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1.
Biomed Res Int ; 2024: 6758817, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38899039

RESUMO

Materials and Methods: In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with MRSA. Various treatments were applied to the burn wounds daily, including Myrtus ointment, silver nanoparticles, silver nanoparticles-Myrtus ointment, silver sulfadiazine-Myrtus ointment, silver sulfadiazine 1%, mupirocin ointment, and a positive control. The study measured the antimicrobial effects, wound area, percentage of wound healing, antioxidant capacities, malondialdehyde, and nitric oxide concentrations in the serum of the rats. Data analysis was performed using GraphPad software, with one-way ANOVA and Tukey's tests used to determine the statistical significance of the results. Results: Rats treated with Myrtus ointment, silver nanoparticles-Myrtus ointment, and mupirocin had reduced bacterial growth compared to the positive control group, nanoparticle ointment, and silver sulfadiazine (P < 0.05). The wound area of the Myrtus ointment group decreased significantly on the seventh and fourteenth days, as well as the level of MDA and nitric oxide, compared to the other groups. In Myrtus and silver sulfadiazine-Myrtus ointment increased the thickness of the epidermis and dermis compared to the other groups. Conclusion: Based on the anti-inflammatory, antimicrobial, and wound healing properties of Myrtus, with further studies, an ointment of this plant may be used as a main or complementary treatment for burn wound infections caused by MRSA.


Assuntos
Anti-Inflamatórios , Queimaduras , Staphylococcus aureus Resistente à Meticilina , Myrtus , Pomadas , Extratos Vegetais , Folhas de Planta , Ratos Wistar , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Queimaduras/tratamento farmacológico , Queimaduras/microbiologia , Extratos Vegetais/farmacologia , Masculino , Pomadas/farmacologia , Ratos , Anti-Inflamatórios/farmacologia , Folhas de Planta/química , Myrtus/química , Anti-Infecciosos/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Nanopartículas Metálicas/química , Sulfadiazina de Prata/farmacologia
2.
J Cosmet Dermatol ; 23(4): 1233-1242, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38174442

RESUMO

BACKGROUND: With the increasing age of the westernized population, there is also increasing economic and aesthetic interest in reducing the signs of skin aging. Additionally, the physical aspect of aging can be displeasing and have detrimental effects psychologically in individuals. Probiotics have shown potential as anti-aging agents, albeit proper studies are needed to confirm their potential. AIMS: Proving that Lactiplantibacillus plantarum LB244R® could alleviate aging signs relative to its placebo vehicle. PATIENTS/METHODS: In total, 46 subjects were randomly assigned either the ointment with live bacteria, L. plantarum LB244R® or its vehicle ointment, and had to use the assigned ointment twice daily for 56 days. On Day 0, Day 28, and Day 56 subepidermal low echogenic band (SLEB) thickness, dermal density, skin firmness and elasticity, skin hydration, transepidermal water loss (TEWL), skin pH, collagen fiber visualization using confocal microscopy, Crow's feet, spot score, skin smoothness, and complexion radiance were assessed by dermatologists. RESULTS: All parameters except TEWL improved relative to their baseline (D0) for the active group. L. plantarum LB244R® improved SLEB thickness, dermal density, skin elasticity, skin hydration, and Crow's feet wrinkle score relative to the placebo vehicle ointment. CONCLUSION: The study demonstrates an anti-aging effect of L. plantarum LB244R® for topical skin use in the first double-blinded, vehicle-ointment placebo-controlled clinical study.


Assuntos
Envelhecimento da Pele , Pele , Humanos , Pomadas/farmacologia , Método Duplo-Cego , Envelhecimento
3.
J Tissue Viability ; 33(1): 135-143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38290935

RESUMO

BACKGROUND: Wound healing poses a challenging therapeutic scenario, requiring diverse clinical approaches. OBJECTIVES: This study aims to assess the wound-healing potential of Salix aegyptiaca's flower ointment compared to phenytoin, considering the active constituents of S. aegyptiaca and its traditional usage. METHODS: Initially, the active components of S. aegyptiaca were isolated and identified through the GC-MS technique. Subsequently, for the experimental intervention, thirty-five rats were divided into five distinct groups: control (C), phenytoin (F), and three S. aegyptiaca ointment groups at different concentrations (5 % - S5, 25 % - S25, and 50 % - S50). Anesthesia was administered, and wounds were induced on the animals' necks following a standard procedure. These wounds were then treated for a duration of 21 days. Wound healing progress was quantified, and histopathological assessments were conducted using hematoxylin and eosin staining and Mason's trichrome staining. RESULTS: The main active compounds of S. aegyptiaca, namely n-hexadecanoic acid and oleic acid, were identified via GC-MS analysis. Although the initial group weights did not show a significant difference (P = 0.271), a significant variation was observed in the final weights (P = 0.003). The S50 group exhibited a lower wound healing rate than the S25 group on the 7th and 14th days but surpassed it on the 21st day (C < F < S5≈S25

