Dry Skin Conditions Research Articles

How to Choose an Emollient? Pharmaceutical and sensory attributes for product selection.

Emollients are part of daily body care and have become indispensable therapeutic adjuvants for the treatment of dry skin conditions. Adherence to topical treatments, notably for dry skin conditions, has been reported to be low. The underlying reasons may include insufficient medical and nursing support for product selection, specific product attributes, aspects of product application, and product feel on the skin. Attempts have also been made to portray lipid content, galenic product format, or rheological attributes (pharmaceutical attributes) as adherence-promoting or adherence-preventing properties. In the treatment of dry dermatoses with emollients, there is little information describing and relating to these various features. We explored whether the sensory attributes of selected emollients were associated with common product attributes such as lipid content, viscosity, or galenic product format, and discuss the extent to which this information is useful for product selection. Nine trained panellists evaluated ten selected emollients based on a set of 18 predefined sensory attributes according to a standard guide for sensory descriptive analysis. Viscosity was determined using a rotational rheometer. The emollients had product-specific sensory attributes. Lipid content, viscosity, and galenic product format are not generally indicative of sensory product attributes. Contrary to popular belief, lipid content and viscosity are not generally indicative of sensory product attributes. This is mainly due to the different physicochemical properties of the lipid phase ingredients, which are product-specific and diverse. As most emollients contain significant amounts of volatile ingredients that evaporate during and after application, their galenic format changes dramatically. Therefore, this is not a viable selection criterion. Because refined information on sensory product attributes, as compiled for this study, is rarely available in everyday life, eliciting individual and subjective patient preferences through dialogue remains crucial. Ideally, patient preferences can be elicited from the sample packs.

Effects of a pH-Regulating Emollient Cream in Mild Atopic Dermatitis Patients with Moderate Localized Lesions

Introduction: Increased skin pH values in patients with atopic dermatitis (AD) contribute to poor antimicrobial and permeability barrier functions of the skin. In practice, the majority of topical preparations available for dry skin conditions do not provide sufficient pH and buffering capacity for maintaining optimum skin surface conditions. To address this issue, we tested a novel zinc lactobionate preparation to determine whether the regular application would lower skin surface pH, and in doing so improve the condition of lesional skin. Methods: The assessment for local severity of AD was done with the Scoring Atopic Dermatitis Index (SCORAD) and skin dryness was assessed by capacitance measurement. Results: The results showed that the test product lowered skin pH and improved AD skin lesions from moderate to mild during 2 weeks of application. In the treated area a lowered pH of about 0.85 units was found. Together with the lowering of pH, the local SCORAD significantly improved from 8.3 on average down to 4.0, while in the untreated area, only a slight improvement (from 8.2 to 6.4) was found. Conclusion: Synergistic effects of the test product’s pH lowering and emollient properties might explain the observed improvements in clinical signs of AD and further research against a comparator would allow the specific contribution of pH modulation to these improvements to be unambiguously isolated.

Overexpression of the β-Subunit of Acid Ceramidase in the Epidermis of Mice Provokes Atopic Dermatitis-like Skin Symptoms.

We previously reported that a pathogenic abnormality in the barrier and water-holding functions of the stratum corneum (SC) in the skin of patients with atopic dermatitis (AD) is mainly attributable to significantly decreased levels of total ceramides in the SC. That decrease is mediated by the abnormal expression of a novel ceramide-reducing enzyme, sphingomyelin/glucosylceramide deacylase (SGDase), which is the β-subunit (ASAH1b) of acid ceramidase. In this study, we determined whether mice overexpressing ASAH1b in their epidermis develop AD-like skin symptoms. We generated transgenic (TG) mice overexpressing ASAH1b, regulated by the involucrin promoter, to localize its expression in the upper epidermis. After hair removal using a depilatory cream containing glycolic acid, the TG mice without any visible skin inflammation at 8 weeks of age had increased levels of ASAH1b and decreased levels of SC ceramide, with disrupted barrier functions measured by trans-epidermal water loss compared to the wild-type (WT) mice. Interestingly, enzymatic assays revealed that SGDase activity was not detectable in the skin of the TG mice compared to WT mice. Immunological staining revealed that there was an increased expression level of IL-33 in the epidermis and an accumulation of macrophages in the dermis of TG mice compared to WT mice, which are phenotypic characteristics of AD, that were exacerbated by tape-stripping of the skin. In the skin of the TG mice, the mRNA levels of IL-5, CCL11, IL-22, CXCL10, and IFNγ were significantly upregulated compared to the WT mice, and tape-stripping significantly increased the mRNA levels of IL-4, IL-33, CXCL1, CXCL12, TLR9, and CD163 compared to WT mice. These findings strongly indicate that the skin of the depilatory cream-treated TG mice exists in an atopic dry skin condition that is highly sensitive to various environmental stimuli. The sum of our results suggests that ASAH1b itself, even in the absence of its enzymatic activity, is a major etiologic factor for atopic dry skin symptoms via an unknown mechanism.

