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Objective To reveal the mechanism of Mahuang Lianqiao Chixiaodou decoction and its disassembled formula for improving the skin barrier function in a mouse model of atopic dermatitis (AD). Methods Sixty specific-pathogen free male BALB/c mice were randomly divided into the control group, model group, whole formula group (WF), exterior-releasing formula group (ERF), interior-clearing formula group (ICF), and positive control group (PC). A mouse model of AD was established using the semi-antigen 2,4-dinitrofluorobenzene induction method. The lesion scores, transepidermal water loss and pH, and skin histopathology of mice in each group were observed. The expressions of filaggrin, loricrin, and involucrin were detected by the streptavidin peroxidase immunohistochemical method and western blotting, and their mRNA expressions were detected by quantitative polymerase chain reaction. Results Mice in the WF, ERF, ICF, and PC groups showed reduced skin lesion performance, improved histopathology, decreased skin lesion score, transepidermal water loss and pH, and upregulated expressions of proteins including filaggrin, loricrin, and involucrin, and their mRNAs. The most obvious regulatory effect was observed in the WF group, followed by the ICF, ERF, and PC groups, accordingly. Conclusions Mahuang Lianqiao Chixiaodou decoction and its disassembled formula can improve the skin barrier function in a mouse model of AD by upregulating filaggrin, loricrin, and involucrin, and their mRNA expressions, and the most optimal effect was noted in the WF group, followed by the ICF and ERF groups, which suggests that the effect of clearing heat and resolving dampness in improving the skin barrier function of AD is more obvious and is one of the key treatments for AD.

Individualized homeopathy (IH) in atopic dermatitis (AD) remained under-researched.We aimed at evaluating efficacy of IH in AD.A double-blind, randomized, placebo-controlled, short-term, preliminary trial was conducted in an Indian homeopathy hospital. Patients were randomized to either IH (n = 30) or identical-looking placebo (n = 30) using computerized randomization and allocation. Outcomes were patient-oriented scoring of AD (PO-SCORAD; primary end point), Dermatological Life Quality Index (DLQI) score, and AD burden score for adults (ADBSA; secondary end points), measured monthly for 3 months. An intention-to-treat sample was analyzed after adjusting baseline differences.On PO-SCORAD, improvement was higher in IH against placebo, but nonsignificant statistically (pmonth 1 = 0.433, pmonth 2 = 0.442, pmonth 3 = 0.229). Secondary outcomes were also nonsignificant - both DLQI and ADBSA (p0.05). Four adverse events (diarrhea, injury, common cold) were recorded.There was a small, but nonsignificant direction of effect towards homeopathy, which renders the trial inconclusive. A properly powered robust trial is indicated.Einleitung: Die Anwendung der individualisierten Homöopathie (IH) bei atopischer Dermatitis (AD) ist bislang wenig erforscht. Ziel: Mit der vorliegenden Studie sollte die Wirksamkeit der IH bei AD untersucht werden. Methoden: Es handelt sich um eine erste doppelblinde, randomisierte, plazebokontrollierte Kurzzeitstudie, die in einer indischen Klinik für Homöopathie durchgeführt wurde. Die Patienten wurden mittels computergestützter Randomisierung und Zuordnung einer Behandlung mit IH (n = 30) oder einem identisch aussehenden Plazebo (n = 30) zugewiesen. Endpunkte waren die monatlich über 3 Monate gemessene patientenorientierte Beurteilung der AD (patient-oriented scoring of AD, PO-SCORAD; primärer Endpunkt), der Score des Dermatological Life Quality Index (DLQI) und der AD-Belastungs-Score für Erwachsene (AD burden score for adults, ADBSA; sekundäre Endpunkte). Die Analyse der Intent-to-treat-Stichprobe erfolgte nach Korrektur für die Baseline-Unterschiede. Ergebnisse: Die Verbesserung des PO-SCORAD-Werts fiel in der IH-Gruppe höher aus als in der Plazebogruppe, allerdings erreichte der Unterschied keine statistische Signifikanz (pMonat 1 = 0,433, pMonat 2 = 0,442, pMonat 3 = 0,229). Die sekundären Endpunkte DLQI und ADBSA waren ebenfalls nicht signifikant (p0,05). Vier unerwünschte Ereignisse (Diarrhoe, Verletzung, Erkältung) wurden erfasst. Schlussfolgerungen: Die Studie zeigte eine leichte, jedoch nichtsignifikante Wirksamkeitstendenz zugunsten der Homöopathie, lieferte jedoch keine eindeutigen Hinweise. Die Durchführung einer robusten Studie mit ausreichender statistischer Power ist angezeigt.

The use of Cannabis sativa is currently recognized to ease certain types of chronic pain, reduce chemotherapy-induced nausea, and improve anxiety. Nevertheless, few studies highlighted the therapeutic potential of C. sativa extracts and related phytocannabinoids for a variety of widespread skin disorders including acne, atopic dermatitis, psoriasis, pruritus, and pain. This review summarized the current evidence on the effects of phytocannabinoids at the cutaneous level through the collection of in vitro, in vivo, and clinical studies published on PubMed, Scopus, Embase, and Web of Science until October 2020. Phytocannabinoids have demonstrated potential anti-inflammatory, antioxidant, anti-aging, and anti-acne properties by various mechanisms involving either CB1/2-dependent and independent pathways. Not only classical immune cells, but also several skin-specific actors, such as keratinocytes, fibroblasts, melanocytes, and sebocytes, may represent a target for phytocannabinoids. Cannabidiol, the most investigated compound, revealed photoprotective, antioxidant, and anti-inflammatory mechanisms at the cutaneous level, while the possible impact on cell differentiation, especially in the case of psoriasis, would require further investigation. Animal models and pilot clinical studies supported the application of cannabidiol in inflammatory-based skin diseases. Also, one of the most promising applications of non-psychotropic phytocannabinoids is the treatment of seborrheic disorders, especially acne. In conclusion, the incomplete knowledge of the role of the endocannabinoid system in skin disorders emerged as an important limit for pharmacological investigations. Moreover, the limited studies conducted on C. sativa extracts suggested a higher potency than single phytocannabinoids, thus stimulating new research on phytocannabinoid interaction.