Assuntos
Salix , Lesões dos Tecidos Moles , Ratos , Animais , Fenitoína/farmacologia , Fenitoína/uso terapêutico , Pomadas/farmacologia , Pomadas/uso terapêutico , Pele/lesões , Cicatrização , Modelos Animais
4.
Int J Mol Sci ; 24(20)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37894801

RESUMO

The administration of therapeutic drugs through dermal routes, such as creams and ointments, has emerged as an increasingly popular alternative to traditional delivery methods, such as tablets and injections. In the context of drug development, it is crucial to identify the optimal doses and delivery routes that ensure successful outcomes. Physiologically based pharmacokinetic (PBPK) models have been proposed to simulate drug delivery and optimize drug formulations, but the calibration of these models is challenging due to the multitude of variables involved and limited experimental data. One significant research gap that this article addresses is the need for more efficient and accurate methods for calibrating PBPK models for dermal drug delivery. This manuscript presents a novel approach and an integrated dermal drug delivery model to address this gap that leverages virtual in vitro release (IVRT) and permeation (IVPT) testing data to optimize mechanistic models. The proposed approach was demonstrated through a study involving Desoximetasone cream and ointment formulations, where the release kinetics and permeation profiles of Desoximetasone were determined experimentally, and a computational model was created to simulate the results. The experimental studies showed that, even though the cumulative permeation of Desoximetasone at the end of the permeation study was comparable, there was a significant difference seen in the lag time in the permeation of Desoximetasone between the cream and ointment. Additionally, there was a significant difference seen in the amount of Desoximetasone permeated through human cadaver skin at early time points when the cream and ointment were compared. The computational model was optimized and validated, suggesting that this approach has the potential to bridge the existing research gap by improving the accuracy and efficiency of drug development processes. The model results show a good fit between the experimental data and model predictions. During the model optimization process, it became evident that there was variability in both the permeability and the partition coefficient within the stratum corneum. This variability had a significant and noteworthy influence on the overall performance of the model, especially when it came to its capacity to differentiate between cream and ointment formulations. Leveraging virtual models significantly aids the comprehension of drug release and permeation, mitigating the demanding data requirements. The use of virtual IVRT and IVPT data can accelerate the calibration of PBPK models, streamline the selection of the appropriate doses, and optimize drug delivery. Moreover, this novel approach could potentially reduce the time and resources involved in drug development, thus making it more cost-effective and efficient.


Assuntos
Desoximetasona , Pele , Humanos , Pomadas/farmacologia , Pele/metabolismo , Absorção Cutânea , Simulação por Computador , Administração Cutânea
5.
Phytomedicine ; 119: 155000, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37541071

RESUMO

BACKGROUND: Lychnophora ericoides Mart, also known as the Brazilian arnica or fake arnica, belongs to the Asteraceae family. Leaves and roots are used in alcoholic and hydroalcoholic preparations for the treatment of wounds, inflammation, and pain. PURPOSE: The present study aimed to investigate the effects of L. ericoides ethanolic extract (EELE) on cutaneous wound healing and the mechanisms of action involved. METHODS: A total of 72 C57BL/6 mice were randomly divided into four groups of six animals each. An excisional wound was made in the dorsal region of each mouse. The test groups were topically treated with the vehicle, a positive control commercial reference drug, EELE ointment (5%), and EELE ointment (10%). The treatments were applied over 14 days. The wound area was measured every two days to verify the wound closure kinetics. On days 3, 7, and 14 the wound tissue samples were processed for Hematoxylin and Eosin, Masson-Trichrome, and Toluidine blue staining. The expression of renin-angiotensin system (RAS) components, the vascular growth factor-A (VEGF-A), the basic fibroblast growth factor (FGF-2), and type I collagen genes were evaluated. Phytochemical analyses were performed using HPLC-DAD and HPLC-MS/MS. RESULTS: The EELE (10%) significantly reduced the wound area compared to the treatments used for the other groups. Histological analysis demonstrated that wounds treated with L. ericoides for 14 days developed improved anatomical skin features, healed with hair follicles and sebaceous glands, increased collagen production and angiogenesis, and decreased the number of mast cells at the injury site. Real-time PCR data demonstrated that groups treated with EELE (10%) showed increased Type I collagen, VEGF-A, FGF-2, and AT1R and decreased ACE II and receptor MAS. The healing action of L. ericoides may be related to the presence of phenolic compounds, such as phenolic acids, chlorogenic acid derivatives, and C-glycoside flavonoids. CONCLUSION: Topical treatment with EELE increases important factors for wound healing: FGF, VEGF, collagen formation, and the expression of the proliferative axis of the renin-angiotensin system. For the first time, the present study shows the healing action of L. ericoides at the molecular level in an animal model. This process can be used as an alternative therapy for wound healing and the development of herbal therapy.


