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.     

Ethanol extract of Cotinus coggygria leaves accelerates wound healing process in diabetic rats

Context: Cotinus coggygria Scop. (Anacardiaceae) leaves that were used as wound healing in traditional Balkan and Anatolian folk medicine, could be potentially effective in treating diabetic wounds.

Objective: This study investigates biochemical and histological effects of ethanol extract of C. coggygria (CCE) on excision wound model in diabetic rats.

Materials and methods: This study was conducted on diabetic Wistar albino rats, which were injected by a single dose (50?mg/kg i.p.) streptozotocin. Afterward an excision wound model was created in all animals; diabetic control rats were applied topically simple ointment and diabetic treatment rats were applied topically 5% (w/w) ointment with CC, once a day during the experimental period. Malondialdehyde, glutathione and hydroxyproline levels in wound tissues were investigated at the end of 3rd, 7th, and 14th days. Histopathological examination was also performed.

Results: Hydroxyproline content was significantly increased in the CCE treated group versus control after the 3rd and 7th days (15.33 versus 11.83; 19.67 versus 15.67?mg/g, p?<?0.05; respectively). A statistically significant elevation in glutathione at the end of 3rd, 7th, and 14th days (5.13 versus 1.58, p?<?0.05; 4.72 versus 1.88, p?<?0.05; 3.83 versus 1.88?μmol/g, p?<?0.05, respectively) and a statistically significant decrease in malondialdehyde level at the end of 7th day (4.49 versus 1.48?nmol/g, p?<?0.05) were determined in the treated group versus control group. These results were also supported by histological analyses.

Discussion and conclusion: These findings indicate that CCE accelerated the cutaneous wound healing process in diabetic wounds, in confirmation of its traditional use.     

Novel microstructured sildenafil dosage forms as wound healing promoters

Purpose: Study the possible benefit of combining biodegradable polymers with sildenafil citrate (SC) in wound healing.

Method: Biodegradable micronized powdered formulations of SC were prepared by spray drying using chitosan (P₁) or chitosan/gum Arabic (P₂). Powders were characterized by differential scanning calorimetry, Scanning electron microscope, particle size analysis, flow and swelling behavior. The powders were also incorporated into microstructured gels and in vitro SC release from powders and gels was tested. In vivo wound healing acceleration was tested by measuring area contraction of excision wounds and histologically. Post-healing tensile strength (TS) for incision wounds in rats receiving powder formulations was tested.

Results: The powders were in the micron-size range showing no SC–polymers interaction. Powders had poor flow with angle of repose (θ) of 41 – 48°, and high moisture uptake reaching 107% for placebo powder P_o1. Good excision wound healing was seen with P₁ and G₁ formulations showing 98.4 and 98.5% reduction in wound area, respectively, compared with 83% for the control. Incision wounds were improved with P₁ showing TS value of 6.9 compared with 3.7 kg/cm² for control. Histological examinations supported.

Conclusion: Spray-dried chitosan/SC powder (P₁) and its gel form (G₁) could be promising wound healing promoters as supported by the histological examinations.     

Embelin accelerates cutaneous wound healing in diabetic rats

This study reports the effect of embelin (1) on cutaneous wound in streptozotocin (STZ)-induced diabetic rats. The effect was studied using excision, incision, and dead space models. In diabetic rats, topical application of embelin 5% (w/w) ointment showed a significant increase in wound contraction and better epithelialization, thereby facilitating the healing. Embelin was also active by the oral route (25 and 50 mg/kg) in the incision and dead space wound models. In incision wound model, wound granulation tissues were removed on 8th post-wounding day, and the hydroxyproline, hexosamine, total protein, and DNA contents were determined. In STZ diabetic rats, topical and oral applications of embelin showed an increase in hydroxyproline, hexosamine, total protein, and DNA contents. It also showed a significant increase in wound breaking strength. Embelin significantly increased granuloma tissue weight and breaking strength in dead space model. These results indicated that embelin accelerated wound healing in diabetic rat.     

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.     

Dermal wound healing potency of single alkaloid (betaine) versus standardized crude alkaloid enriched-ointment of Evolvulus alsinoides

Context: Evolvulus alsinoides Linn. (Convolvulaceae), well known as shankhpushpi in Ayurvedic text, is traditionally used for several healing purposes.

Objective: A comparative evaluation of dermal wound healing potential of acidic and basic alkaloid enriched-ointment (AAO and BAO) of aerial parts of E. alsinoides versus pure alkaloid, betaine (BEO), was undertaken.