Background Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease that affects 1–3% of adults worldwide. Currently, it is not possible to completely cure AD; therefore, alternative treatments need to be developed to meet the patients’ needs. Here, based on our previous pilot study, we conducted the first confirmatory randomized controlled trial to evaluate the effect of acupuncture in patients with mild to moderate AD. Methods A randomized, participant- and assessor-blinded, sham-controlled trial was designed with an intervention period twice-weekly for 4 weeks and a 4-week follow-up. We equally allocated 36 participants to the verum acupuncture (VA) and sham acupuncture (SA) groups. The main outcome measure was the change in SCORing Atopic Dermatitis index (SCORAD) score before and after treatment. Results A total of 36 participants, aged 19 to 38 years, were enrolled, and 35 were included in the intention-to-treat analyses. The mean change in total SCORAD score differed significantly among the two groups at 4 weeks after randomization (P P Conclusions Twice-weekly acupuncture treatment was effective in reducing AD symptoms in patients with mild to moderate AD without serious adverse events. Trial registration Clinical Research Information Service Identifier: KCT0002796.

Cannabinoids (CBDs) represent a diverse class of chemicals that may be beneficial in the treatment of various skin diseases due to antipruritic, anti-inflammatory, and antinociceptive properties. Although the legal history of these compounds has previously restricted their use and study, it seems likely that CBDs will gain popularity as they become increasingly available. We examined the mechanisms in which CBDs may have potential in the field of dermatology and reviewed the existing literature. We suggest that dermatologists review the existing evidence for CBD use and be ready to discuss it with their patients. The current literature indicates that CBDs may be beneficial in skin disease, particularly in the treatment of acne, chronic pruritus, and atopic dermatitis. Although there is preliminary evidence to suggest that CBDs are beneficial in these conditions, existing studies tend to be small and lacking rigorous design. There is a clear need for high-quality randomized controlled trials to fully evaluate the efficacy and safety of these compounds before their use can be promoted in the treatment of dermatological diseases.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied with itchy and scaly rash. Compound traditional Chinese medicine dermatitis ointment (CTCMDO) consists of a mixture of extracts from five plants, which had been used in AD treatment due to good anti-inflammatory and anti-allergic effects. Materials and methods In this study, high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometer (LC/MS) were performed to analyze the active ingredients of CTCMDO in detail and to establish its HPLC fingerprint. Furthermore, the anti-inflammatory and antipruritic activities of CTCMDO were studied in the treatment of DNCB-induced AD in mice. Results A total of 44 compounds including phenylpropionic acid compounds, alkaloid compounds, curcumin compounds and lignans were identified via combined HPLC and LC/MS. A fingerprint with 17 common peaks was established. In AD-like mice, DNCB-induced scratching behavior had been suppressed in the treatment of CTCMDO in a dose-dependent manner. Furthermore, the detailed experimental results indicated that the AD can be effectively improved via inhibiting the production of Th1/2 cytokines in serum, reversing the upregulation of substance P levels of itch-related genes in the skin, and suppressing the phosphorylation of JNK, ERK, and p38 in the skin. Conclusion This work indicated that CTCMDO can significantly improve AD via attenuating the pathological alterations of Th1/2 cytokines and itch-related mediators, as well as inhibiting the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB).

Objectives: Atopic dermatitis (AD) is a prevalent and chronic, pruritic inflammatory skin condition that can influence all age groups. AD is associated with a poor health-related quality of life. This randomized clinical trial was performed to compare the effectiveness of Olivederma (combination of aloe vera and virgin olive oil) or betamethasone regarding disease severity, quality of life, serum IgE and eosinophil count. Methods: Thirty-six AD patients were randomly allocated to topical Olivederma or betamethasone, and were followed for 6 weeks. Results: Total SCORAD severity scores showed significant decrease in both groups, while it was more prominent in Olivederma group (64.5% improvement in Olivederma vs. 13.5% improvement in Betamethasone, p-value < 0.001). Quality of life (DLQI questionnaire) of AD patients was significantly improved after 6 weeks treatment with Betamethasone (22.3%, p < 0.001) and Olivederma (60.7%, p-value < 0.001). Olivederma group showed a significantly lower DLQI score in comparison with Betamethasone treated patients after 6 weeks of therapy (p < 0.001). Improvements in eosinophil count and serum IgE was observed. Conclusion: In summary, this study shows that Olivederma is superior to topical Betamethasone after 6 weeks of therapy with regard to disease severity, quality of life and eosinophil count.

Objectives. Herbal medicine (HM) is attracting attention for treating atopic dermatitis (AD). This overview was conducted to summarize and critically evaluate the current systematic reviews (SRs) on HM for the treatment of AD. Methods. Through comprehensive searches, all relevant SRs on HM for AD published until May 2020 were included. The quality of included SRs was assessed using the AMSTAR-2 tool. Moreover, original randomized controlled trials (RCTs) included in the SRs were resynthesized to investigate the efficacy and safety of oral HM for AD. The quality of evidence for the main findings was evaluated using the GRADE approach. Results. Nine SRs were included in this overview. HM showed significantly better efficacy in terms of total effective rate (TER), itching and sleep symptom scores, quality of life, and the dose of topical treatment used compared with placebo. HM as a monotherapy and/or an adjunctive therapy to conventional medication (CM) showed significantly better results on the efficacy, symptom relief, and some laboratory parameters related to the inflammatory response. The methodological quality was generally low. When 58 original RCTs were reanalyzed, HM showed significantly lower SCORing Atopic Dermatitis (SCORAD) score and higher TER than the placebo or CM. In terms of the safety profile, HM was not significantly different from the placebo and was better than CM. The quality of evidence ranged from “moderate” to “very low.” Conclusion. The results suggested that HM as a monotherapy or an adjunctive therapy is promising for the treatment of AD. However, due to low methodological quality and low quality of evidence, further rigorous, well-designed, high-quality SRs, and RCTs are needed to make clinical recommendations on HM use.