Evaluating the effect of moisturizers containing endogenous lipids on skin barrier properties

Lipids in stratum corneum are largely responsible for skin barrier function. There have been numerous studies on skin barrier repairing and moisturizing effects of products containing occlusives, emollients and humectants. However, currently there are few studies systematically evaluating effect of moisturizers containing endogenous lipids on skin barrier properties. The objective of this study was to study the effect of products containing endogenous lipids on various barrier-related indicators. A total 89 subjects with dry skin were enrolled. To evaluate the effect of the test products on skin barrier function and hydration after 28 days of use on the face, this study combined clinical assessments of skin condition (skin redness, global appearance of dry line, skin roughness and radiance), instrumental assessments (transepidermal water loss, skin hydration and scaliness) and photo tracking (VISIA-CR,VC20 and 3D in-vivo Reflectance Confocal Microscope). Adverse reactions were also assessed. All test products showed significant improvement in all the attributes assessed by both clinical assessments and instrumental assessments after 28 days of treatment. In addition, the products containing skin-identical ceramides and niacinamide show improvement on TEWL and skin hydration. Two products containing exogenous lipids can improve skin hydration and barrier function which have demonstrated efficacy in improving dry skin condition.

Delivery of small hydrophilic molecules across the stratum corneum: Identification of model systems and parameters to study topical delivery of free amino acids

Free amino acids (FAAs) constitute the largest component (∼40 %) of the so-called natural moisturizing factors of the skin. Their level declines in dry skin conditions and one strategy to overcome this problem may involve the topical delivery of FAAs through appropriate strategy. The objective of the present study was therefore to identify alternative skin models and study the corneocyte-water partition coefficients (KCOR/W) and permeation coefficient (KP) of 18 FAAs. The KCOR/W was studied using standard protocols and the permeation studies were conducted using Franz diffusion cell. The results indicate that the FAAs have high partitioning behavior to the corneocytes. The KCOR/W values of the human COR and that of pig ear skin were better correlated with each other than that of keratin isolated from chicken feathers. The presence of lipid in the stratum corneum (SC), initial concentration of the FAAs, and permeation enhancers affect the KCOR/W. The FAAs have low permeation into the SC which suggests the need for permeation enhancers in designing dosage form containing these compounds. Even though the investigated mathematical models show good prediction of the Kp values, better prediction could be obtained by considering factors such as the possible entrapment of the FAAs by the CORs.

Edukasi Dan Skrining Gula Darah Dan Anemia Dalam Rangka Mencegah Terjadinya Kulit Kering Pada Kelompok Lanjut Usia

Xerosis or dry skin occurs when the skin loses moisture, causing itching, cracking and dullness. This condition is common in the elderly due to physiological changes such as decreased activity of the sebaceous and sweat glands, as well as impaired skin barrier function. Anemia and uncontrolled blood sugar levels can worsen dry skin conditions in the elderly. Therefore, this community service activity was carried out with the aim of increasing awareness of the elderly about the importance of maintaining healthy skin related to anemia and blood sugar. This activity includes education about preventing and managing dry skin, controlling blood sugar, and treating anemia. This activity uses the PDCA method to ensure that the activity process runs systematically and can be evaluated. The results of the activity showed that the majority of participants experienced mild anemia and a small number had abnormal blood sugar. This shows that intervention and health education are needed for the elderly group to improve their quality of life by maintaining hydration of their skin.