Assuntos
Arnica , Asteraceae , Camundongos , Animais , Arnica/metabolismo , Etanol/química , Colágeno Tipo I/metabolismo , Brasil , Espectrometria de Massas em Tandem , Pomadas/metabolismo , Pomadas/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator 2 de Crescimento de Fibroblastos/farmacologia , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Asteraceae/química , Cicatrização , Pele , Colágeno/metabolismo
6.
BMC Cancer ; 23(1): 401, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142953

RESUMO

BACKGROUND: Regorafenib, a multikinase inhibitor, causes a high frequency of hand-foot skin reactions (HFSRs). The present study evaluated the efficacy of topical aluminum chloride, a perspiration suppressant, in reducing the severity of hand-foot skin reactions (HFSRs) caused by regorafenib. METHODS: The present single-arm study included patients with metastatic colorectal cancer receiving regorafenib. Aluminum chloride ointment was applied topically one week prior to the start of regorafenib treatment, and the observation period was 12 weeks. The primary endpoint was the incidence of regorafenib-related grade 3 HFSR. Secondary endpoints were the incidence of all grades of HFSR, time to any grade of HFSR, time to improvement from grade 2 or higher to grade 1 or lower, treatment discontinuation rate, treatment interruption rate or dosage reduction due to HFSR, and incidence of adverse effects of aluminum chloride. RESULTS: In total 28 patients were enrolled, and 27 patients were analyzed. The incidence of grade 3 HFSR was 7.4%, meeting the primary endpoint. The incidence of all grades of HFSR was 66.7%, and the median time to the occurrence of any grade of HFSR was 15 days. No patients discontinued or reduced the regorafenib dosage because of HFSR. The most common reason for the interruption of regorafenib therapy was liver dysfunction in nine patients (33%) and HFSR in three patients (11%). No serious adverse events related to aluminum chloride were observed. CONCLUSIONS: Aluminum chloride ointment, a drug commonly used in routine practice to treat hyperhidrosis, is safe to use, has no serious side effects, and may be effective in reducing the occurrence of severe, regorafenib-related HFSR. TRAIL REGISTRATION: ClinicalTrials.gov. identifier: jRCTs031180096, Registered on 25/01/2019.


Assuntos
Compostos de Fenilureia , Pele , Humanos , Cloreto de Alumínio/farmacologia , Pomadas/farmacologia , Compostos de Fenilureia/efeitos adversos , Pele/patologia
7.
Biol Pharm Bull ; 46(5): 707-712, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37121696

RESUMO

Wound-healing deficits of the skin, one of the most common complications in patients with diabetes, delay wound healing, significantly reducing the patient's QOL. Therefore, the topical treatment of wound areas with drug-containing ointments and dressings is important. In this study, we investigated the effect of various ointment bases on skin wound healing in normal and streptozotocin-induced diabetic rats (STZ rats). Three ointment bases were used: white ointment (oil-based), absorbent cream (emulsion-based, w/o), and macrogol ointment (water-based). Skin wound healing in STZ rats was delayed compared with that in normal rats. Each of the three ointment bases was applied to the skin wound area in normal rats, and there was no difference in the therapeutic effect. The therapeutic effect of both white ointment and absorbent cream was higher in the STZ rats group than that in the non-treated group, and delayed wound healing was observed in STZ rats treated with macrogol ointment. In conclusion, skin wound healing in STZ rats is affected by the properties of the ointment base, and it is important to use an ointment base that controls the drying of the wound area in STZ rats. These findings provide information for the selection of ointment bases useful for application to skin wounds in patients with diabetes.


Assuntos
Diabetes Mellitus Experimental , Bases para Pomadas , Ratos , Animais , Bases para Pomadas/uso terapêutico , Bases para Pomadas/farmacologia , Pomadas/farmacologia , Pomadas/uso terapêutico , Estreptozocina , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Qualidade de Vida , Pele , Polietilenoglicóis/farmacologia
8.
Appl Biochem Biotechnol ; 195(11): 6516-6536, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36870025

