To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Atopic dermatitis (AD) is a chronic inflammatory skin condition. Natural products have gained traction in AD treatment due to their accessibility, low toxicity, and favorable pharmacological properties. However, their application is primarily constrained by poor solubility, instability, and limited permeability. The transdermal drug delivery system (TDDS) offers potential solutions for transdermal delivery, enhanced penetration, improved efficacy, and reduced toxicity of natural drugs, aligning with the requirements of modern AD treatment. This review examines the application of hydrogels, microneedles (MNs), liposomes, nanoemulsions, and other TDDS-carrying natural products in AD treatment, with a primary focus on their effects on penetration and accumulation in the skin. The aim is to provide valuable insights into the treatment of AD and other dermatological conditions.
Animals ; Humans ; Administration, Cutaneous ; Biological Products/pharmacokinetics* ; Dermatitis, Atopic/drug therapy* ; Drug Delivery Systems ; Hydrogels/chemistry* ; Skin/metabolism* ; Skin Absorption

BACKGROUNDTetracycline (TET) has been found to have both antibiotic and anti-inflammatory properties. The anti-inflammatory effect of topical TET on atopic dermatitis (AD) has not been reported. The purpose of this study was to explore the potential role of topical TET and its anti-inflammatory effects in a mouse model of AD.

METHODSThe 2% TET was applied topically to ears of MC903-induced AD-like BALB/c mice once a day. AD-like symptoms and severity were evaluated by assessing skin scoring of dermatitis, ear thickness, and frequency of scratching. Serum IgE and thymic stromal lymphopoietin (TSLP) levels were measured by enzyme-linked immunosorbent assay. Western blot was used for analyzing the expressions of TSLP, protease-activated receptor 2 (PAR2), and nuclear factor-kappa B (NF-κB) in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of TSLP and inflammatory cytokines including interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-α, and IL-1β in skin lesions.

RESULTSScoring of dermatitis (9.00 ± 0.63 vs. 6.67 ± 1.03, P = 0.001), ear thickness (0.44 ± 0.02 mm vs. 0.40 ± 0.03 mm, P = 0.018), and serum IgE level (421.06 ± 212.13 pg/ml vs. 244.15 ± 121.39 pg/ml, P = 0.047) were all improved in the 2% TET treatment group compared with AD group. Topical TET significantly reduced the serum level of TSLP (119.04 ± 38.92 pg/ml vs. 65.95 ± 54.61 pg/ml, P = 0.011) and both mRNA and protein expressions of TSLP in skin lesions compared with AD group (P = 0.003 and 0.011, respectively), and NF-κB and PAR2 expression in skin lesions were also suppressed (P = 0.016 and 0.040, respectively). Furthermore, expressions of inflammatory cytokines IL-4, IL-13, and TNF-α in skin lesions were down-regulated in 2% TET group compared with AD group (P = 0.035, 0.008, and 0.044, respectively).

CONCLUSIONSTopical TET exerted anti-inflammatory effects through suppression of TSLP and inflammatory cytokines in AD mouse model, suggesting TET as a potential agent for the topical treatment of AD in the future.

Administration, Topical ; Animals ; Calcitriol ; analogs & derivatives ; toxicity ; Cytokines ; Dermatitis, Atopic ; chemically induced ; drug therapy ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Female ; Interleukin-13 ; metabolism ; Interleukin-4 ; metabolism ; Mice ; Mice, Inbred BALB C ; Tetracyclines ; administration & dosage ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism

PURPOSE: The purpose of this study was to evaluate the effects of essential oil on oxidative stress, immunity, and skin condition in atopic dermatitis (AD) induced mice. METHODS: This study was a 3x3 factorial design. Factors were oil type (Lavender, Thyme, and 2:1 mixture of lavender and thyme oil [blending oil]) and treatment period (0 day, 7 days, and 21 days). The samples were 45 mice with AD and randomly assigned to nine groups of five mice per group. The dependent variables such as superoxide radical, IgE, degranulated mast cells, and epidermal thickness were measured. Data were collected from February to April in 2014. Descriptive statistics, One-way ANOVA, Two-way ANOVA, and Tukey's HSD test were performed using the SPSS WIN 20.0 program. RESULTS: Dependent variables were not statistically significantly different by the three oil types (p >.05). Essential oils such as lavender, thyme, and blending oil were all effective in reducing AD symptoms and especially 2:1 blending oil were most effective. There were statistically significant differences by the three treatment periods in all dependent variables (p <.001). There were statistically significant interactions between oil types and treatment periods in all dependent variables (p <.01). For decreasing superoxide radical, degranulated mast cells, and epidermal thickness, 2:1 mixed oil should be applied for at least 21 days. Otherwise to reduce IgE, 2:1 mixed oil should be used for at least 7 days. CONCLUSION: These findings provide bases for developing effective interventions for AD patients to manage their AD symptoms.
Animals ; Dermatitis, Atopic/chemically induced/*drug therapy/pathology ; Disease Models, Animal ; *Immunity/drug effects ; Immunoglobulin E/blood ; Lavandula/*chemistry/metabolism ; Mast Cells/cytology/metabolism ; Mice ; Oils, Volatile/chemistry/pharmacology/therapeutic use ; *Oxidative Stress/drug effects ; Picryl Chloride/toxicity ; Plant Oils/chemistry/pharmacology/*therapeutic use ; Singlet Oxygen/metabolism ; Skin/drug effects/pathology ; Thymus Plant/*chemistry/metabolism

OBJECTIVETo investigate the effectiveness of pimecrolimus cream 1% for sensitive skin in adult women and its underlying mechanisms.

