RESUMEN

Skin inflammation associated with chronic diseases involves a direct role of keratinocytes in its immunopathogenesis, triggering a cascade of immune responses. Despite this, highly targeted treatments remain elusive, highlighting the need for more specific therapeutic strategies. In this study, nanocapsules containing quinizarin (QZ/NC) were developed and evaluated in an in vitro model of keratinocyte-mediated inflammation, incorporating the action of photodynamic therapy (PDT) and analyzing permeation in a 3D skin model. Comprehensive physicochemical, stability, cytotoxicity, and permeation analyses of the nanomaterials were conducted. The nanocapsules demonstrated desirable physicochemical properties, remained stable throughout the analysis period, and exhibited no spectroscopic alterations. Cytotoxicity tests revealed no toxicity at the lowest concentrations of QZ/NC. Permeation and cellular uptake studies confirmed QZ/NC permeation in 3D skin models, along with intracellular incorporation and internalization of the drug, thereby enhancing its efficacy in drug delivery. The developed model for inducing the inflammatory process in vitro yielded promising results, particularly when the synthesized nanomaterial was combined with PDT, showing a reduction in cytokine levels. These findings suggest a potential new therapeutic approach for treating inflammatory skin diseases.

RESUMEN

Dexamethasone has a high anti-inflammatory efficacy in treating skin inflammation. However, its use is related to the rebound effect, rosacea, purple, and increased blood glucose levels. Nanotechnology approaches have emerged as strategies for drug delivery due to their advantages in improving therapeutic effects. To reduce dexamethasone-related adverse effects and improve the anti-inflammatory efficacy of treatments, we developed nanocarriers containing this corticosteroid and oleic acid. Nanocapsules and nanoemulsion presented dexamethasone content close to the theoretical value and controlled dexamethasone release in an in vitro assay. Gellan gum-based hydrogels were successfully prepared to employ the nanostructured systems. A permeation study employing porcine skin showed that hydrogels containing non-nanoencapsulated dexamethasone (0.025%) plus oleic acid (3%) or oleic acid (3%) plus dexamethasone (0.025%)-loaded nanocapsules provided a higher amount of dexamethasone in the epidermis compared to non-nanoencapsulated dexamethasone (0.5%). Hydrogels containing oleic acid plus dexamethasone-loaded nanocapsules effectively inhibited mice ear edema (with inhibitions of 89.26 ± 3.77% and 85.11 ± 2.88%, respectively) and inflammatory cell infiltration (with inhibitions of 49.58 ± 4.29% and 27.60 ± 11.70%, respectively). Importantly, the dexamethasone dose employed in hydrogels containing the nanocapsules that effectively inhibited ear edema and cell infiltration was 20-fold lower (0.025%) than that of non-nanoencapsulated dexamethasone (0.5%). Additionally, no adverse effects were observed in preliminary toxicity tests. Our study suggests that nanostructured hydrogel containing a reduced effective dose of dexamethasone could be a promising therapeutic alternative to treat inflammatory disorders with reduced or absent adverse effects. Additionally, testing our formulation in a clinical study on patients with skin inflammatory diseases would be very important to validate our study.

RESUMEN

The eyes provide themselves with immune tolerance. Frequent skin inflammatory diseases in young blind people suggest, nonetheless, that the eyes instruct a systemic immune tolerance that benefits the whole body. We tested this premise by using delayed skin contact hypersensitivity (DSCH) as a tool to compare the inflammatory response developed by sighted (S) and birth-enucleated (BE) mice against oxazolone or dinitrofluorobenzene at the ages of 10, 30 and 60 days of life. Adult mice enucleated (AE) at 60 days of age were also assessed when they reached 120 days of life. BE mice displayed exacerbated DSCH at 60 but not at 10 or 30 days of age. AE mice, in contrast, show no exacerbated DSCH. Skin inflammation in 60-day-old BE mice was hapten exclusive and supported by distinct CD8+ lymphocytes. The number of intraepidermal T lymphocytes and migrating Langerhans cells was, however, similar between S and BE mice by the age of 60 days. Our observations support the idea that the eyes instruct systemic immune tolerance that benefits organs outside the eyes from an early age. The higher prevalence of inflammatory skin disorders reported in young people might then reflect reduced immune tolerance associated with the impaired functional morphology of the eyes.