Going Beyond Ceramides in Moisturizers: The Role of Natural Moisturizing Factors.

Xerosis is experienced by almost everyone at some time in their lives and the foundation of management of dry skin (both consumer- and healthcare professional--directed) rests on the use of moisturizers. Given the wide range of available moisturizers, counseling patients about selecting the optimum moisturizer for their individual situation relies on knowledge of ingredients and formulations. Traditionally, the main focus for many moisturizers centered on the core functional and structural role of ceramides within the epidermal barrier.  However, while a key aspect of transepidermal water loss and other skin barrier functions, components other than ceramides are equally essential in increasing moisturization. The skin's natural moisturizing factors (NMFs) are a complex mixture of water-attracting compounds such as amino acids, urea, lactate, pyrrolidone carboxylic acid (PCA), and electrolytes which play a fundamental role in preserving physiologic function by regulating the water content of the stratum corneum. By facilitating water retention, NMFs contribute significantly to the suppleness, elasticity, normal desquamation, and overall integrity of the skin barrier. Incorporation of NMFs into moisturizers addresses critical deficiencies in the skin's moisture balance that exist in xerotic and atopic skin, and in many skin disorders, mitigating signs and symptoms associated with xerosis and promoting optimal skin health. The biochemical composition of NMFs and the intricate interplay with epidermal homeostasis translate to a central role in moisturizers used for prophylactic and therapeutic management of various dry skin conditions, beyond ceramides alone. J Drugs Dermatol. 2024;23(6):466-471.     doi:10.36849/JDD.8358.

Kegiatan Penapisan Kadar Air Dan Minyak Kulit Pada Populasi Dewasa Di SMP Kalam Kudus Jakarta

The skin, as the body's largest organ, can function as an important barrier against dangers from outside the body. Insufficient water and oil levels in the skin can cause dry skin conditions. This can be caused by various factors, including age, sun exposure, and accompanying chronic diseases. Dry skin tends to cause itching, thereby increasing the risk of scratching and injury. A good level of skin hydration will improve an individual's quality of life. This screening activity for the adult population at Kalam Kudus Middle School was attended by 127 participants with an average age of 39 years. The mean water and oil content in the left hand were 39.3% and 17.6%, respectively. Meanwhile, the average water and oil content in the right hand was 41.2% and 18.5%, respectively. Through this activity, participants are expected to increase awareness of the importance of maintaining body and skin moisture.

Influence of cosmetic foundation cream on skin condition during treadmill exercise.

There is a growing trend of individuals wearing cosmetics while participating in physical activities. Nonetheless, there remains a need for further understanding regarding the effects of makeup on the facial epidermis during exercise, given the existing knowledge gaps. This study aimed to evaluate the effects of a cosmetic foundation cream on skin conditions during physical activity. Forty-three healthy college students, 20 males (26.3 ± 1.5 years) and 23 females (23.1 ± 1.0 years), were enrolled in this study. Foundation cream was applied to participants on half of the face in two different areas (MT: makeup T zone and MU: makeup U zone). The other half of the face served as internal control (T: non-makeup T zone and U: non-makeup U zones). Skin levels of moisture, elasticity, pore, sebum, and oil were measured using a skin analysis device (Aramhuvis, Gyeonggi, Republic of Korea) before and after a 20-min treadmill exercise. Paired t-test and independent t-test were performed for skin condition measurements at pre- and postexercise. The skin moisture levels in both the T and MT significantly increased after exercise (p < 0.05) (pre-T: 24.5 ± 1.3, post-T: 38.5 ± 3.5 and pre-MT: 18.7 ± 0.7, post-MT: 40.4 ± 4.8). Elasticity also significantly improved in both the T and MT (p < 0.05) (pre-T: 25.6 ± 1.3, post-T: 41.5 ± 3.5 and pre-MT: 20.0 ± 0.9, post-MT: 41.7 ± 3.7). The size of the pores in the T zone observed a significant increase after exercise (p < 0.05) (pre-T: 41.7 ± 2.1, post-T: 47.8 ± 2.4). The sebum levels in the T zone exhibited a reduction following physical activity, whereas there was a notable increase in sebum levels in the makeup zones (p < 0.05) (pre-MT: 2.4 ± 0.7, post-MT:4.2 ± 0.8 and pre MU 1.8 ± 0.34, post MU 4.9 ± 0.9). The oil level was increased in the non-makeup zones (pre-T: 6.1 ± 1.4, post-T: 11.8 ± 2.0 and pre-U: 7.3 ± 1.5, post-U: 11.9 ± 1.9; p < 0.05) and decreased in the makeup zones (pre-MT: 13.3 ± 1.9, post-MT: 7.4 ± 2.3 and pre-MU: 22.1 ± 2.4, post-MU: 3.2 ± 1.0; p < 0.05). The findings suggest that using foundation cream during aerobic exercise can reduce skin oil, causing dryness. Additionally, makeup can clog pores and increase sebum production. Therefore, wearing makeup may not be recommended for people with dry skin conditions based on the results of the current study. This research offers important insights to the public, encouraging them to consider the possible consequences of using makeup while exercising.