METHODSThe changes of subjective symptoms and signs were evaluated before and after the application of pimecrolimus cream 1% based on the severity of pruritus (SP) and severity of burning sensation (SB) scores, and on a basic syntax and molecular substrate (molecular psychophysics) of nociception and proprioception established by temperature-sensitive transient receptor potential (TRP) channels.

RESULTSThe SP and SB scores were significantly decreased in 32 patients with sensitive skin after using topical pimecrolimus cream 1% (P<0.05). Twenty (62.5%) patients showed positive capsaicin-like response (i.e. burning with consequent rapid amelioration of pruritus or burning sensation) and 6 (18.8%) showed positive camphor-like response (i.e. warming with consequent rapid amelioration of pruritus) on application sites after using the topical pimecrolimus cream 1%, and 6 (18.8%) showed negative capsaicin-like response and/or negative camphor-like response.

CONCLUSIONSPimecrolimus may rapidly inhibit or alleviate itch or burning sensation of patients with sensitive skin. The therapeutic effect of pimecrolimus is relevant to the mechanisms that activate or sensitize transient receptor potential vanilloid 1 (TRPV1) and desensitizes TRPV1 in the skin sensory afferents.

Adolescent ; Adult ; Dermatitis, Atopic ; drug therapy ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Pruritus ; drug therapy ; Skin ; drug effects ; TRPV Cation Channels ; metabolism ; Tacrolimus ; analogs & derivatives ; therapeutic use ; Young Adult

The safety of accelerated schedules of allergen immunotherapy (ASAI) in patients with bronchial asthma (BA) has been reported but there are little data on the safety of ASAI for patients with atopic dermatitis (AD). In this study, we investigated the safety of ASAI in patients with AD. Sixty patients with AD and 18 patients with BA sensitized to house dust mites (HDM) were studied. A maximum maintenance dose of HDM extract, adsorbed to aluminum hydroxide, was administered to patients by subcutaneous injection with either a 3-day protocol (rush immunotherapy) or 1-day protocol (ultra-rush immunotherapy). Systemic reactions were observed 4 of 15 patients (26.7%) with AD during rush immunotherapy, 13 of 45 patients (28.9%) with AD during ultra-rush immunotherapy, and 4 of 18 patients (22.2%) with BA during rush immunotherapy (P > 0.05). No severe or near fatal systemic reactions occurred in 78 subjects of this study. Systemic reactions developed within 4 hr after administration of the maximum allergen dose in 20 of 21 patients (95.2%) with AD and BA who showed systemic reactions during rush or ultra-rush immunotherapy. In conclusion, ASAI was safe and well tolerated in patients with AD. ASAI can be a useful therapeutic option for AD.
Adolescent ; Adult ; Allergens/*therapeutic use ; Aluminum Hydroxide/chemistry ; Animals ; Asthma/therapy ; Dermatitis, Atopic/immunology/*therapy ; Desensitization, Immunologic/*methods ; Drug Administration Schedule ; Female ; Humans ; Infusions, Subcutaneous ; Male ; Pyroglyphidae/*immunology/metabolism

Increased transepidermal water loss (TEWL) and downregulated antimicrobial peptides (AMPs) are observed in patients with atopic dermatitis (AD). Tacrolimus and ceramide-dominant emollients are effective in the treatment of AD by preventing the production of inflammatory cytokines and by correcting skin barrier dysfunctions, respectively. Present study was designed to investigate the relationship between antimicrobial and barrier factors by measuring the changes of AMPs and TEWL after topical application of tacrolimus and ceramide-dominant emollient in the patients with AD. A total of three patients with AD were treated with tacrolimus in one lesion and ceramide-dominant emollient in another lesion for 4 weeks. RT-PCR and western blotting revealed that the mRNA and protein expression levels of hBD-2 and LL-37 were increased on the both study sites. Immunohistochemical analysis showed significant increase of AMPs and IL-1alpha, while, IL-4 was decreased on the both study sites. The mean changes of TEWL and AMPs showed no statistical difference between both sites. Tacrolimus and ceramide-dominant emollient influence on both TEWL and AMPs expression in patients with AD, namely they have similar effects on both of the two. This study shows that restoration of permeability barrier function is accompanied by the concomitant improvement of antimicrobial defense in patients with AD.
Administration, Topical ; Adolescent ; Antimicrobial Cationic Peptides/*metabolism ; Ceramides/*administration & dosage ; Dermatitis, Atopic/*drug therapy/*metabolism ; Emollients/administration & dosage ; Female ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Skin Absorption/*drug effects ; Tacrolimus/*administration & dosage ; Treatment Outcome ; Water Loss, Insensible/*drug effects ; Young Adult