RESUMEN

Essential oils are a complex mixture of aromatic substances whose pharmacological actions, including antimicrobial, antioxidant, anticancer, and anti-inflammatory activities, have been widely reported. This study aimed to evaluate the anti-Candida and dermal anti-inflammatory activity of essential oils from native and cultivated Ecuadorian plants. Essential oils from Bursera graveolens, Dacryodes peruviana, Mespilodaphne quixos, and Melaleuca armillaris were isolated by hydrodistillation and were characterized physically and chemically. Its tolerance was analyzed by in vitro and in vivo studies. The antifungal activity was studied against Candida albicans, Candida glabrata, and Candida parapsilosis, whereas the anti-inflammatory effect was evaluated by a mouse ear edema model. The main compounds were limonene, α-phellandrene, (E)-methyl cinnamate, and 1,8-cineole, respectively. All essential oils showed high tolerability for skin application, antifungal activity against the three Candida strains, and anti-inflammatory efficacy by decreasing edema and overexpression of pro-inflammatory cytokines. Dacryodes peruviana essential oil showed the highest antifungal activity. On the other hand, Dacryodes peruviana and Melaleuca armillaris showed the greatest anti-inflammatory potential, decreasing edema by 53.3% and 65.25%, respectively, and inhibiting the overexpression of TNF-α, IL-8, IL-17A, and IL-23. The results suggest that these essential oils could be used as alternative therapies in the treatment of both cutaneous candidiasis and dermal inflammation.

Asunto(s)

Candidiasis , Aceites Volátiles , Ratones , Animales , Aceites Volátiles/química , Antifúngicos/química , Aceites de Plantas/química , Ecuador , Candida , Candida albicans , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Antiinflamatorios/farmacología , Pruebas de Sensibilidad Microbiana

RESUMEN

Psoriasis is immune-mediated skin disorder affecting thousands of people. Sphingolipids (SLs) are bioactive molecules present in the epidermis, involved in the following cellular processes: proliferation, differentiation, and apoptosis of keratinocytes. Alterations in SLs synthesis have been observed in psoriatic skin. To investigate if the imbalance in lipid skin metabolism could be related to psoriasis, we analyzed the gene expression in non-lesioned and lesioned skin of patients with psoriasis available in two datasets (GSE161683 and GSE136757) obtained from National Center for Biotechnology Information (NCBI). The differentially expressed genes (DEGs) were searched for using NCBI analysis, and Gene Ontology (GO) biological process analyses were performed using the Database of Annotation, Visualization, and Integrated Discovery (DAVID) platform. Venn diagrams were done with InteractiVenn tool and heatmaps were constructed using Morpheus software. We observed that the gene expression of cytoplasmic phospholipase A2 (PLA2G4D), glycerophosphodiester phosphodiesterase domain containing 3 (GDP3), arachidonate 12-lipoxygenase R type (ALOX12B), phospholipase B-like 1 (PLBD1), sphingomyelin phosphodiesterase 3 (SMPD3), ganglioside GM2 activator (GM2A), and serine palmitoyltransferase long chain subunit 2 (SPTLC2) was up-regulated in lesioned skin psoriasis when compared with the non-lesioned skin. These genes are related to lipid metabolism and more specifically to sphingolipids. So, in the present study, the role of sphingolipids in psoriasis pathogenesis is summarized. These genes could be used as prognostic biomarkers of psoriasis and could be targets for the treatment of patients who suffer from the disease.

RESUMEN

Canine atopic dermatitis (cAD) is a worldwide allergic skin disease. The affected dog population can show different clinical patterns according to geographic region, and a lack of studies in Brazil is observed. Therefore, the aim of the present study was to assess the clinical and epidemiological data of cAD in dogs treated in a private clinical practice in Fortaleza, a city located in the Northeast Region of Brazil. cAD was diagnosed in 35% of dogs, being Shih-tzu and Poodle the most affected breeds. Paws and ears were frequently injured sites. Almost 50% of atopic dogs were diagnosed with superficial pyoderma and 36% with cutaneous malasseziosis. Atopic dogs with outdoor habits were less likely to develop cutaneous malassezial infection, and with routine ear, cleaning habits were less likely to develop bacterial otitis externa. In conclusion, canine atopic dermatitis is a prevalent disease in private clinical practice in Fortaleza, and lifestyle habits can be considered a risk factor for cutaneous malasseziosis infection and bacterial otitis externa in atopic dogs.