Knowledge Level of Dry Skin Care in The Elderly at The Koto Tangah Regional Health Center

Introduction. The occurrence of dry skin in the elderly requires good and extra skin care. The incidence and severity of dry skin increases with age. Dry skin conditions in the elderly can cause discomfort and can even cause disease, such as atopic dermatitis which is a disease caused by inflammation of the skin. This research aims to determine the level of knowledge of dry skin care in the elderly at the Koto Tangah Health Center in the city of Padang. Methods. This research was a descriptive observational study with a cross-sectional design. The sample in this study was selected by technique consecutive sampling and this research requires a minimum of 100 samples. Results. The knowledge level of dry skin care of the respondents is mostly in the medium category (62%), the age of the majority of respondents was in the age category of 60-70 years (65%), the sex of the majority of respondents was male (53%), most respondents had primary school education (56%), worked as laborer (26%), and live with their families (83%). Conclusion. The level of knowledge of nursing for most of the elderly dry skin is in the medium category.

Cetyl alcohol, stearyl alcohol and colloidal oatmeal-based gentle skin cleanser in management of dry and sensitive skin: a cross-sectional study

Background: Effective skin cleansing is vital for maintaining skin health and appearance. An ideal skin cleaner retains moisture, removes oils, sweat, and dirt without causing irritation or dehydration. This study was designed to evaluate the efficacy, safety, tolerability and usage trends of a gentle skin cleanser containing cetyl alcohol, stearyl alcohol and colloidal oatmeal for individuals having dry and sensitive skin. Methods: We conducted a retrospective review at 102 centres, focusing on individuals aged 18 to 65 years with atopic dermatitis and dry skin conditions who required the use of gentle skin cleanser. Total 568 cases were taken; 488 cases of dry and sensitive skin were further analysed over a 2-week study period. Results: Gentle skin cleanser exhibited significant reduction (p&lt;0.0001) in skin dryness, itchiness and irritation by 4.42±1.92 (63.38%), 4.03±2.71 (49.38%) and 4.44±2.07 (65.58%) respectively in participants with dry skin and by 4.25±1.48 (58.49%), 3.26±3.22 (18.02%) and 4.42±1.56 (63.23%) in participants with sensitive skin after its regular usage. Participants provided positive feedback and expressed overall satisfaction with the study product. Conclusions: Skin cleanser was efficacious and well-tolerable in participants in providing moisturizing, soothing, exfoliating, and antioxidant effects making it a preferred primary choice for managing dry and sensitive skin. The cleanser effectively cleansed excess oil, dirt, dead cells, microorganisms, and sweat providing a gentle and mild experience, in daily skin care.