Material and methods: The effect of topical application (50?mg/animal/day) of AAO-1%, AAO-2%, BAO-1%, BAO-2%, BEO-0.5% and BEO-1% was assessed through excision (14 days) and incision (10 days) models on rats. The percentage wound contraction, total protein content, and breaking strengths were determined followed by histopathological studies.

Results and discussion: The total alkaloid in acidic and basic alkaloid enriched fractions was found to be 0.1114 and 0.1134?μg/mL, respectively. Thus, 0.1528, 0.3056, 0.1380 and 0.2459?μg of total alkaloid were estimated to be present in AAO-1%, AAO-2%, BAO-1% and BAO-2%, respectively. AAO and BAO promoted wound healing activity significantly in both the models. Higher rate of wound contraction (p?<?0.001) with significant increase in protein content in the treatment groups (from 2.32 to 2.55) demonstrated stimulation of cellular proliferation and epithelization, which was further supported by histopathological reports. High skin breaking strength (mean value 393 in control was increased to the range of 535–572 in treated groups) proved a significant (p?<?0.001) wound healing potential of E. alsinoides. Early dermal and epidermal regeneration in drug-treated groups also confirmed the positive effect.

Conclusion: Observation of higher healing power of alkaloid enriched-ointment compared with single alkaloid ointment corroborated the synergy mechanism.     

Antiviral medications and corneal wound healing

Masked controlled rabbit studies were done to determine the toxic effects on corneal wound healing of the antiviral ointments 0.5% idoxuridine, 3% Ara A, and 3% acyclovir, and the antiviral drops 0.1% idoxuridine, 3% Ara AMP, and 1% trifluridine. Ara A, acyclovir, trifluridine and idoxuridine drops had no significant effects on the rate of closure of epithelial wounds. Idoxuridine ointment given 5 times a day significantly retarded the rate of epithelial wound closure, but not when given 4 times a day. Only Ara AMP caused a retardation of epithelial healing and an actual increase in the defect after 4 days of treatment. Histopathologically all drugs, except acyclovir, showed a toxic effect on the regenerating epithelium. All drugs, except acyclovir, showed retarded stromal wound healing with reduced bursting strength and collagen content. Ara AMP had increased bursting strength and collagen content possibly because of greater inflammation. Acyclovir, in comparison to all the other medications studied, appeared to have minimal to no toxic effects on experimental epithelial and stromal wound healing, and on this basis is the agent of choice for use in herpes simplex stromal keratitis with ulceration and as a prophylactic agent for long-term use after penetrating keratoplasty.     

Therapeutic potential of CDK5 inhibitors to promote corneal epithelial wound healing

Cyclin-dependent kinase 5 (CDK5) is generally considered to be a neuron-specific enzyme, and CDK5 inhibitors have most often been claimed for pharmacologic use in neurodegenerative diseases. However, recent findings indicate that CDK5 also has important functions in some non-neuronal cells, where it regulates such processes as differentiation, senescence, adhesion and migration. In particular, CDK5 activity has been shown to increase adhesion and decrease migration of corneal epithelial cells, both in vitro and in transgenic mouse models. Conversely, inhibition of CDK5 activity significantly enhances closure of corneal epithelial defects, suggesting a novel therapeutic use for CDK5 inhibitors. This review evaluates the therapeutic potential of currently available CDK5 inhibitors for this application and considers the types of corneal epithelial defects that may benefit from such treatment.     

吲哚青绿在白内障手术中前囊膜染色与切口愈合的临床观察

目的评价吲哚青绿晶状体前囊膜染色在连续环形撕囊中的有效性及其对术后角膜切口愈合的安全性。方法125例（125只眼）白内障患者随机分为2组观察组（吲哚青绿染色组）61只眼,对照组（空白组）64只眼。观察组采用吲哚青绿溶液前囊膜染色,对照组采用平衡盐灌注液作对比。结果观察组连续环形撕囊成功率96.72%,对照组连续环形撕囊成功率68.75%,2组差异有统计学意义（P〈0.05）;术后1d,3d,7d,1月,3月2组患者中连续环形撕囊成功者切口的透明角膜隧道的混浊程度：2组差异无统计学意义（P〉0.05）。结论吲哚青绿晶状体前囊膜染色能提高连续环形撕囊成功率,也不影响角膜切口的初期愈合过程。     