RESUMO

Wound care management aims at stimulating and improving healing process without scar formation. Although various plants have been reported to possess wound healing properties in tribal and folklore medicines, there is a lack of scientific data to validate the claim. In this aspect, it becomes inevitable to prove the efficacy of naturally derived products at pharmacological levels. Couroupita guianensis as a whole plant has been reported to exhibit wound healing activity. The leaves and fruit of this plant have been utilized in folkloric medicine to cure skin diseases and infections for many years. However, to the best of our knowledge, no scientific studies have been conducted to verify the wound healing properties of C. guianensis fruit pulp. Therefore, the present study seeks to investigate the wound healing potential of C. guianensis fruit pulp using an excision wound model in Wistar albino male rats. This study indicated that the ointment prepared from crude ethanolic extract of C. guianensis fruit pulp facilitated wound contraction that were evidenced by a greater reduction in the wound area and epithelialization period and increased hydroxyproline content. The experimental groups treated with low and mid dose of C. guianensis ethanol extract (CGEE) ointments had shown a wound closure of 80.27% and 89.11% respectively within 15 days, which is comparable to the standard betadine ointment which showed 91.44% healing in the treated groups. Further, the extract influenced the expression of genes VEGF and TGF-ß on post wounding days that clearly explained the strong correlation between these genes and wound healing in the experimental rats. The animals treated with 10% CGEE ointment showed a significant upregulation of both VEGF and TGF-ß as compared with other test and standard groups. These findings provide credence to the conventional application of this plant in the healing of wounds and other dermatological conditions, and may represent a therapeutic strategy for the treatment of wounds.


Assuntos
Frutas , Extratos Vegetais , Ratos , Animais , Ratos Wistar , Extratos Vegetais/farmacologia , Pomadas/farmacologia , Fator A de Crescimento do Endotélio Vascular , Cicatrização , Fator de Crescimento Transformador beta
9.
Parasitol Int ; 93: 102720, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36516945

RESUMO

The discovery of new effective and safe antimalarial drugs is mandatory. In this report, we formulate and evaluate transdermal (td) 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the Plasmodium berghei rodent malaria parasite in vivo model. The selected solvent for the ointment type of td N-89 was polyethylene glycol (PEG) [PEG400:PEG 4000 = 8:1 (v/w)]. We tested different application areas of 4, 6, and 8 cm2 on the shaved backs of mice. Pharmacokinetic (PK) analysis of N-89 parameters after a single 4 cm2 transdermal application revealed that the Tmax was 2 h, the T1/2 was 1.9 h, and the AUC was 1951.1 ng.h/mL. More than 10 ng/mL of plasma concentration was maintained for 12 h. The ED50 values for the 4, 6, and 8 cm2 application areas in a 4-day suppressive test were 18.9, 25.1, and 26.8 mg/kg, respectively. We additionally tested the cure effect of td N-89 in mice at a dose of 60 mg/kg, twice daily for 4 days at 0.2% parasitemia. Parasites disappeared following day 7 post-treatment in all td N-89 treated groups. Mice were cured without any parasite recurrence or dermal irritation. In conclusion, this study determined for the first time the PK parameters and effect of a new ointment type of td N-89. This suggests that transdermal treatment with N-89 is an effective and safe alternative route for the treatment of malaria, especially in children.


Assuntos
Antimaláricos , Malária , Camundongos , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Pomadas/farmacologia , Pomadas/uso terapêutico , Malária/tratamento farmacológico , Malária/parasitologia , Plasmodium berghei , Parasitemia/tratamento farmacológico
10.
Biotech Histochem ; 98(2): 94-111, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36040350

RESUMO

Impaired diabetic wound healing causes foot ulcers. We investigated egg yolk oil for skin wound healing in streptozotocin (STZ) induced diabetic rats. Rats were allocated into three groups of six. Group 1, nondiabetic control group, was treated topically with 2% fusidic acid ointment. Group 2, STZ diabetic control, was treated topically with 2% fusidic acid ointment. Group 3, STZ diabetic group, was treated topically with egg yolk oil. Three days after STZ injection, two full thickness excisional skin wounds were created on the back of each animal. Wound diameter was measured for 14 days and wound contraction was calculated. Re-epithelization time also was determined. Three rats from each group were sacrificed on experimental day 7 and the remaining rats on day 14. Wound samples were examined using hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, Taenzer-Unna orcein and toluidine blue staining. Expression of endoglin (CD105), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) were investigated using immunohistochemistry. Egg yolk oil increased the proliferation of epithelial cells and angiogenesis, and stimulated collagen deposition in the lesion area. Egg yolk oil increased CD105, EGF and VEGF expression in blood vessels, and EGF and VEGF expression in epidermis of the lesions. The predominant fatty acids in egg yolk oil are oleic, palmitic and linoleic, which likely were responsible for the beneficial effects of egg yolk oil on diabetic wound healing. Egg yolk oil appears to be a promising therapeutic agent for healing of diabetic wounds.