Aloe vera, wheat germ oil, tea tree extract and honey-based emollient cream in the management of atopic dermatitis: a post-hoc analysis

Background: Atopic dermatitis is a chronic skin condition characterized by dry, itchy and inflamed skin. This study evaluated the complementary benefits efficacy and tolerability of emollient c containing Aloe vera, Wheat germ oil, tea tree extract, and honey in patients with dry skin conditions. Methods: Cross-sectional analysis for clinical cases with dry skin receiving moisturizing cream formulation was undertaken at 156 centres. 286 case records of atopic dermatitis receiving standard of care as cleansers, Topical corticosteroids, moisturizers were further analysed for improvement in skin dryness and itchiness. Results: Regular use of Emollient formulation containing aloe vera, wheat germ oil, tea tree extract, honey was further analysed along with safety assessment over 8 weeks of observation period. The mean age of the study participants was 36.58 years. There was significant change in VAS score for dryness (p-value&lt; 0.01), itch (p-value &lt;0.01) with Patient Global Assessed rating as good (64.23%) for effectiveness and ease of application. Mild stinging, mild burning and irritation was experienced by 5 (1.75%) patients. Conclusions: The aloe vera, wheat germ oil, tea tree extract, honey enriched emollient formulation was efficacious and well tolerable in study participants in providing moisturizing, antimicrobial, and anti-inflammatory effects making it a preferred complementary therapy for managing atopic dermatitis following the short course therapy with TCS as a pertinent clinical strategy to avoid the atopic flares in such cases.

Delivery of free amino acids into and through the stratum corneum of the skin using micro emulsions and microemulsion-based hydrogels: Formulation, characterization, and ex-vivo permeation studies.

Free amino acids constitute the largest portion (40%) of the natural moisturizing factor. Their level might decline and cause dry skin condition. The treatment strategy involves the replenishment of these components to the skin, and, to our knowledge, there are no reports that involve dermal delivery of free amino acids. The purpose of the current study was therefore to prepare and characterize different micro-emulsions, micro-emulsion-based hydrogels, and hydrophilic creams loaded with free amino acids for dermal delivery. Oil-in-water microemulsions were prepared using carefully selected formulation components. Poloxamer® 407 and carbopol® 934 were used to prepare the hydrogels. All the formulations were characterized for physico-chemical, permeation and cytotoxicity properties. The results showed that the prepared microemulsions had desired droplet size, size distribution, zeta potential, refractive index, and pH. In the gel preparations, the elastic properties prevailed over the viscous behavior. The hydrogels had non-Newtonian shear-thinning behavior with some thixotropic properties. The free amino acids permeated into the deeper layers of the stratum corneum from the microemulsions, and microemulsion-based hydrogels as compared to conventional hydrophilic cream. The hydrogels were more effective than the microemulsions to deliver the FAAs to the desired site of the skin in a sustained manner. Poloxamer-based hydrogel permeated into deeper skin layers than Carbopol-based hydrogel. Formulations prepared using standard free amino acids and those extracted and purified from oyster mushroom had similar characteristics. All the formulations were stable and safe to be applied topically. In conclusion, microemulsions and microemulsion-based hydrogels can be considered as safe carrier systems for dermal delivery of free amino acids.

Mind and skin: Exploring the links between inflammation, sleep disturbance and neurocognitive function in patients with atopic dermatitis.

Atopic dermatitis (AD) is a chronic, pruritic and inflammatory, dry skin condition with many known comorbidities. These include airway disease, food allergies, atopic eye disease and autoimmune conditions. Furthermore, there is often significant sleep disturbance as well as increased psychological distress and mental health problems. Severe AD therefore often has a significant impact on the quality of life of both patients and their families. In this review we discuss recent findings on the putative links between AD, its association with itch, sleep disturbance and neuropsychiatric morbidity, including the role of inflammation in these conditions. Itch was thought to predominantly drive sleep disruption in AD. We now understand changes in sleep influence immune cell distribution and the associated inflammatory cytokines, which suggests a bidirectional relationship between AD and sleep. We also increasingly recognize inflammation as a key driver in psychological symptoms and disorders. The link between cutaneous, systemic and possible brain inflammation could at least in part be driven by the sleep deprivation and itch-driven neuronal proliferation seen in AD.

Changes in the AGE/Macrophage/TNF-α Pathway Affect Skin Dryness during KK-Ay/Tajcl Mice Aging.