---

A dermatite atópica canina (DAC) é uma doença alérgica cutânea de ocorrência mundial. A população canina acometida pode apresentar diferentes padrões clínicos de acordo com a região geográfica e observa-se uma carência de estudos no Brasil. Portanto, o objetivo do presente estudo é avaliar os dados clínicos e epidemiológicos da DAC em cães atendidos em uma clínica privada em Fortaleza, cidade localizada na Região Nordeste do Brasil. A DAC foi diagnosticada em 35% dos cães, sendo Shih-tzu e Poodle as raças mais acometidas. As patas e as orelhas foram locais frequentemente afetados. Quase 50% dos cães atópicos foram diagnosticados com piodermite superficial e 36% com malasseziose cutânea. Cães atópicos com hábitos ao ar livre foram menos propensos a desenvolver malasseziose cutânea e com hábitos rotineiros de limpeza auricular foram menos propensos a desenvolver otite externa bacteriana. Em conclusão, a dermatite atópica canina é uma doença prevalente na prática clínica privada em Fortaleza e os hábitos de vida podem ser considerados como um fator de risco para infecção por malasseziose cutânea e otite externa bacteriana em cães atópicos.

Asunto(s)

Animales , Perros , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/patología , Dermatitis Atópica/veterinaria , Dermatitis Atópica/epidemiología , Enfermedades de los Perros , Otitis Externa/veterinaria , Brasil/epidemiología

RESUMEN

Although rosacea is classically considered a skin disorder, recent evidence shows that it is emerging as a systemic disease. The classical symptoms of burning, intense erythema, and flushing could be related to several systemic and metabolic comorbidities. We highlight the role of sleep disturbance as a possible trigger for rosacea, which could be explained by the inflammatory and stressful conditions that can be produced by poor sleep. In particular, we call attention to obstructive sleep apnea (OSA), a common multisystemic sleep disorder; it could be linked with rosacea in the context of the metabolic syndrome, which in turn is frequently associated with OSA. Obstructive sleep apnea may be accompanied by autonomic system activation and catecholamine release, which can aggravate rosacea. Poor sleep, resulting from any underlying cause, can have a range of effects including immunological modulation and intrinsic cutaneous changes (such as the impairment of skin barrier defense and modifications in the skin microbiome) that may trigger rosacea. Further studies on this subject could provide more evidence on these relationships and help to improve the patients' quality of life and management of this uncomfortable and potentially severe skin condition.

Asunto(s)

Rosácea , Apnea Obstructiva del Sueño , Humanos , Calidad del Sueño , Calidad de Vida , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Rosácea/complicaciones , Comorbilidad

RESUMEN

Previously, we isolated lactic acid bacteria from the slime of the garden snail Helix aspersa Müller and selected Weissella viridescens UCO-SMC3 because of its ability to inhibit in vitro the growth of the skin-associated pathogen Cutibacterium acnes. The present study aimed to characterize the antimicrobial and immunomodulatory properties of W. viridescens UCO-SMC3 and to demonstrate its beneficial effect in the treatment of acne vulgaris. Our in vitro studies showed that the UCO-SMC3 strain resists adverse gastrointestinal conditions, inhibits the growth of clinical isolates of C. acnes, and reduces the adhesion of the pathogen to keratinocytes. Furthermore, in vivo studies in a mice model of C. acnes infection demonstrated that W. viridescens UCO-SMC3 beneficially modulates the immune response against the skin pathogen. Both the oral and topical administration of the UCO-SCM3 strain was capable of reducing the replication of C. acnes in skin lesions and beneficially modulating the inflammatory response. Of note, orally administered W. viridescens UCO-SMC3 induced more remarkable changes in the immune response to C. acnes than the topical treatment. However, the topical administration of W. viridescens UCO-SMC3 was more efficient than the oral treatment to reduce pathogen bacterial loads in the skin, and effects probably related to its ability to inhibit and antagonize the adhesion of C. acnes. Furthermore, a pilot study in acne volunteers demonstrated the capacity of a facial cream containing the UCO-SMC3 strain to reduce acne lesions. The results presented here encourage further mechanistic and clinical investigations to characterize W. viridescens UCO-SMC3 as a probiotic for acne vulgaris treatment.