Background Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. p-coumaric acid (pCA) is an active ingredient of Panax ginseng Meyer (Araliaceae). Methods Here, we estimated an anti-AD effect of pCA on activated mast cells, activated splenocytes, and a mouse model of AD. Cytokines levels were measured by ELISA and protein activation was analyzed by Western blotting. 2,4-dinitrofluorobenzene (DNFB) was used to induce AD-like skin lesions. Results The treatment with pCA suppressed the productions and mRNA expressions of thymic stromal lymphopoietin (TSLP), TNF-ɑ, IL-6, and IL-1β in HMC-1 cells. pCA downregulated the expressions of RIP2 and caspase-1, phosphorylated-(p)p38/pJNK/pERK, and pIKKβ/pIkBɑ/NF-κB in HMC-1 cells. pCA also decreased the productions of TSLP, TNF-ɑ, IL-6, IL-4, and IFN-γ in the supernatant of stimulated splenic cells. Comparing to DNFB-sensitized control group, pCA-treated group alleviated pathological changes of AD-like lesions. pCA decreased the proteins and mRNA expressions levels of TSLP, IL-6, and IL-4 in the skin lesions. Caspase-1 activation was also downregulated by pCA treatment in the AD-like lesions. The serum levels of histamine, IgE, TSLP, TNF-ɑ, IL-6, and IL-4 were suppressed following treatment with pCA. Conclusion This study suggests that pCA has the potential to improve AD by suppressing TSLP as well as inflammatory cytokines via blocking of caspase-1/NF-κB signal cascade.

Atopic dermatitis (AD) is a chronic and relapsing inflammatory disease that affects 1%–20% of people worldwide. Despite affecting many people, AD current treatments, such as corticosteroids and calcineurin inhibitors, have not only harmful secondary effects but are also often ineffective. Therefore, natural nontoxic compounds are on high demand for developing new effective AD treatments. Panax ginseng Meyer has been used traditionally for its promising healing and restorative properties to treat many diseases including skin disorders, reason why in this review we want to explore the research performed with AD and P. ginseng as well as determining its potential for new drug development. Previous researches have shown that P. ginseng has positive effects in AD patients such as lower eczema area and severity index, transepidermal water loss, and immunoglobulin E levels and better quality of sleep. In vivo animal models, as well, have shown positive results to P. ginseng and derived ginsenosides, such as the decrease of transepidermal water loss, immunoglobulin E levels in serum, allergy-related cytokines, and downregulation of NF-κB, MAPK, and Ikaros pathways. All of these previous data suggest that P. ginseng and its derived ginsenosides are undoubtedly a nontoxic effective option to treat AD. Keywords: Alternative medicine, Atopic dermatitis, Filaggrin, Ginsenosides, Panax ginseng

Context The natural products derived from Capparis ecuadorica H.H. Iltis (Capparaceae) could have great potential for anti-inflammation since they inhibited the inflammatory response in lipopolysaccharide (LPS)‐stimulated RAW 264.7 cells. Object This study investigated the anti-inflammatory effects and related mechanism of methanol extract of C. ecuadorica leaves (MCE) during atopic dermatitis (AD) responses. Materials and methods Alterations in the phenotypical markers for AD, luciferase signal, iNOS‐mediated COX‐2 induction pathway, and inflammasome activation were analysed in non-Tg (n = 5) and 15% phthalic anhydride (PA) treated IL-4/Luc/CNS-1 transgenic (Tg) HR1 mice (n = 5 per group), subsequent to treatment with acetone-olive oil (AOO), vehicle (DMSO) and two dose MCE (20 and 40 mg/kg) three times a week for 4 weeks. Results MCE treatment reduced the intracellular ROS level (48.2%), NO concentration (7.1 mmol/L) and inflammatory cytokine expressions (39.1%) in the LPS-stimulated RAW264.7 cells. A significant decrease was detected for ear thickness (16.9%), weight of lymph node (0.7 mg), IgE concentration (1.9 µg/mL), and epidermal thickness (31.8%) of the PA + MCE treated Tg mice. MCE treatment induced the decrease of luciferase signal derived from the IL-4 promoter and the recovery of the IL-4 downstream regulator cytokines. PA + MCE treated Tg mice showed decreasing infiltration of mast cells (42.5%), iNOS-mediated COX‐2 induction pathway, MAPK signalling pathway and inflammasome activation in the ear tissue. Conclusions These findings provide the first evidence that MCE may have great potential to suppress chemical-induced skin inflammation through the suppression of IL-4 cytokine and the iNOS-mediated COX‐2 induction pathway, and activation of inflammasome.