Skin dryness associated with type 2 diabetes worsens with age; however, the underlying mechanisms remain unclear. Herein, we investigated the effects of aging on skin dryness using a type 2 diabetes mice model. Specific pathogen-free KK-Ay/TaJcl mice of different ages (10, 27, 40, and 50 weeks) were used in this study. The results confirmed that skin dryness worsens with age. Furthermore, increased levels of advanced glycation end products (AGE), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF)-α, along with an increased expression of the major AGE receptor (RAGE), an increased macrophage number, and decreased collagen expression were observed in the skin of aged KK-Ay/TaJcl mice. In conclusion, dry skin conditions worsen with age in diabetic mice, and the AGE/RAGE/PGE2 and TNF-α pathways play an important role in exacerbating skin dryness during aging in these mice.

Teat open lesions can lead to challenges at milking time on dairies in the Northeast United States.

During evaluations of teat skin by the authors using National Mastitis Council procedures, teat open lesions (TOL) have been more commonly identified in dairies in the Northeast United States over the last 10 years. The TOL described here are found in all stages of lactation and in any age lactating cow, which is unique from TOL that present mainly in first lactation animals just after calving. Cows with these TOL exhibit more abnormal cow behaviors during the milking event. Based on the authors' subjective field evaluations, dry teat skin condition appears to be a significant risk factor. Although there is a paucity of published literature, the other risk factors that the authors have observed are exposure to wind and significant temperature fluctuations, wet bedding, certain bedding additives, and occasionally mechanical, chemical, or thermal trauma. Teat open lesions have been observed in herds with all the common types of bedding. Treatment and preventative measures have focused on supporting skin conditions through higher emollients in the postmilking teat disinfection (PMTD) and controlling the environmental conditions to which the teat is exposed. This includes an evaluation of cow positioning in the stall as well as bedding levels, which influence bedding contamination. The accuracy of PMTD application can also have an influence. The objective of this narrative review was to search the current literature describing TOL, identify knowledge gaps, describe the authors' field experience with TOL on dairy operations in the Northeast United States, and identify opportunities for future research.

Moisturizing at a molecular level - The basis of Corneocare.

This review covers the last 20 years of research we and our collaborators have conducted on ethnic differences in facial skin moisturization placed in historical context with previous research. We have focussed particularly on the biochemical and cellular gradients of the stratum corneum (SC) with the aim of discovering new skin moisturization and SC maturation mechanisms, identifying new technologies and/or providing conceptual innovations for ingredients that will improve our understanding and treatment of dry skin. Specifically, we discuss gradients for corneodesmosomes and proteases, corneocyte phenotype-inducing enzymes, filaggrin and natural moisturizing factor (NMF), and barrier lipids. These gradients are interdependent and influence greatly corneocyte maturation. The interrelationship between corneodesmolysis and the covalent attachment of ω-hydroxy ceramides and ω-hydroxy fatty acids to the corneocyte protein envelope forming the corneocyte lipid envelope is especially relevant in our new understanding of mechanisms leading to dry skin. This process is initiated by a linoleoyl-ω-acyl ceramide transforming enzyme cascade including 12R lipoxygenase (12R-LOX), epidermal lipoxygenase-3 (eLOX3), epoxide hydrolase 3 (EPHX3), short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7), ceramidase and transglutaminase 1. Our research has opened the opportunity of using novel treatment systems for dry skin based on lipids, humectants, niacinamide and inhibitors of the plasminogen system. It is clear that skin moisturization is a more complex mechanism than simple skin hydration.

Development of an in vitro Functional Assay to Evaluate the Occlusive Properties of Moisturizers on Dry Skin

Introduction: Dry skin is a hallmark of impaired skin barrier function. Moisturizers are a mainstay of treatment to help the skin retain moisture, and there is a high consumer demand for effective products. However, the development and optimization of new formulations are hampered due to lack of reliable efficacy measures using in vitro models. Methods: In this study, a microscopy-based barrier functional assay was developed using an in vitro skin model of chemically induced barrier damage to evaluate the occlusive activity of moisturizers. Results: The assay was validated by demonstrating the different effects on barrier function between humectant (glycerol) and occlusive (petrolatum). Significant changes in barrier function were observed upon tissue disruption, which was ameliorated by commercial moisturizing products. Conclusion: This newly developed experimental method may be helpful to develop new and improved occlusive moisturizers for the treatment of dry skin conditions.