RESUMEN

Galectin-9 (Gal-9) is a beta-galactoside-binding protein with a variety of biological functions related to immune response. However, in allergic diseases, its mechanism of action is not fully understood. This study evaluates the expression pattern of Gal-9 in patients with atopic dermatitis (AD), in ovalbumin (OVA)-induced experimental atopic dermatitis (AD) in mice, as well as its effect on human keratinocytes. The skin of OVA-immunized BALB/c mice was challenged with drops containing OVA on days 11, 14-18, and 21-24. HaCaT cells were cultured in the following experimental conditions: control (growth medium only) or stimulated with TNF-α/IFN-γ, or IL-4, or IL-17 with or without Gal-9 treatment. AD was characterized by increased levels of Gal-9 in mouse and human skin, especially in the epidermis, and with a marked influx of Gal-9 positive eosinophils and mast cells compared to the control group. Gal-9 showed an immunomodulatory effect on keratinocytes by decreasing the release of IL-6 by IL-4-stimulated keratinocytes or increasing the IL-6 and RANTES levels by IL-17- or TNF-α/IFN-γ-stimulated cells, respectively. Under IL-17, Gal-9 treatment also altered the proliferation rate of cells. Overall, increased levels of Gal-9 in AD skin contribute to the control of inflammatory response and the proliferative process of keratinocytes, suggesting this lectin as a relevant therapeutic target.

Asunto(s)

Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Galectinas/metabolismo , Queratinocitos/metabolismo , Queratinocitos/patología , Animales , Movimiento Celular , Proliferación Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Inflamación/patología , Masculino , Ratones Endogámicos BALB C , Piel/patología , Regulación hacia Arriba/genética

RESUMEN

Allergic contact dermatitis (ACD) is a common allergic skin disease that affects individuals subjected to different antigen exposure conditions and significantly impacts the quality of life of those affected. Numerous studies have demonstrated that probiotics suppress inflammation through immunomodulatory effects. In this study, we aimed to evaluate the effect of the probiotic Bifidobacterium longum 51A as a preventive treatment for ACD using an oxazolone-induced murine model. We demonstrated that B. longum 51A exerted a prophylactic effect on oxazolone-induced ACD-like skin inflammation via reductions in ear and dermal thickness and leucocyte infiltration. The administration of inactivated B. longum 51A did not affect oxazolone-induced ACD-like skin inflammation, suggesting that the bacteria must be alive to be effective. Given that B. longum 51A is an acetate producer, we treated mice with acetate intraperitoneally, which also prevented ear and dermal thickening. Moreover, the tissue levels of the inflammatory cytokines and chemokines interleukin (IL)-10, IL-33, tumour necrosis factor-α, chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 and chemokine (C-C motif) ligand 5/RANTES were significantly reduced after probiotic treatment, but only IL-33 and IL-10 were reduced when the mice were treated with acetate. These results show that B. longum 51A exerted a potential prophylactic effect on skin inflammation and that acetate represents one potential mechanism. However, other factors are likely involved since these two treatments do not yield the same results.

Asunto(s)

Bifidobacterium longum/fisiología , Dermatitis Alérgica por Contacto/inmunología , Dermatitis Alérgica por Contacto/prevención & control , Probióticos/administración & dosificación , Animales , Citocinas/genética , Citocinas/inmunología , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/genética , Femenino , Humanos , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-33/genética , Interleucina-33/inmunología , Ratones , Ratones Endogámicos BALB C , Oxazolona/efectos adversos , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Cutaneous inflammatory diseases, such as irritant contact dermatitis, are usually treated with topical corticosteroids, which cause systemic and local adverse effects limiting their use. Thus, the discovery of new therapeutic alternatives able to effectively treat skin inflammatory disorders, without causing adverse effects, is urgently needed. AIM OF THE STUDY: To investigate the topical anti-inflammatory effect of oleic acid (OA), a monounsaturated fatty acid, into Pemulen® TR2-based semisolid dosage forms, employing a croton oil-induced irritant contact dermatitis model in mice. MATERIALS AND METHODS: Male Swiss mice were submitted to skin inflammation protocols by acute and repeated applications of croton oil. The anti-inflammatory activity of Pemulen® TR2 hydrogels containing OA was evaluated by assessing oedema, inflammatory cell infiltration, and pro-inflammatory cytokine IL-1ß levels. The mechanisms of action of OA were evaluated using cytokine IL-1ß application or pretreatment with the glucocorticoid antagonist mifepristone. Possible toxic effects of OA were also assessed. RESULTS: Pemulen® TR2 3% OA inhibited the acute ear oedema [maximal inhibition (Imax) = 76.41 ± 5.69%], similarly to dexamethasone (Imax = 84.94 ± 2.16%), and also inhibited ear oedema after repeated croton oil application with Imax = 85.75 ± 3.08%, similar to dexamethasone (Imax = 81.03 ± 4.66%) on the day 7 of the experiment. Croton oil increased myeloperoxidase activity, which was inhibited by Pemulen® TR2 3% OA (Imax = 71.37 ± 10.97%) and by 0.5% dexamethasone (Imax = 96.31 ± 3.73%). Pemulen® TR2 3% OA also prevented the increase in pro-inflammatory cytokine IL-1ß levels induced by croton oil (Imax = 94.18 ± 12.03%), similar to 0.5% dexamethasone (Imax = 87.21 ± 10.58%). Besides, both Pemulen® TR2 3% OA and 0.5% dexamethasone inhibited IL-1ß-induced ear oedema with an Imax of 80.58 ± 2.45% and 77.46 ± 1.92%, respectively. OA and dexamethasone anti-inflammatory effects were prevented by 100% and 91.43 ± 5.43%, respectively, after pretreatment with mifepristone. No adverse effects were related to Pemulen® TR2 3% OA administration. CONCLUSIONS: OA demonstrated anti-inflammatory efficacy similar to dexamethasone, clinically used to treat skin inflammatory conditions, without presenting adverse effects.