Atopic dermatitis is a skin disease characterized by chronic inflammatory lesions, and new therapies are needed to address its rising prevalence. Soy isoflavone has been highlighted as a potential new cosmeceutical material that may have applications in atopic dermatitis care. We have developed a technique to attach an additional -OH group to the ortho position of -OH in the phenol ring using a special enzyme. By adding the -OH group to daidzein, 7,3′,4′-trihydroxyisoflavone can be generated for possible use as a cosmeceutical and functional food material. In this study, we sought to examine the anti-atopic effects of 7,3′,4′-trihydroxyisoflavone, an analog of daidzein. Topical application of 7,3′,4′-trihydroxyisoflavone reduced Dermatophagoides farina extract-induced atopic dermatitis symptoms in NC/Nga mice. Histological analysis demonstrated that 7,3′,4′-trihydroxyisoflavone suppressed D. farina extract-induced infiltration of eosinophils and mast cells into skin lesions. We also found that 7,3′,4′-trihydroxyisoflavone significantly reduces the D. farina extract-induced increases in serum IgE and macrophage-derived chemokine (CCL22) levels. We observed that 7,3′,4′-trihydroxyisoflavone suppresses atopic markers including macrophage-derived chemokine (CCL22) and thymus and activation-regulated chemokine (CCL17) in HaCaT cells. 7,3′,4′-Trihydroxyisoflavone also reduced TNF-α/IFN-γ-induced phosphorylation of ERK1/2 and JNK1/2. These results highlight several desirable properties of 7,3′,4′-trihydroxyisoflavone, which support its use as a cosmeceutical ingredient for the treatment of atopic dermatitis.

Background. The morbidity of eczema has increased in the recent years, and the methods to prevent or ameliorate its effects are becoming more important. To this end, this research was conducted to determine the effectiveness of vitamin supplements in eczema therapy. Method. Embase, PubMed, and Cochrane Central Register of Clinical Trials were searched. Only randomized controlled trials were included, and we included all quantified eligible data where the SCORing Atopic Dermatitis (SCORAD) Index or Eczema Area and Severity Index (EASI) scores were applied to assess the severity of eczema. Results. Ten studies fulfilled the inclusion criteria, and eight of them were included for quantitative analysis (total: 456 patients). Compared to the controls, the SCORAD index or EASI decreased in the vitamin supplement group (mean difference −5.96, 95% CI: −7.69 to −4.23 for vitamin D3; mean difference −5.72, 95% CI: −11.41 to −0.03 for vitamin E; and mean difference −3.19, 95% CI: −4.27 to −2.10 for vitamin B12). Conclusion. This study suggests that vitamin supplements could be important therapeutics to help manage eczema patients.

Background Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by recurring episodes of itchiness with skin erythema and surface damages. Chinese medicine (CM) is widely used for the management of AD in China not only by its own, but also used in combination with conventional therapy (integrated Chinese-Western medicine, ICWM). Although many clinical trials on the effectiveness of ICWM on AD have been conducted, however, up to date, no sound evidence has been established on the clinical effectiveness and safety of ICWM for AD. Objectives To systematically review the currently available clinical evidence on the clinical effectiveness and safety of ICWM for AD. Methods Randomised and quasi-randomised controlled trials, which investigated ICWM interventions with at least one control group using the same conventional interventions, no treatment or placebo treatment, were included. Four English (CENTRAL, MEDLINE, EMBASE, AMED) and three Chinese (CNKI, CBM, WanFang Med) databases were searched. Risk of bias was assessed according to the Cochrane’s tool. Meta-analysis was performed to pool the data. Results From 1473 entries, 55 studies were included, involving 5953 participants aged between 35 days and 67 years old. Duration of treatment ranged from 1 to 24 weeks. Only 2 studies were judged to have low risk of bias, 3 studies had unclear risk of bias, and the other 50 studies were with high risk of bias. ICWM was found to be superior over WM alone in improving clinical severity of AD (measured by EASI, SCORAD), health-related quality of life (measured by CDLQI, DLQI), long term control of AD (recurrence rate), patients/investigator global score (clinical effectiveness rate), and serum IgE level. Adverse events associated with ICWM were found to be comparable with WM alone. Conclusion ICWM seems to produce superior treatment response than WM alone in managing AD without increased risk of adverse events. However, the current available evidence remains too weak to make a conclusive decision.

Prevalence of atopic dermatitis (AD), a chronic, pruritic, and relapsing inflammatory skin disorder, is growing. Because available therapeutics is limited, immune regulators from natural resources could be helpful for treating AD symptoms. The root of Salvia miltiorrhiza Bunge (Lamiaceae) has been studied for the treatment of inflammatory diseases, including dermatologic disorders in Korea. This study examined the effect of salvianolic acid A on AD-like symptoms. Sensitization on the dorsal skin and repeated application on the ears with 2,4-dinitrochlorobenzene (DNCB) were performed in BALB/c mice to induce AD-like skin lesions. After induction of atopic dermatitis, salvianolic acid A (5 and 10 mg/kg) or dexamethasone (10 mg/kg) were administrated via intraperitoneal injection for 3 weeks. Salvianolic acid A suppressed DNCB-induced AD-like symptoms like ear skin hypertrophy and decreased mast cell infiltration into skin lesions. Salvianolic acid A not only reduced DNCB-induced increase of serum IgE but also lowered levels of the Th2 cytokines (IL-4 and IL-13), Th1 cytokine (interferon-γ), and Th17 cytokine (IL-17A). Furthermore, salvianolic acid A blocked DNCB-induced lymph node enlargement. In summary, these results suggest that salvianolic acid A might have a therapeutic potential for the treatment of AD.

The article's abstract is not available.

Portulaca oleracea L. (PO) or Purslane is an annual grassy plant that is distributed in many parts of the world, especially the tropical and subtropical areas. PO has some pharmacological properties such as analgesic, antibacterial, skeletal muscle-relaxant, wound-healing, anti- inflammatory and a radical scavenger. This review article is focused on the anti-inflammatory, immuno-modulatory, anti-oxidant and anti-tumor activities of the PO. Anti-inflammatory, immuno-modulatory, anti-oxidant and Anti-tumor effects of PO were searched using various databases until the end of August 2018. The online literature was searched using PubMed, Science Direct, Scopus, Google Scholar and Web of Science. Our review showed that PO exerts its effects through anti-inflammatory properties and balancing the adaptive and innate immune system depending on situations. PO acts as immune-modulator and anti-oxidant agent in both inflammatory states by the dominance of Th2 response such as asthma, cancer and atopic dermatitis and evoked Th1 disorders including hepatitis and multiple sclerosis.