基于数据挖掘的中医药促进创面修复用药规律的研究

目的 通过整理、挖掘古代典籍和现代文献中促进创面修复的用药规律,为促进修复的临床用药提供新思路。方法 收集文献中记载的促进创面修复方剂,建立数据库,采用数据挖掘技术进行分析。结果 在关于中医药促进创面修复的古籍文献中,纳入75首方剂和203味中药,促进创面修复的核心药物有乳香、甘草、当归、白芷、黄柏、没药等,用药种类以清热药、活血化瘀药、补虚药、解表药、拔毒化腐生肌药为主。对16味核心药物进行聚类分析和关联规则分析,得出4个聚类组合和15组药对及药组关联规则。结论 创面修复方剂的用药规律以清热、活血化瘀、补虚、解表、拔毒化腐生肌为主,中医治疗创面应针对热病、血瘀、虚证、腐烂溃破、表证、中毒等因素进行辨证论治。     

The reduction in inflammation and impairment in wound healing by using strontium chloride hexahydrate

Background: Numerous growth factors, cytokine, mitogen and chemotactic factors are involved in wound healing. Even though inflammation is important for the stimulation of proliferative phase, excessive inflammation also causes impairment in wound healing. Strontium salts suppress keratinocyte-induced TNF-alpha and interleukin-1 and interleukin-6 in in vitro cultures. This study was conducted to determine the effects of administration of topical strontium chloride hexahydrate on wound healing through TNF-alpha and TGF-beta in surgical wound healing model of in-vivo rat skin.

Material and methods: Twenty-four rats were used in the study. After approximately 2?cm cutaneous–subcutaneous incision was horizontally carried out on the mid-neckline of the rats, the incision was again closed using 2.0 vicryl. The rats were assigned into three groups including eight rats in each group. Placebo emollient ointment and also the ointments, which were containing 5% and 10% strontium chloride hexahydrate and were prepared at the same base with placebo ointment, were administered to the groups by a blind executor twice a day for a week. At the end of seventh day, the rats were sacrificed and cutaneous and subcutaneous tissue of their wound site was resected for histopathological examination. Scoring of histopathological wound healing and scoring of tissue TNF-alpha and TGF-beta level with immunohistochemical staining were performed.

Results: The groups, to which both 5% and 10% strontium chloride hexahydrate was administered, had lower immunohistochemical TNF-alpha levels and histopathological wound scores compared to controls, which was statistically significant (p?Conclusion: Strontium chloride hexahydrate can lead to impairment in wound healing by suppressing inflammation through TNF-alpha.     

重组细胞珠蛋白抗衰老与创伤愈合的初步研究

本研究利用实验室纯化得到的重组细胞珠蛋白 (rCygb), 通过人永生化角质形成细胞 (HaCAT) H₂O₂氧化应激模型、小鼠皮下连续注射D-gal导致的皮肤衰老模型、CCl₄引起的大鼠急性肝损伤模型和大鼠皮肤创伤愈合模型, 对rCygb抗氧化、增强机体抗氧化酶活性、降低氧自由基含量、延缓皮肤衰老以及创伤愈合作初步研究。结果表明: rCygb可以提高总超氧化物歧化酶 (T-SOD)、谷胱甘肽过氧化物酶 (GSH-Px) 和过氧化氢酶 (CAT) 活性; 降低乳酸脱氢酶 (LDH) 和丙氨酸氨基转移酶 (ALT) 活性; 减少丙二醛 (MDA) 含量。皮肤切片展示rCygb可以促进新生血管生成、增加胶原表达和提高抗炎能力。研究结果显示: rCygb可通过改善机体清除氧自由基的能力, 延缓皮肤衰老和促进创伤愈合。     

Formulation and evaluation of Ocimum basilicum-based emulgel for wound healing using animal model

The main aim of the topically applied drugs is to provide local drug contact to the skin and minimize general absorption of drugs. Ocimum basilicum (OB) is popular for folk medicines, having official acceptance in many countries. The aim of this study was to formulate and evaluate the efficacy of topical application of OB-based emulgel on wound healing in animal model. The prepared formulations (OB emulgel) were assessed for FTIR analysis, stability studies, physical appearance, rheological behavior, spreadability, patch/sensitivity test and in vitro drug release. The in vivo wound healing effect was evaluated and compared with commercially available Silver Sulfadiazine cream Quench® in wound-induced rabbits by macroscopic and histopathological evidence. The OB extract/drug was compatible with the selected polymer and other excipients and indicated the suitability of the polymers/excipients for preparation of topical emulgel. The formulated OB emulgel exhibited good physical properties. The release profile of emulgel was satisfactory and released 81.71 ± 1.7% of the drug in 250 min. In vivo wound healing studies showed that OB emulgel exhibited the highest percent wound contraction similar to the commercial product (p > 0.05). This activity was statistically significant (p < 0.05) in comparison to control. Histopathological assessment showed marked improvement in the skin histological architecture after 16 days of OB emulgel treatment. In conclusion, the data demonstrated here signify the prospective of 5% OB emulgel as an innovative therapeutic approach in wound healing.     