Asunto(s)

Antiinflamatorios/farmacología , Dermatitis Irritante/prevención & control , Ácido Oléico/farmacología , Piel/efectos de los fármacos , Administración Cutánea , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/toxicidad , Aceite de Crotón , Dermatitis Irritante/etiología , Dermatitis Irritante/metabolismo , Dermatitis Irritante/patología , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Masculino , Ratones , Ácido Oléico/administración & dosificación , Ácido Oléico/toxicidad , Piel/metabolismo , Piel/patología

RESUMEN

Annona muricata L. is used in folk medicine for treatment of diseases related to inflammatory and oxidative processes. This study investigated the effect of the aqueous extract of A. muricata leaves (AEAM) on TPA-induced ear inflammation and antioxidant capacity, both in vitro and in vivo. The in vitro antioxidant capacity of AEAM was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing/antioxidant power (FRAP) and lipoperoxidation assays. Cytotoxicity and reactive oxygen species (ROS) release were evaluated in the L929 fibroblasts. Swiss mice were submitted to TPA application and were topically treated with AEAM (0.3, 1 or 3 mg/ear). After 6 h, inflammatory and oxidative parameters were evaluated. Quercetin 3-glucoside, rutin, chlorogenic acid, catechin and gallic acid were identified in AEAM. It also presented antioxidant activity in all in vitro assays used. Incubation with AEAM did not cause cell cytotoxicity but reduced ROS release from fibroblasts. Compared with the control group, treatment with AEAM significantly reduced ear oedema and mieloperoxidase activity in inflamed ears, as well as histological parameters of inflammation. These results were associated with the reduction of total hydroperoxides and modulation of catalase, but not superoxide dismutase activity. These findings show the anti-inflammatory effect of AEAM is associated with antioxidant capacity.

Asunto(s)

Annona/química , Antioxidantes/farmacología , Inflamación/tratamiento farmacológico , Extractos Vegetales/farmacología , Administración Cutánea , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/aislamiento & purificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/patología , Inflamación/patología , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Hojas de la Planta , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

In this study, we developed a water-in-oil microemulsion containing vitamin A (retinol) and vitamin E (α-tocopherol), which serves as a multifunctional nanosystem that co-delivers antioxidants and displayed additive effect against acute skin inflammation. Microemulsion (ME) was prepared by mixing a surfactant blend (Tween 80 and propylene glycol, 5:1) with isopropyl myristate and water (ratio of 50:40:10, respectively). Vitamin A (0.05% w/w concentration) and/or vitamin E (0.1% w/w concentration) were incorporated into the surfactant mixture of ME by stirring with a magnetic stirrer for 30 min. This multifunctional ME displayed physical stability, with low cytotoxicity in 3T3 cell line, as well as cellular internalization into the cytosol. In vivo treatments using ME delivering α-tocopherol reduced dermal expression of TNF-α by 1.3-fold (p < 0.01), when compared to unloaded ME treatment group. When retinol was added into the ME containing α-tocopherol, it further reduced TNF-α expression by 2-fold (p < 0.001), suggesting the additive effect of vitamin E and vitamin A in the treatment against skin inflammation. In conclusion, we successfully developed the use of water-in-oil ME to pack both vitamin E and vitamin A, and demonstrated for the first time its anti-inflammatory potential when applied topically to TPA-induced inflamed skin.