Background: BIOGF1K, a fraction of Panax ginseng, has desirable antimelanogenic, anti-inflammatory, and antiphotoaging properties that could be useful for treating skin conditions. Because its potential positive effects on allergic reactions in skin have not yet been described in detail, this study's main objective was to determine its efficacy in the treatment of atopic dermatitis (AD). Methods: High-performance liquid chromatography was used to verify the compounds in BIOGF1K, and we used the (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide method to determine its cytotoxicity in RBL-2H3 and HMC-1 cell lines. RBL-2H3 cells were induced using both anti–DNP-IgE/DNP-BSA and calcium ionophore (A2187) treatments, whereas HMC-1 cells were induced using A2187 alone. To measure mast cell degranulation, we performed histamine (enzyme-linked immunosorbent assay) and β-hexosaminidase assays. To quantify interleukin (IL)-4, IL-5, and IL-13 levels in RBL-2H3 cells, we performed quantitative polymerase chain reaction (PCR); to quantify expression levels of IL-4 and IL-13 in HMC-1 cells, we used semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Finally, we detected the total and phosphorylated forms of extracellular signal-regulated kinase, p-38, and c-Jun N-terminal kinase proteins by immunoblotting. Results: BIOGF1K decreased the AD response by reducing both histamine and β-hexosaminidase release as well as reducing the secretion levels of IL-4, IL-5, and IL-13 in RBL-2H3 cells and IL-4 and IL-13 in HMC-1 cells. In addition, BIOGF1K decreased MAPK pathway activation in RBL-2H3 and HMC-1 cells. Conclusions: BIOGF1K attenuated the AD response, hence supporting its use as a promising and natural approach for treating AD. Keywords: Atopic dermatitis, BIOGF1K, Compound K, MAPK, P. ginseng

Pterocarpus santalinus has been traditionally used as a medicinal plant owing to its anti-inflammatory, anthelmintic, tonic, antihyperglycemic, and diaphoretic properties. We hypothesized that P. santalinus might have therapeutic potential in alleviating allergy and atopic dermatitis. Thus, we investigated the inhibitory effects of P. santalinus extract against allergic responses and 2,4-dinitrochlorobenzene-induced atopic dermatitis-like dorsal skin lesions using immunoglobulin E-sensitized rat basophilic leukemia-2H3 mast cells and NC/Nga mice. Degranulation and enzyme-linked immunosorbent assays were conducted to measure degranulation, proinflammatory cytokine levels, and prostaglandin E2 concentrations in immunoglobulin E/antigen-sensitized RBL-2H3 mast cells. The therapeutic efficacy of P. santalinus extract in 2,4-dinitrochlorobenzene-induced atopic dermatitis was evaluated through morphological, physiological, and immunological analysis. P. santalinus extract inhibited β-hexosaminidase and histamine release and reduced tumor necrosis factor-α, interleukin-4, and prostaglandin E2 secretion. Furthermore, P. santalinus extract suppressed atopic dermatitis-like skin lesions by regulating the serum levels of immunoglobulin E and immunoglobulin G2a, and messenger ribonucleic acid expression of T helper cell 1- and T helper cell 2-related mediators in the skin lesions. Histopathological analyses showed a decrease in epidermal thickness and intradermal inflammatory cell infiltration. These results suggested that P. santalinus extract might have beneficial effects in treating allergic and atopic dermatitis-like skin disorders.

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease with an increasing prevalence. In Korea, Jaungo is a traditional medicinal ointment, which is commonly used for treating skin wounds.Thus, we aim to explore the basic clinical efficacy and safety data for Jaungo in patients with AD.This study was a pilot randomized, double-blind, placebo-controlled, single-center trial with three groups. The participants in treatment group 1 applied Jaungo to the lesion twice a day for 3 weeks. Those in treatment group 2 applied Jaungo and placebo ointments to the lesion once a day for 3 weeks. Those in the placebo group applied placebo ointments to the lesion twice a day for 3 weeks. The Eczema Area and Severity Index and SCORing Atopic Dermatitis scores, transepidermal water loss value, and Dermatology Life Quality Index score were assessed. The outcomes used to evaluate safety were the Draize score, blood test results, and expert opinion.In total, 28 patients (82.4%) completed the study. During the study, significant decline of EASI scores in treatment group 2 and placebo group was observed (p 0.05). And there was significant decline of SCORAD scores in treatment group1 and placebo group (p 0.05). Patients in all groups showed decreased TEWL and DLQI scores with no significant difference. There was significant decline of IL-17 in all groups (p 0.05). No serious adverse event was observed.This is the first study that has explored the potential therapeutic effect of Jaungo as a complementary therapy for AD. However, further large study with adjusting placebo ingredients is needed to confirm the effectiveness of Jaungo in patients with chronic-phase AD.