Assuntos
Diabetes Mellitus Experimental , Fator A de Crescimento do Endotélio Vascular , Ratos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Estreptozocina/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Fator de Crescimento Epidérmico , Pomadas/farmacologia , Gema de Ovo/metabolismo , Ácido Fusídico/farmacologia , Cicatrização , Pele/patologia
11.
Arch Razi Inst ; 78(5): 1472-1482, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38590675

RESUMO

Scabies is considered an external parasite notorious for its high prevalence causing severe and contagious skin lesions in humans and animals worldwide. This study has introduced a medicine to treat dogs infested with scabies (variants of Demodex, Sarcoptes, Psoroptes, Otodectes, etc.). The present study offers a no-side-effect herbal formulation to treat dogs infested with scabies. Unlike oral and injectable medicines, which take the form of an ointment and are topically applied on-site, this medicinal formulation can be easily used without concerns over its side effects or consumption dosages. This medicinal formulation requires no skin rinsing due to its herbal and high skin absorption properties, as recovery may take less than a month with a maximum of two times of application. To carry out the experiment, 25 sick dogs with various breeds and ages suspected of scabies were gathered. Following accurate morphological examinations of all the samples, a deep skin chip of the lesion site was provided, which was examined by a microscope. Then, 13 dogs (Mix, Terrier, Pug, Husky, Spitz) were infested with Demodex scabies and 12 dogs (Pittbull, Mix, Shih Tzu, Terrier, Boxer, Setter) with Sarcoptic scabies. The prepared product was topically administered at a constant 2% dosage to the bodies of all the samples. To prepare the ointment, 1 g of Borax (Na2B4O7·10H2O) was first dissolved in 35 g deionized water and heated to 70°C. Then, 45 g of liquid paraffin (CnH2n+2) was mixed with 1 g of Carvacrol (C10H14O) and 1 g of geranium (C10H18O) and stirred well to become a phase. Later, 17 g of the melted beeswax (C15H31COOC30H61) was added to the liquid paraffin compound. In the end, the aqueous phase was added to the oil phase, and the mixture process immediately began in one direction with a glass stirrer and continued until the product cooled down. Essential oils (EO) was obtained by steam distillation of fresh Thyme and Rose-Acented Geranium in a stainless steel distillation apparatus (alembic) for 3 h. The main components of the essential oils used in the formulation were performed using a Hewlett-Packard GC system interfaced with a mass spectrometer equipped with an HP5-MS capillary column (30 m, 0.32 mm, 0.25 µm film thicknesses). For GC-MS detection, electron ionization with ionization energy of 70 eV was used. To examine the presence of scabies, weekly skin sampling was performed, and the treatment continued until 30 days, when no skin chip of the scabies was noted. The findings revealed that the formulation developed no side effects and removed the daily use, as it could be administered once or twice a week. Also, complete recovery of scabies in all the breeds was found to be less than a month at most. This medicinal formulationcan be easily used without concerns over its side effects or consumption dosages. This study introduced a herbal formulation with effective herbal ingredients without any side effects to treat the sarcoptes and demodex parasites; unlike other chemical compounds, this medicinal formulation has no side effects, while some other formulations could develop side effects.


Assuntos
Óleos Voláteis , Parasitos , Escabiose , Humanos , Animais , Cães , Escabiose/tratamento farmacológico , Escabiose/veterinária , Escabiose/patologia , Óleo Mineral/farmacologia , Óleo Mineral/uso terapêutico , Pomadas/farmacologia , Pomadas/uso terapêutico , Sarcoptes scabiei , Melhoramento Vegetal , Extratos Vegetais/farmacologia , Óleos Voláteis/farmacologia
12.
J Oleo Sci ; 71(12): 1777-1788, 2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36336343

RESUMO

Eucalyptol is a major volatile constituent among well-known wound healing medicinal plants. The current study evaluated eucalyptol wound healing activity in the rat's third-degree skin-burn model. The parameters, i.e., skin-healing, oxidative/antioxidant markers, pro-/anti-inflammatory markers, were evaluated after 1- and 2-weeks of treatment regimens with 5% eucalyptol ointment. Eucalyptol-loaded ointment base of 5% w/w strength was formulated using fusion method and physically evaluated for consistency, stability, and homogeneity. A 25-rats were divided randomly into intact, negative control (untreated), silver sulfadiazine (SS, positive control), 1-week, and 2-weeks treated eucalyptol groups. Using an aluminum cylinder (120℃, 10 second duration), 3rd-degree skin burns were created on the rat's dorsum. Skin biopsies were collected at the end of the experiment for biochemical and histological investigations. Compared to the negative group; time-dependent wound size reduction and decreased edema were observed in eucalyptol-treated animals. Histopathological examinations demonstrated epidermis integrity, decreased neutrophil, and increased capillaries number in the 2-weeks and SS groups, compared to the negative and 1-week treated eucalyptol groups. Compared to the untreated animals, the 1- and 2-weeks eucalyptol treated groups' demonstrated significantly increased antioxidant superoxide dismutase (SOD, p=0.002 and p=0.003, respectively) and reduced lipid peroxide (LP, p=0.005 and p=0.0006, respectively). However, a significant increment of catalase (CAT, p=0.0009) was found only in the 2-weeks of eucalyptol group at a level of 2.42 ± 0.39 ng/g compared to 1.14 ± 0.04 ng/g in the untreated animals. Also, significant reductions in the cytokines, IL-1b, IL-6, and TNF-α (p < 0.05); and increase in the pro-angiogenic marker, IL-10, were detected in the 2-weeks (p=0.001) and SS (p=0.002) treated animals compared to the negative and 1-week eucalyptol treated groups. The study concluded that eucalyptol induced significant duration-based wound healing properties attributed to its antioxidant and anti-inflammatory effects.