Asunto(s)

Sistemas de Liberación de Medicamentos , Inflamación/tratamiento farmacológico , Inflamación/patología , Piel/patología , Vitamina A/administración & dosificación , Vitamina E/administración & dosificación , Enfermedad Aguda , Administración Tópica , Animales , Rastreo Diferencial de Calorimetría , Supervivencia Celular/efectos de los fármacos , Emulsiones , Células HaCaT , Humanos , Ratones , Ratones Pelados , Células 3T3 NIH , Piel/efectos de los fármacos , Porcinos , Vitamina A/farmacología , Vitamina A/uso terapéutico , Vitamina E/farmacología , Vitamina E/uso terapéutico

RESUMEN

The treatment of cutaneous inflammation with topical corticosteroids may cause adverse effects reinforcing the need for therapeutic alternatives to treat inflammatory skin disorders. We investigated the anti-inflammatory effect of oleic acid (OA), a fatty acid of the omega-9 (ω-9) family, and we point out it as an alternative to treat inflammatory skin disorders. OA was incorporated into Lanette®- or Pemulen® TR2-based semisolid preparations and the pH, spreadability, rheological behavior and in vivo anti-inflammatory performance in a UVB radiation-induced skin inflammation model in mice were assessed. The anti-inflammatory activity was verified after single or repeated treatment of the mouse ear following the UVB. The OA action on glucocorticoid receptors was investigated. Both semisolids presented pH values compatible with the deeper skin layers, appropriate spreadability factors, and non-Newtonian pseudoplastic rheological behavior. Pemulen® 3% OA inhibited ear edema with superior efficacy than Lanette® 3% OA and dexamethasone after a single treatment. Pemulen® 3% OA and dexamethasone also reduced inflammatory cell infiltration. After repeated treatments, all formulations decreased the ear edema at 24 h, 48 h and 72 h after UVB. OA in semisolids, especially Pemulen® TR2-based ones, presented suitable characteristics for cutaneous administration and its anti-inflammatory activity seems to occur via glucocorticoid receptors. OA was also capable to reduce croton oil-induced skin inflammation. Besides, the ex vivo skin permeation study indicated that OA reaches the receptor medium, which correlates with a systemic absorption in vivo. The natural compound OA could represent a promising alternative to those available to treat inflammatory skin disorders.

Asunto(s)

Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Ácido Oléico/farmacología , Receptores de Glucocorticoides/metabolismo , Piel/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Administración Cutánea , Animales , Dermatitis/tratamiento farmacológico , Dermatitis/metabolismo , Edema/tratamiento farmacológico , Edema/metabolismo , Inflamación/metabolismo , Masculino , Ratones , Piel/metabolismo

RESUMEN

BACKGROUND: Topical corticosteroids have been the most commonly prescribed drugs to treat skin inflammation, but their uses can lead to several adverse effects. Nowadays, new pharmacological strategies have been evaluated to improve dermatologic efficacy and reduce adverse effects, including natural products. OBJECTIVES: The aim of this study was to evaluate and compare the effects of a plant sterol standardized supercritical CO2 phytopharmaceutical of Physalis angulata L. with hydrocortisone on the immune and inflammatory mediators, and skin repair components production. Moreover, we studied effects of both products on the skin microcirculation and temperature in a double-blind placebo-controlled clinical trial. METHODS: Both products were evaluated on the immune (IL-6, IL-10, INF-γ, TNF-α, and IL-1α), inflammatory (COX-2, LOX, PLA2 , PGE2 , LTB4 , histamine, and NF-κB), and repair components (TGF-ß, GM-CSF, collagen, and GAG) production on human keratinocytes and fibroblast in non-stimulated and LPS-stimulated conditions. Indeed, in a randomized double-blind placebo-controlled clinical trial, we evaluated the effects of the both creams on the skin microcirculation and temperature using laser Doppler and infrared thermometer, respectively. RESULTS: Physalis angulata acted on the skin, modulating immune status and inflammatory response producing corticoid-like effects, but different of hydrocortisone, increased skin repair factors. The effects of phytopharmaceutical cream in the clinical trial promoted a better reduction in skin microcirculation and temperature than hydrocortisone. CONCLUSIONS: Taken together, the results indicate that sterol standardized CO2 supercritical preparation of P angulata is a new and innovative phytopharmaceutical with multiple pharmacological effects potentially useful as human skin protective product, particularly against cutaneous inflammatory disorders.