Purpose Rosa davurica Pall., is mainly distributed in Korea, Japan, northeastern China, southeastern Siberia, and eastern Asia. It has been extensively used to treat various kinds of diseases by reason of the significant antioxidant, antiviral and anti-inflammatory activities. However, the pharmacological mechanism of Rosa davurica Pall. in atopic dermatitis (AD) is still ill defined and poorly understood. This study was to examine the anti-inflammatory effects and its mechanism on AD of Rosa davurica Pall. leaves (RDL). Methods To evaluate the therapeutic potential of RDL against AD, we have investigated the effects of RDL on the inflammatory reactions and the productions of inflammatory chemokines and cytokines that were induced by tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) in HaCaT cells. Futhermore, we examined the effects of RDL on the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB). For the in-vivo studies, RDL extract was topically applied to the dinitrochlorobenzene (DNCB)-induced AD mice, then its therapeutic effect was evaluated physiologically and morphologically. Results After the stimulation of HaCaT cells with TNF-α/IFN-γ, RDL considerably reduced the release of inflammatory mediators such as nitric oxide (NO), PEG2 and other cytokines. RDL also reduced the phosphorylations of MAPK and NF-κB in TNF-α/IFN-γ-stimulated HaCaT cells. In vivo topical application of RDL to DNCB-induced AD mice significantly reduced the dorsal skin and ear thickness, clinical dermatitis severity, and mast cells. Treatment with RDL also markedly decreased the levels of serum IgE, IL-6 and the number of WBCs in the blood. Conclusion Our studies indicate that RDL inhibits the AD-like skin lesions by modulating skin inflammation. Consequently, these results suggest that RDL may be served as a possible alternative therapeutic treatment for skin disorder such as AD.

Background Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice. Methods Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate. Results Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups. Conclusion Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

Atopic dermatitis (AD) is a relapsing and remitting chronic inflammatory skin disease for which a variety of etiological factors are involved. Treatment strategies should be multifaceted and have few side effects. In this respect, acupuncture has become increasingly popular as a safe, consistently effective, and drug-free therapy that treats multiple AD symptoms. We aim to not only verify the effectiveness of acupuncture but also suggest patient-specific response determinants and a new underlying mechanism implicating the gut-brain axis. We have designed a randomized, participant-blinded, sham-controlled clinical trial for 60 mild to moderate AD patients. In a previous study, we observed that the clinical skin symptoms of AD were closely associated with gastrointestinal (GI) symptoms. From these findings, we developed an intervention with six acupuncture points: three for AD symptoms and three for GI symptoms. Also, since high responders and low responders to the acupuncture treatment could be identified in the previous study, we now aim to explore response-determining factors, with a particular focus on GI symptoms. Therefore, we will precisely evaluate not only AD symptoms using the SCORAD, EASI, and DLQI tools, but also GI symptoms using the GSRS, TDS, BSFS, and AR tools and abdominal examination. AD develops in association with complicated pathophysiological factors, such as skin barrier function, genetic susceptibility, and immunological factors. Moreover, the underlying mechanism by which acupuncture treatment works has not been clearly elucidated. We, therefore, will conduct a simultaneous cross-sectional study with a sample of 40 healthy individuals, wherein potential indicators, such as fMRI, gut microbiota, and serum TARC and ATX, will be investigated to determine the gut-brain axis-associated mechanism of acupuncture. We expect that the results of this study could provide important clinical evidence for the effects of acupuncture and help elucidate the therapeutic mechanisms that underlie acupuncture’s efficacy in AD treatment. This trial is registered with https://clinicaltrials.gov/ct2/show/KCT0005422 (Trial registration: Korean Clinical Trial Registry (http://cris.nih.go.kr; registration number: KCT0005422); date of registration: September 23, 2020).

Objective Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly caused by immune stimuli. The current study was conducted to investigate the effects of ROCEN and to compare it with betamethasone (Beta) on mice subjected to AD. Methods First, the safety of topical ROCEN was tested to determine possible sensitization induction in vivo. Then, the mice were subjected to oxazolone (Oxa) to induce chronic AD. Consequently, they underwent treatment with ROCEN and Beta. Scratching and wiping behaviors related to dermatitis were evaluated in treated animals for 35 days. The histopathology and immunohistochemistry (IHC) analysis of interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) cytokines were performed on the dorsal skin of the treated mice. Results Topical administration of ROCEN and Beta to the dorsum of sensitized mice for 5 weeks significantly alleviated scratching and wiping symptoms and reduced erythema, scaling, and edema in the skin of the mice with AD. Moreover, histological indices showed that ROCEN effectively reduced leucocyte infiltration and improved skin healing parameters in treated AD mice. Application of ROCEN or Beta reduced IHC markers including IL-8 and TNF-α significantly. Conclusion ROCEN alleviated the AD symptoms similar to betamethasone in an experimental animal model.

Background. The Chinese herbal formula Mamiran cream (MMC) has been known for its ameliorative effects on diverse skin diseases, such as eczema. Atopic dermatitis (AD; eczema) is a chronic recurrent skin disease dominated by T-helper type 2-driven inflammation (Th2). Objective. In this study, the inhibitory effect of MMC on AD was investigated in vivo. Methods. An animal model was established by sensitization with 2,4-dinitrochlorobenzene (DNCB) on the skin of SD rats. Cutaneous administration of MMC was applied, and its mechanism of action was investigated via RT-PCR and IHC assay. Result. Our data showed that topical application of MMC reduced the skin severity scores and alleviated the histological changes. Furthermore, immunohistochemical analysis demonstrated that MMC significantly decreased the levels of Th2 cytokine IL-5 and IL-4Ra in the skin lesion. In addition, it was demonstrated that MMC downregulated the mRNA expression of TNF-α, IL-1β, IL-6, IL-10, and TLR4. Moreover, MMC inhibited the activation of NF-κB, JNK1, and STAT6 pathways in skin lesions. Conclusions. Our findings suggest that MMC exhibits the inhibitory effect on AD, suggesting that MMC may be a potential therapeutic agent for this atopic disorder.