N-containing compounds from Periplaneta americana and their activities against wound healing

Three new compounds, periplanamides A (1) and B (2), periplanpyrazine A (3), a new naturally occurring compound salicyluric acid methyl ester (6), and seventeen known compounds were isolated from the medicinal insect Periplaneta americana. The structures of the new compounds were elucidated on the basis of spectroscopic methods. The absolute configurations of 2 were assigned by computational methods. Biological activities of these isolates except 1, 9, 11, and 13 toward nitric oxide (NO) production, cell proliferation in HDFs, cell migration and angiogenesis in HUVECs were evaluated.     

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.     

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.     

The discovery and development of topical medicines for wound healing

Introduction: Chronic, nonhealing skin wounds claim >3% of the health-care budget in industrialized countries, and the incidence is rising. Currently, two parallel trends influence innovations within the field of wound healing: the need to reduce spread of antibiotic resistance and the emerging use of health economy and value-based models.

Areas covered: This review focuses on the discovery of drug candidates and development of treatments aiming to enhance wound healing in the heterogeneous group of patients with nonhealing wounds.

Expert opinion: Nonhealing wounds are multifaceted and recognized as difficult indications. The majority of products currently in use are medical device dressings, or concepts of negative pressure or hyperbaric oxygen treatment. Global best practice guidelines for the treatment of diabetic foot ulcers recommend debridement, redressing, as well as infection control, and are critical to the lack of coherent clinical evidence for many approved products in active wound care. To accelerate wound healing, there is an emerging trend toward biologics, gene therapy, and novel concepts for drug delivery in research and in the pipeline for clinical trials. Scientific delineation of the therapeutic mechanism of action is, in our opinion, vital for clinical trial success and for an increased fraction of medical products in the pharmaceutical pipeline.     

大黄素对家兔实验性皮肤创伤的促愈合作用及其机制

目的探讨大黄素治疗皮肤创伤的可能性及其作用机制。方法采用家兔皮肤切除伤创伤模型,同时滴加绿脓杆菌或金黄色葡萄球菌。大黄素(100~200μg·g-1)敷于创面,每天1次,连续7d或14d。观察创面面积、创面细菌数量和病理组织学改变。生化测定创面组织蛋白和羟脯氨酸(OHP)含量;免疫组化S-P法检测转化生长因子(TGF-β1)含量;逆转录聚合酶链反应测定TGF-β1mRNA表达;Western印迹分析Smad2,3,4和7表达。结果大黄素(100~200μg·g-1)随药物剂量和时间的增加而提高创面愈合百分率和降低感染创面表面细菌数;创面组织蛋白和羟脯氨酸的含量也随着剂量的增加而增加。病理结果显示,大黄素200μg·g-1明显促进创面炎性渗出物吸收、肉芽组织形成和表皮增生。随大黄素浓度的增加,与基质对照组相比,TGF-β1基因和蛋白的表达逐渐增高,均有显著差异;对Smad4蛋白表达无影响,大黄素150和200μg·g-1使Smad7蛋白表达降低;大黄素200μg·g-1使Smad3和Smad2表达增加,其他剂量则无影响。与rhEGF组相比,大黄素100和(或)150μg·g-1组使Smad2和Smad3表达明显下降。结论大黄素促进实验性皮肤创面的修复,其机制可能与TGF-β1和Smads信号转导通路有关。     

Novel preparation of transdermal drug-delivery patches and functional wound healing materials

The application of an electric field to a flowing medium can result in the formation of microscale and nanoscale structures suitable for drug delivery applications. We show that the design of the drug carrier can be varied and the release mechanism can be controlled by changing the physical state of the component containing the active agent. The structures formed include loaded micrometer-scale tubes and microcapsules and nanocapsules, which can also be utilized together to fabricate patches and wound healing materials. The aim of this study was to demonstrate novel processing of such patches and wound dressings. The processing used to generate these structures is carried out at the ambient temperature and is a versatile one-step operation suitable for a range of materials with low running costs and set-up costs without the degradation of the active drug component. The process can be multiplexed and requires no solvent extraction. It also offers pharmaceutical applications outside the remit of the potential uses presented.