Assuntos
Antioxidantes , Queimaduras , Ratos , Animais , Pomadas/farmacologia , Pomadas/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Eucaliptol/farmacologia , Eucaliptol/uso terapêutico , Cicatrização , Queimaduras/tratamento farmacológico , Queimaduras/patologia , Pele , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
13.
Cells ; 11(22)2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36429048

RESUMO

Bone defects and fractures heal slowly compared with injuries to other tissues, creating a heavy burden for patients, their families, and society. Alongside conventional treatment methods for fractures and bone defects, adjuvant therapies play an important but underappreciated role. In a previous study, we found that systemic administration of flufenamic acid promoted osteogenesis in vivo, but its side effects limited the application of our findings. In the present study, we assess the effects of external butyl flufenamate ointment on the healing of cranial defects in mice. We found that application of butyl flufenamate ointment on the surface of the skin accelerated the healing of cranial defects in mice by promoting BMP2 secretion from mouse-skin mesenchymal stem-cells. These findings indicate that butyl flufenamate ointment has potential therapeutic value for treating superficial fractures or bone defects while avoiding the toxicity and side effects of systemic medication, representing a safe and convenient adjuvant therapy to promote healing of superficial bone defects and fractures.


Assuntos
Fraturas Ósseas , Células-Tronco Mesenquimais , Camundongos , Animais , Ácido Flufenâmico/farmacologia , Pomadas/farmacologia , Regeneração Óssea , Fraturas Ósseas/tratamento farmacológico , Proteína Morfogenética Óssea 2/farmacologia
14.
Molecules ; 27(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36144568

RESUMO

Phytocosmetic is an important aspect of traditional medicine in several cultures. Researchers are now focusing to find new and effective ingredients of natural origin. Propolis is a natural beehive product extensively used in traditional medicine. We aimed in the present study to investigate the potential use of propolis as an aesthetic and phytotherapeutic constituent in phytocosmetics. Propolis was extracted using 80% ethanol. Total phenolic and flavonoid contents were determined calorimetrically. Free radical scavenging ability and reducing capacity were evaluated using four assays and expressed as IC50 values. Antibacterial activity was evaluated by the determination of minimum inhibitory concentration (MIC) on 11 Gram-positive and Gram-negative bacteria. The wound healing activity of 30% ethanolic extract and propolis ointment was studied using excision wounds in the anterio-dorsal side of the rats. The phenolic acid composition of the tested propolis was investigated using UFLC/MS-MS analysis. The tested propolis was rich in phenolic and flavonoid content and demonstrated an interesting antibacterial and antioxidant activity. Wounds treated with propolis appear to display a lesser degree of inflammation. Chemical analysis led to the identification of 11 phenolics. Among them, five are considered as main compounds: Chlorogenic acid (48.79 ± 5.01 ng/mL), Gallic acid (44.25 ± 6.40 ng/mL), Rutin (21.12 ± 3.57 ng/mL), Caffeic acid (28.19 ± 4.95 ng/mL), and trans-cinnamic acid (20.10 ± 6.51 ng/mL). Our results indicated that propolis can not only be used as a cosmetic ingredient but also be used as a preventative and curative constituent, which might be used as a barrier when applied externally on infected and non-infected skin.


Assuntos
Própole , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antioxidantes/química , Ácido Clorogênico/farmacologia , Etanol/farmacologia , Flavonoides/análise , Flavonoides/farmacologia , Radicais Livres/farmacologia , Ácido Gálico/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Pomadas/farmacologia , Fenóis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Própole/química , Ratos , Rutina/farmacologia
15.
Sci Rep ; 12(1): 14327, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35995975

RESUMO

The role of angiotensin receptor blocker in wound healing and cutaneous fibrosis has become a hotspot in recent years. We have developed a losartan cream that is comparable to triamcinolone ointment in inhibiting scarring. Considering the effects of chitosan and asiaticoside on wound healing and scarring, we added them to the losartan cream this time and improved the formula, expecting to get a better anti-scarring effect. The effects of creams were investigated on mouse scar model with triamcinolone ointment, onion extract gel, and commercial asiaticoside cream set as positive controls. A preliminary exploration of the mechanism involved in TGF-ß/Smad pathway was performed in vivo and in vitro. With all results of anti-scarring, the compound losartan cream (containing chitosan, asiaticoside, and losartan) shows the best effect, followed by the chitosan asiaticoside cream. The treatment of the compound losartan cream inhibited expression of TGF-ß1, collagen, and Smads, and decreased phosphorylation of Smad in vivo. These inhibitory effects were also confirmed in vitro. Our findings indicated that the compound losartan cream could inhibit scarring via TGF-ß/Smad pathway. This cream might be an effective option for scar treatment.