The medicinal herb Centella asiatica (L.) Urban known as gotu kola has been reported to exhibit a wide range of pharmacological activities. In particular, a significant body of scientific research exists on the therapeutic properties of preparations of C. asiatica or its triterpenes in the treatment of skin diseases. The present study is aimed to provide a comprehensive overview of the beneficial effects of C. asiatica on skin diseases. Peer-reviewed articles on the potent dermatological effects of C. asiatica were acquired from PubMed, Web of Science, Scopus, ScienceDirect, and SciFinder. This review provides an understanding of pharmacological studies which confirm the potent dermatological effects and underlying molecular mechanisms of C. asiatica. This medicinal plant and its triterpenes include asiaticoside, madecassoside, and their aglycones, asiatic acid and madecassic acid. These compounds exert therapeutic effects on dermatological diseases such as acne, burns, atopic dermatitis, and wounds via NF-κB, TGF-β/Smad, MAPK, Wnt/β-catenin, and STAT signaling in in vitro and in vivo studies. However, additional rigorously controlled long-term clinical trials will be necessary to confirm the full potential of C. asiatica as a therapeutic agent.

Introduction. Atopic dermatitis (AD) and diarrhea-predominant irritable bowel syndrome (IBS-D) are two recurrent diseases with limited effective treatments. In Chinese Medicine (CM) theory, they may share dampness pattern as the same dominant pathogenesis at a certain stage and, thus, can be treated with the same method. While Chinese herbal formula Huoxiang Zhengqi (HXZQ) has been reported as an effective dampness-resolving therapy for both AD and IBS-D, further high-quality clinical studies are still needed. In addition, HXZQ lacks accurate clinical positioning based on CM patterns. Therefore, we utilize a master protocol design to evaluate HXZQ for dampness pattern simultaneously in AD and IBS-D, with the aim of identifying the pattern-defined population of HXZQ. Methods and Analysis. This master protocol design includes two randomized controlled trials (RCTs) and a real-world observational study. Based on two registry cohorts of AD and IBS-D, patients with dampness pattern will be enrolled in the RCTs to receive either HXZQ oral liquid or a placebo for 4 weeks and then will be followed up for another 4 weeks, while patients with nondampness pattern will constitute the observational study and experience a 12-week follow-up. A total of 678 AD patients and 322 IBS-D patients will be recruited from 14 hospitals in China over a 3-year period. The eczema area and severity index (EASI) and the proportion of responders for adequate relief (AR) are the primary outcomes in AD and IBS-D, respectively. Analysis will be undertaken separately in each substudy, and then an overall analysis combining multiple subgroups will be performed to comprehensively investigate the effect of HXZQ. Discussion. This study will provide high-quality efficacy evidence of HXZQ for AD and IBS-D patients and give an example of postmarketing evaluation for CM products under the pattern dominating different disease research model. The study is registered with ChiCTR1900026700 and ChiCTR1900026837.

Background Atopic dermatitis (AD) is a worldwide chronic skin disease which burden public health. Sea buckthorn (SBT) (Hippophae rhamnoides L., Elaeagnaceae) oil, as a traditional herbal medicine, has been used for disease treatment for many years. The effects of SBT oil on AD mouse model induced by repeated administration of 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice was evaluated in this study. Methods Mice were divided into four groups including the normal control group, AD model group, AD model group treated with SBT oil (5 ml/kg) and AD model group treated with SBT oil (10 ml/kg). Same volume at different concentrations of SBT oil was applied daily on the latter two groups by gavage for 15 days following AD model induction. The function of skin barrier and the production of IL-4, IFN-γ, TNF-α and TSLP were examined after animal sacrifice. The migration and mature of langerhans cell (LCs) in lymph node was further assessed by flow cytometry. Results SBT oil alleviated dermatitis scores, decreased ear thickness, prevented infiltration of mast cell, reduced lymph node weight and depressed activity of Th2 cells. SBT oil also reduced the expression of IL-4, IFN-γ, TNF-α and TSLP in ear tissue, IgE level in serum and mRNA relative expression of IL-4, IFN-γ, TNF-α in lymph node. Moreover, SBT oil inhibited the migration of LCs cells from local lesions to lymph node and it’s mature in lymph node. Conclusions These results suggest SBT oil had a beneficial effect either systemic or regional on DNCB-induced AD mice via maintain the balance of Th1/Th2 and may be a potential complementary candidate for AD treatment.

Background Atopic dermatitis is a chronic inflammatory skin disease in humans. Although Olea europaea leaf extract (OLE) and Spirodela polyrhiza extract (SPE) have been used to protect against skin damage, the effects of their combined administration on atopic dermatitis have yet to studied. Purpose In this study, we evaluated the potential therapeutic effects of an OLE and SPE combination on the progression of atopic dermatitis and the possible mechanisms underlying these effects in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. Methods Atopic dermatitis was induced by topical application of 0.2% w/v DNCB prepared in an olive oil:acetone solution (1:3), and thereafter OLE, SPE and OLE + SPE were administered orally for 5 weeks. We determined atopic dermatitis symptoms, serum IgE levels, and levels of cytokine- and gene expression in the dorsal skin and splenocytes, and performed histological and immune cell subtype analyses. The expression of skin barrier-related proteins (filaggrin, sirtuin 1, and claudin 1) was also evaluated. Results The OLE + SPE combination significantly ameliorated atopic dermatitis symptoms, including dermatitis scores, and reduced epidermal thickness and infiltration of different inflammatory cells in mice with DNCB-induced atopic dermatitis. It also significantly reduced the number of CD4+, CD8+, and CD4+/CD69+ T cells; immunoglobulin E-producing B cells (CD23+/B220+) in the axillary lymph nodes; CD3+ T-cell eosinophils (chemokine–chemokine receptor 3+/CD11b+) in the skin; and CD3+ T cells, immunoglobulin E-producing B cells (CD23+/B220+), and eosinophils in peripheral blood mononuclear cells. Additionally, the experimental combination lowered levels of serum immunoglobulin E and histamine, as well as Th2-mediated cytokines, and interleukin-4, -5, and -13, whereas it increased the levels of Th1-mediated cytokine interferon-γ in splenocytes. Furthermore, the preparation significantly restored expression of the skin barrier-related proteins filaggrin, sirtuin 1, and claudin 1, and also reduced the expression of the inflammatory cytokine interleukin-6 and chemokine–chemokine receptor 3, as well as the pruritus-related cytokine interleukin-31 and interleukin-31 receptor, in atopic dermatitis skin lesions. Conclusion Taken together, our findings indicate that administration of a combination of OLE and SPE can alleviate atopic dermatitis symptoms by regulating immune balance and skin barrier function and may be an effective therapeutic option for the treatment of atopic dermatitis.