Rg3-enriched Korean red ginseng alleviates chloroquine-induced itch and dry skin pruritus in an MrgprA3-dependent manner in mice

BackgroundPrevious studies have found that Korean red ginseng extract (KRG) has antipruritic effects, which can be attributed to the presence of Rg3, one of the most potent ginsenosides. Therefore, Rg3-enriched KRG extract (Rg3EKRG) is anticipated to have enhanced antipruritic effects. The present study was conducted to examine the effects of Rg3EKRG in acute chloroquine (CQ)-induced and chronic dry skin pruritus. MethodsCalcium imaging technique was used in HE293T cells expressing MrgprA3 and TRPA1 (“MrgprA3/TRPA1”) and in primary cultures of mouse dorsal root ganglia (DRG) neurons. Mouse scratching behavior tests were performed on dry skin models. To verify the altered expression of itch-related genes, real-time RNA sequencing analysis and PCR were performed on DRG sections obtained from dry skin models. ResultsRg3EKRG suppressed CQ-induced intracellular calcium changes to a greater degree than KRG. Rg3EKRG dose-dependently inhibited CQ-induced responses in MrgprA3/TRPA1 cells. Rg3EKRG likely targeted MrgprA3 rather than TRPA1 to exert its inhibitory effect. Further, Rg3EKRG strongly inhibited the scratching behavior in mice induced by acute CQ injection. Importantly, DRG neurons obtained from dry skin mice models showed increased mRNA levels of MrgprA3, and treatment with Rg3EKRG alleviated chronic dry skin conditions and suppressed spontaneous scratching behaviors. ConclusionThe results of the present study imply that Rg3EKRG has a stronger antipruritic effect than KRG, inhibiting both acute CQ-induced and chronic dry skin pruritus in an MrgprA3-dependent manner. Therefore, Rg3EKRG is a potential antipruritic agent that can suppress acute and chronic itching at the peripheral sensory neuronal level.

Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice.

Although neuronal Toll-like receptors (TLRs) (e.g.,TLR2, TLR3, and TLR7) have been implicated in itch sensation, the roles of keratinocyte TLRs in chronic itch are elusive. Herein, we evaluated the roles of keratinocyte TLR2 and TLR7 in chronic itch under dry skin and psoriasis conditions, which was induced by either acetone-ether-water treatment or 5% imiquimod cream in mice, respectively. We found that TLR2 and TLR7 signaling were significantly upregulated in dry skin and psoriatic skin in mice. Chronic itch and epidermal hyperplasia induced by dry skin or psoriasis were comparably reduced in TLR2 and TLR7 knockout mice. In the dry skin model, the enhanced messenger RNA(mRNA) expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, TNF-α, and IFN-γ were inhibited in TLR2-/- mice, while CXCL2, IL-31, and IL-6 were inhibited in TLR7-/- mice. In psoriasis model, the enhanced mRNA expression levels of pruritic CXCL1/2, IL-31, IL-33, ST2, IL-6, and TNF-α were inhibited in TLR2-/- mice, while CXCL1/2, IL-31, IL-33, ST2, IL-6, IL-17A, and TNF-α were inhibited in TLR7-/- mice. Incubation with Staphylococcus aureus (S. aureus) peptidoglycan (PGN-SA) (a TLR2 agonist), imiquimod (a TLR7 agonist), and miR142-3p (a putative TLR7 agonist) were sufficient to upregulate the expression of pruritic cytokines or chemokines in cultured keratinocyte HaCaT cells. Finally, pharmacological blockade of C-X-C Motif Chemokine Receptor 1/2 and high mobility group box protein 1 dose-dependently attenuated acute and chronic itch in mice. Together, these results indicate that keratinocyte TLR2 and TLR7 signaling pathways are distinctly involved in the pathogenesis of chronic itch.