RESUMEN

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and particularly selective cyclooxygenase-2 (COX-2) inhibitors such as celecoxib (Cxb) are considered promising cancer chemopreventive for colon, breast, prostate, lung, and skin cancers. However, the clinical application to the prevention is limited by concerns about safety, potential to serious toxicity (mainly for healthy individuals), efficacy and optimal treatment regimen. Cxb exhibits advantages as potent antiinflammatory and gastrointestinal tolerance compared with conventional NSAID's. Recent researches suggest that dermatological formulations of Cxb are more suitable than oral administration in the treatment of cutaneous disease, including skin cancer. To date, optimism has been growing regarding the exploration of the topical application of Cxb (in the prevention of skin cancers and treatment of cutaneous inflammation) or transdermal route reducing risks of systemic side effects. OBJECTIVE: This paper briefly summarizes our current knowledge of the development of the cutaneous formulations or delivery systems for Cxb as anti-inflammatory drug (for topical or transdermal application) as well its chemopreventive properties focused on skin cancer. CONCLUSION: New perspectives emerge from the growing knowledge, bringing innovative techniques combining the action of Cxb with other substances or agents which act in a different way, but complementary, increasing the efficacy and minimizing toxicity.

Asunto(s)

Antiinflamatorios no Esteroideos/uso terapéutico , Celecoxib/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Dermatitis/tratamiento farmacológico , Dermatitis/prevención & control , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/prevención & control , Administración Cutánea , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Celecoxib/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Humanos , Ratones , Modelos Animales , Ratas

RESUMEN

Albumin is a natural, biocompatible, biodegradable and nontoxic polymer and due to these features, nanoparticles made of albumin are a good system for drug or antigen delivery. Polymeric nanoparticles are being widely explored as new vaccines platforms due to the capacity of those nanoparticles to prime the immune system by providing sustained release of the antigen after injection. Biodegradable nanoparticles associated with proteins represent a promising method for in vivo delivery of vaccines. In our previous studies, bovine serum albumin nanoparticles (BSA-NPs) were identified as a promising system for in vivo delivery of microbial antigens. The aim of this work was to show the effect of BSA-NPs on skin after nanoparticles administration. The pro-inflammatory activity of BSA-NPs was evaluated using in vivo models. BSA-NPs are easily uptake by macrophagic RAW 264.7 and BHK-21 cells without any significant cytotoxicity. Histological examination of skin sections from BSA-NPs-treated mice revealed intense cellular infiltration, increased skin thickness, follicular hypertrophy, vascular congestion and marked collagenesis. Mice immunized with recombinant non-structural protein 1 (rNS1) from Dengue virus 1 and BSA-NPs showed a high seroconversion rate if compared to animals immunized only with rNS1. Therefore, the effect of BSA-NPs on skin after BSA-NPs administration has a biotechnological relevance to the rational design of vaccine formulations based on albumin nanocarriers. However in the next years future studies should be carried out to best characterize the effect of BSA-NPs on dendritic cells and establish the role of these nanoparticles as a new vaccine platform for infectious diseases or cancer.

Asunto(s)

Portadores de Fármacos/toxicidad , Nanopartículas/toxicidad , Albúmina Sérica Bovina/toxicidad , Piel/efectos de los fármacos , Vacunas/administración & dosificación , Animales , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/administración & dosificación , Femenino , Inyecciones Subcutáneas , Ratones , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Células RAW 264.7 , Seroconversión , Albúmina Sérica Bovina/administración & dosificación , Piel/inmunología , Piel/patología , Propiedades de Superficie , Vacunas/inmunología , Proteínas no Estructurales Virales/administración & dosificación , Proteínas no Estructurales Virales/inmunología

RESUMEN

The aim of this study was to evaluate the anti-edematogenic activity of X. americana L. (HEXA) hydroethanolic extract in ear edema models (acute and chronic) induced by croton oil and by different phlogistic agents (arachidonic acid, capsaicin, phenol and histamine), identifying the possible anti-edematogenic mechanism. HEXA demonstrated a significant anti-edematogenic effect at concentrations of 100-500 µg/ear in ear edema induced by croton oil with higher inhibition of edema of 39.37. However, the concentrations of 100 and 200 µg/ear were taken as a standard, demonstrating the effect in the chronic model induced by croton oil with inhibition of 61.62% and 48.74%. In the AA-induced ear edema model, HEXA showed inhibition of: 24.45% and 32.31%; capsaicin inhibition of 72.72% and 47.57%; phenol inhibition of 34% and 20.1%; and histamine inhibition of 31.8% and 21.62%. Then, the results were showed that HEXA demonstrated an anti-edematogenic effect in acute and chronic inflammation models, demonstrating a probable mechanism of action by the inhibition or modulation of key mediators of the inflammatory process. The chemical profile and presence of flavonoids guaranteeing a profile of activity similar to natural drugs that act or modulate the production of mediators of inflammations.