Genetics and prenatal environmental exposures are indicated in the complex etiopathogenesis and clinical expression of atopic diseases. This study examined the clinical features of infantile-onset atopic dermatitis (AD) in relation to maternal diet during pregnancy.Maternal dietary habits were evaluated in terms of the frequency of intake of six different food categories rich in antioxidants or omega-3 fatty acids.One hundred mother-child pairs were recruited, 47 infants (12 months) and 53 children aged 12-36 months. Forty-six of the children had mild, 41 moderate and 13 severe AD. The other atopic manifestations (alone or associated) included: asthma in 9 cases, allergic rhinitis in 22 cases and food allergy in 33 cases. The presence of asthma in children was significantly associated with a lower level of maternal dietary intake of fruits and vegetables as well as chocolate confectionery, while associations with whole grain breakfast cereals, nuts and seeds, non-alcoholic beverages (coffee, tea, fruit juices) and fish and fish products, were not statistically significant. The age of onset and severity of infantile-onset AD were not linked to any of the food categories considered for analyses.Healthy diet in pregnant women that is rich especially in antioxidants may provide protection against atopic comorbidities of AD. Further prospective reasearch on the role of maternal diet in primary prevention of atopic diseases is warranted.

Objectives Evidence suggests that cannabinoids may provide therapeutic benefit to patients with dermatologic conditions. The recommendation behaviors of dermatologists with regards to recommending medical cannabis are unknown. We administered a pilot survey to evaluate dermatologists’ recommendation behaviors including dermatologic indications and formulation preferences. Design A cross-sectional study was done to sample dermatologists using a 24-question survey. Setting Online survey through SurveyMonkey® that was distributed via Orlando Dermatology Aesthetic and Clinical Conference’s mailing list, including thousands of practicing dermatologists. Main outcome measures Descriptive data of dermatologists’ recommendation behaviors of medical cannabis are described. Fisher’s exact test and Chi-Square tests were used to compare recommendation behaviors by gender, age, years in practice, and residency legality. Results The survey was sent to 7176 individuals; of the 28.7 % who opened the email, 2.2 % completed the survey (N = 145). 91 % of dermatologists were in support of medical cannabis use and 13.8 % have recommended it for a dermatologic condition. Atopic dermatitis (45 %) and psoriasis (40 %) were the most common. The most common form of administration was topical (75 %). The main reasons for not recommending medical cannabis were limited knowledge (56 %) and lack of experience (48 %). Conclusions Cutaneous inflammatory and pruritic conditions such as psoriasis and atopic dermatitis were the most common reasons dermatologists recommended medical cannabis in our survey. Respondents’ recommendation patterns may have been limited by limited by lack of knowledge or experience with medical cannabis. The small sample size of our survey limits generalizability to the dermatology field and warrants further investigation.

Background and Objective. The topical human milk (THM) is one of the traditional remedies for various cases of injuries, ulcers, and infections for decades. No study was found reporting the adverse effects of human milk. The current study reviews the anti-inflammatory properties of human milk when topically applied to dermal and optical diseases. Methods. The various datasets including Ovid, PubMed, Google Scholar, Science Direct, Magiran, Irandoc, SID, and IranMedex were searched from 1990 to 2018. From the 119 reviewed articles, 20 articles were selected to be included in the current article. Results. There is a consensus among the literature and ancient texts regarding the effectiveness of THM in curing the various types of skin damages, such as cord separation, atopic dermatitis, diaper dermatitis, conjunctivitis, scratches, insect bite, perineal ulcer, and nipple ulcer. However, the importance of its application has not been given much attention. Conclusion. According to the information obtained from the articles reviewed, the THM appears to be an effective, safe, and available treatment compared to conventional chemical treatments. This study suggests THM as an alternative remedy to minimize the frequent use of chemical-based treatments. More research may be beneficial to reach certainty in terms of curative properties of THM in similar or different injuries in different populations.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by intense pruritus and skin lesions. The exact cause of AD is not yet known and the available therapeutic strategies for AD are limited. Fructus cnidii is commonly used in traditional Chinese medicine as an herb for treating chronic itch. However, the mechanism underlying the antipruritic effects of Fructus cnidii is not well understood. In the present study, we investigated the antipruritic effect of locally administered ethyl acetate extract from Fructus cnidii (EAEFC) to 2,4-dinitrofluorobenzene- (DNFB-) induced AD in a mouse model. The scratching behavior, skin thickness, dermatitis score, weight, blood immunoglobulin E (IgE) level, and itch-related cytokine levels were subsequently monitored and evaluated. Results showed that EAEFC treatment attenuated the DNFB-induced AD-like symptoms by alleviating the skin lesions and decreasing the dermatitis score. Hematoxylin and eosin (H&E) and toluidine blue (TB) staining analyses demonstrated that EAEFC mitigated the DNFB-induced increase in skin thickness and prevented the infiltration of mast cells. Behavioral tests showed that EAEFC decreased the DNFB-induced acute and chronic scratching behaviors. Furthermore, EAEFC reduced the levels of itch-related cytokines, such as thymic stromal lymphopoietin (TSLP), interleukin- (IL-) 17, IL-33, and IL-31, and the DNFB-induced boost in serum IgE. Collectively, these results suggest that EAEFC is a potential therapeutic candidate for the treatment of chronic itch in AD.