Assuntos
Cicatriz , Losartan , Animais , Quitosana/farmacologia , Cicatriz/tratamento farmacológico , Cicatriz/patologia , Losartan/farmacologia , Camundongos , Pomadas/farmacologia , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Triancinolona
16.
Cytokine ; 158: 156012, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36030705

RESUMO

Present study was conducted to undermine the wound healing potential of mangiferin vis a vis its molecular dynamics in immunocompromised excisional rat model. 120 rats were randomly and equally divided into five groups viz. group I (Healthy control), group II (Immunocompromised control), group III (Immunocompromised group treated with silver sulphadiazine), group IV (Immunocompromised group treated with 2.5 %Mangiferin) and group V (Immunocompromised group treated with 5 %Mangiferin). Immuno compromised state was achieved following intramuscular injection of Hydrocortisone @ 80 mg/kg body weight. Study was conducted for a period of 28 days. Six animals from each group were humanely sacrificed at weekly interval till day 28th of study. Planimetric analysis, biochemical studies viz. hydroxyproline assay, total protein and DNA content, antioxidative potential through LPO assay was done along with molecular studies involving expression profiling of IL1ß, TNFα and COX-2 and Immunohistochemistry of angiogenic marker i.e. VEGF was performed to undermine the pharmacodynamics of mangiferin. Histopathological studies including H&E and Masson's Trichome was also performed to study histoarchitectural changes in wound healing and reparative process following application of mangiferin ointment. Study revealed significant (P ≤ 0.05) reduction in wound area measurement and significant (P ≤ 0.05) increase in wound contraction (%) following mangiferin administration in immunocompromised rats. Hydroxyproline, DNA and total protein showed significant (P ≤ 0.05) increase in skin tissues of mangiferin treated immunocompromised rats. LPO assay revealed significant (P ≤ 0.05) reduction in mangiferin treated animals. Histopathological studies of skin tissues revealed complete restoration advocating grade III of healing in 2.5% mangiferin treated group. Higher expression and strong signal intensity of VEGF was noticed in 2.5% mangiferin treatment group along with significant (P ≤ 0.05) upregulation IL1ß and TNFα on day 7 in 2.5% mangiferin treatment group with significant (P ≤ 0.05) down regulation of COX-2 in mangiferin treatment group as compared to other groups i.e. group II and III. It is concluded from our study that mangiferin facilitates wound healing through improved wound closure, organized deposition of collagen deposition and granulation matrix formation.


Assuntos
Xantonas , Animais , Ciclo-Oxigenase 2/metabolismo , Glucosídeos/farmacologia , Hidroxiprolina/metabolismo , Hidroxiprolina/farmacologia , Interleucina-1beta/metabolismo , Pomadas/metabolismo , Pomadas/farmacologia , Ratos , Pele/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Xantonas/metabolismo , Xantonas/farmacologia
17.
J Ethnopharmacol ; 296: 115464, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35714880

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Remijia ferruginea DC. (Rubiaceae) (syn. Cinchona ferruginea A.St.-Hil.) is used in traditional medicine for the treatment of wounds, fever and malaria. AIM: This study investigated in vitro the proliferative and antioxidant effects of hydroalcoholic extract of leaves of R. ferruginea (HERF) and in vivo the healing effect of ointment based on HERF. MATERIALS AND METHODS: The plant extract was characterized by liquid chromatography/mass spectrometry. Cell proliferation assays and in vitro antioxidant activity were performed. In in vivo assays, wound contraction ax was evaluated, as well as histological analyzes such as cellularity, proportion of blood vessels and collagen type I and III index. In addition, analyzes of the antioxidant enzymes SOD, CAT and GST were performed. RESULTS: Our results showed in the chromatographic analysis that catechin, rutin and quercetin were the main phenolic compounds in the plant extract and may be responsible for the antioxidant and proliferative effects (p < 0.05). In addition, these compounds were found in higher concentration in leaves collected in spring. The ointment containing HERF was able to modulate tissue morphology, increasing cell proliferation, blood vessels, being able to stimulate the production of collagen fibers type I and III, (p < 0.05) contributing to scar tissue maturation and resistance. CONCLUSION: Our findings indicated that the three doses of HERF tested (1%, 3% and 5%) can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.


