protein, and collagen contents was observed. There was significant reduction in the wound area measurement of the test group compared with that of controls. The efficacious prohealing effect may be due to increased collagen deposition as well as to better alignment and maturation.     

In diabetic foot infections antibiotics are to treat infection,not to heal wounds

Introduction: Diabetic foot ulcers, especially when they become infected, are a leading cause of morbidity and may lead to severe consequences, such as amputation. Optimal treatment of these diabetic foot problems usually requires a multidisciplinary approach, typically including wound debridement, pressure off-loading, glycemic control, surgical interventions and occasionally other adjunctive measures.

Areas covered: Antibiotic therapy is required for most clinically infected wounds, but not for uninfected ulcers. Unfortunately, clinicians often prescribe antibiotics when they are not indicated, and even when indicated the regimen is frequently broader spectrum than needed and given for longer than necessary. Many agents are available for intravenous, oral or topical therapy, but no single antibiotic or combination is optimal. Overuse of antibiotics has negative effects for the patient, the health care system and society. Unnecessary antibiotic therapy further promotes the problem of antibiotic resistance.

Expert opinion: The rationale for prescribing topical, oral or parenteral antibiotics for patients with a diabetic foot wound is to treat clinically evident infection. Available published evidence suggests that there is no reason to prescribe antibiotic therapy for an uninfected foot wound as either prophylaxis against infection or in the hope that it will hasten healing of the wound.     

苯妥英钠对大鼠伤口巨噬细胞的影响

本实验旨在研究苯妥英钠(PS)对伤口巨噬细胞(M_ф)的影响. 从置入大鼠背部伤口的聚乙烯醇海绵中收集巨噬细胞, 分别测定其吞噬功能, 肿瘤坏死因子α(TNF_α)和白介素1(IL-1)的释放以及对成纤维细胞增殖调节作用, 通过牵拉伤口组织致其断裂时溢出的水的重量而测定伤口牵张强度. 结果表明, 伤口M_ф的功能在伤后d 5达到高峰, PS 1,10,50 g·L^-1浓度依赖性地增加伤后d 5的伤口M_ф的数量, 吞噬功能, TNF_α和IL-1的释放, 增强M_ф对成纤维细胞增殖的刺激作用, 增强伤口牵张强度. 结果说明PS加速伤口愈合, 与其增强M_ф的功能有关.