Asunto(s)

Cromatografía Líquida de Alta Presión/métodos , Dermatitis/tratamiento farmacológico , Edema/tratamiento farmacológico , Olacaceae/química , Extractos Vegetales/uso terapéutico , Animales , Ácido Araquidónico/efectos adversos , Ácido Araquidónico/antagonistas & inhibidores , Capsaicina/efectos adversos , Capsaicina/antagonistas & inhibidores , Aceite de Crotón/toxicidad , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Femenino , Histamina/efectos adversos , Antagonistas de los Receptores Histamínicos/uso terapéutico , Ratones , Fenol/efectos adversos , Fenol/antagonistas & inhibidores

RESUMEN

OBJECTIVES: This study aimed to evaluate the chronic topical anti-inflammatory activity of the pharmaceutical formulation ProHLP containing the hexane fraction of Lacistema pubescens (HLP). It was also investigated the possible cutaneous and systemic adverse effects of HLP and ProHLP in mice when compared to dexamethasone. METHODS: The chronic topical anti-inflammatory activity was determined by croton oil multiple application-induced mouse ear oedema model. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Cutaneous atrophy induced by HLP and topical glucocorticoid treatments and excision skin wounds model to evidenced possible adverse reactions were also determined. KEY FINDINGS: ProHLP significantly reduced the mice ear oedema and considerably accelerated the wound-healing process. Also, HLP did not lead cutaneous atrophy and preserved the clinical aspect of the thymus, adrenal and spleen, unlike dexamethasone. CONCLUSIONS: The results suggested that ProHLP is an efficient and safer pharmaceutical formulation to treat chronic inflammatory diseases.

Asunto(s)

Antiinflamatorios/administración & dosificación , Dexametasona/administración & dosificación , Modelos Animales de Enfermedad , Edema/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Administración Tópica , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/patología , Animales , Antiinflamatorios/efectos adversos , Antiinflamatorios/aislamiento & purificación , Enfermedad Crónica , Dermatitis/tratamiento farmacológico , Dermatitis/patología , Dexametasona/efectos adversos , Edema/patología , Masculino , Ratones , Extractos Vegetales/efectos adversos , Extractos Vegetales/aislamiento & purificación , Timo/efectos de los fármacos , Timo/patología , Resultado del Tratamiento

RESUMEN

Atopic dermatitis (AD) is caused by both dysregulated immune responses and an impaired skin barrier. Although beta-galactoside-binding protein galectin-1 (Gal-1) has immunomodulatory effects in several inflammatory disorders, therapeutic strategies based on its anti-inflammatory properties have not been explored in AD. Thus, we evaluate pharmacological treatment with Gal-1 in the progression of an ovalbumin (OVA)-induced AD-like skin lesions. The skin of OVA-immunized male BALB/c mice was challenged with drops containing OVA on days 11, 14-18 and 21-24. Additionally, in the last week, a subset of animals was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). Treatment with rGal-1 decreased the clinical signs of dermatitis in BALB/c mice and diminished local eotaxin and IFN-γ levels. The treatment also suppressed the infiltration of eosinophils and mast cells, which was verified by reduced expression of mouse mast cell protease 6 (mMCP6) and eosinophil peroxidase (EPX). These localized effects are associated with extracellular signal-regulated kinase (ERK) activation and downregulation of endogenous Gal-1. The inhibition of disease progression induced by rGal-1 was also correlated with reduced plasma IL-17 levels. Our results demonstrate that rGal-1 is an effective treatment for allergic skin inflammation in AD and may impact the development of novel strategies for skin inflammatory diseases. KEY MESSAGES: Pharmacological treatment with rGal-1 reduces clinical signs of atopic dermatitis. Systemic treatment with rGal-1 inhibits eosinophil and mast cell influx in the skin of AD animals. rGal-1 reduced local eotaxin levels and systemic IL-17 levels. The inhibition of disease progression induced by rGal-1 was correlated with upregulation of phosphorylated ERK.

Asunto(s)

Dermatitis Atópica/metabolismo , Galectina 1/metabolismo , Animales , Antiinflamatorios/farmacología , Biopsia , Citocinas/metabolismo , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Dermatitis Atópica/terapia , Modelos Animales de Enfermedad , Galectina 1/genética , Galectina 1/farmacología , Expresión Génica , Inmunidad/efectos de los fármacos , Inmunoglobulina E/inmunología , Inmunomodulación/efectos de los fármacos , Recuento de Leucocitos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Fenotipo