Assuntos
Antioxidantes , Rubiaceae , Animais , Antioxidantes/uso terapêutico , Pomadas/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Ratos , Ratos Wistar
18.
Clin Transl Med ; 12(5): e790, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35522900

RESUMO

BACKGROUND: In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed. METHODS AND FINDINGS: In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double-blind and placebo-controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild-to-severe AD (EudraCT:2016-003501-33). ATx201 has a narrow minimal inhibitory concentration distribution (.125-.5 µg/ml) consistent with its mode of action - targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin-resistant S. aureus. In a Phase 2 trial in patients with mild-to-severe AD (N = 36), twice-daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle. CONCLUSION: These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.


Assuntos
Dermatite Atópica , Staphylococcus aureus Resistente à Meticilina , Microbiota , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Humanos , Camundongos , Niclosamida/farmacologia , Pomadas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus
19.
Aesthetic Plast Surg ; 46(5): 2580-2587, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35614156

RESUMO

BACKGROUND: Annually, millions of people suffer from skin scars' psychological and physical disadvantages. Pathologic scars prevention is challenging and requires developing feasible and effective therapeutic strategies. Regarding promising results of losartan (an angiotensin 1 receptor inhibitor) on skin scar in preclinical studies, we aimed to assess the losartan ointment's impact on surgical scars in a clinical setting. MATERIAL AND METHOD: Twenty-four patients with surgical wounds were enrolled from Razi hospital's plastic and reconstructive surgery department. The patients were trained to apply ointments 14-18 days post-surgery on the determined scar side, twice a day for 6 months. Two dermatologists independently evaluated scar formation at 3 and 6-month follow-ups using the Vancouver Scar Scale (VSS) score. RESULT: Twenty-four female patients with cosmetic surgeries were included. The mean VSS score of losartan-treated sides was 7.1 ± 2.06 (at month 3) and 5.21 ± 1.71 (at month 6) that significantly were different from placebo-treated sides (9.77 ± 1.55 and 8.31 ± 1.88 at 3 and 6 months, respectively) (P value < 0.001 and < 0.001, respectively, for months 3 and 6). The subset analysis demonstrated a significant improvement in height (P value < 0.001 at 3 and 6 months), pliability (P value < 0.001 at 3 and 6 months), and vascularity (P value < 0.001 at 3 and 6 months) subsets at losartan compared to placebo-treated side. Losartan ointment was well tolerated with no complication. CONCLUSION: Losartan ointment successfully improved scar formation in mammoplasty and abdominoplasty patients. The losartan preventive effect should be confirmed in future large-scale studies with long-term follow-ups. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .


Assuntos
Abdominoplastia , Mamoplastia , Humanos , Feminino , Cicatriz/etiologia , Cicatriz/prevenção & controle , Cicatriz/patologia , Losartan/uso terapêutico , Losartan/farmacologia , Pomadas/farmacologia , Cicatrização , Resultado do Tratamento , Mamoplastia/métodos , Abdominoplastia/efeitos adversos , Angiotensinas/farmacologia
20.
Fitoterapia ; 159: 105197, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35439545

RESUMO

Pistacia vera oleoresin is one of the natural products used traditionally for the management of wounds. However, there were no scientific reports documented so far on the wound healing activities to substantiate the claim. This study assesses the potential of the oleoresin of P. vera collected in Italy and Algeria for wound healing efficacy via in vivo circular wound excision model. Italian and Algerian oleoresins were subjected to purification and successive fractionation to obtain three matrices. The fractions have been characterized using GC-FID and GC-MS analyses. Oleoresins mixed with vaseline (5% w/w) were topically applied on wound excision induced on the dorsum of rabbits. Wound healing effects were evaluated by percent of wound contraction. Biopsies performed after healing were histologically assessed. Phytochemical results showed a high content of terpenoids components inducing an efficient wound healing effect determined by an in vivo study. Italian and Algerian oleoresins ointments showed significant wound contraction from day 8 to day 16 as compared to the negative control. The two ointments have not showed statistically difference as compared to Cicatryl, reference drug. These results have also been confirmed by the histological evaluation of the tissues involved. The absence of signs of toxicity on the skin of rabbits indicated the safety of the ointments. The study showed that both oleoresins have a very high effectiveness as wound healing agents and appear to justify their traditional use in wound healing in several countries and offer a scientific support to the treatment of traditional healers.


Assuntos
Pistacia , Argélia , Animais , Estrutura Molecular , Pomadas/farmacologia , Pistacia/química , Extratos Vegetais/química , Coelhos , Resinas Vegetais/farmacologia , Pele , Cicatrização
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