Search Results (92)

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

Perfluorononanoic acid (PFNA) is a ubiquitous persistent environmental pollutant, and several studies have found significant links between atopic dermatitis (AD) and prenatal exposure to PFNA. However, the relationship between PFNA and AD remains unclear. In this study, 2,4-dinitrochlorobenzene (DNCB)-treated female BALB/c mice were used as AD models to investigate the effects of PFNA and its potential mechanisms. These mice were topically applied with 5 mg/kg PFNA per day for 15 days. The results demonstrated that PFNA significantly increased AD lesion severity and clinical symptoms, including dermatitis score, ear thickness, and epidermal thickness. In addition, PFNA also increased the serum IgE level, splenic atrophy, and upregulated the expression of TNF-α, IL-6, and IL-1β, genes that are associated with skin inflammatory factors. In addition, Western blot results showed that PFNA treatment upregulated the expression of p-JNK protein. Additionally, cellular experiments indicated that RAW264.7 macrophages and mouse brain microvascular endothelial (bEnd.3) cells treated with PFNA at concentrations of 0.01–100 μM for 72 h showed no changes in cell viability. However, 100 μM PFNA upregulated the mRNA expression levels of the pro-inflammatory cytokines IL-1β and IL-6, as well as the protein expression of p-JNK, in RAW264.7 cells induced with 1 mg/mL LPS for 2 h. Similarly, PFNA increased TNF-α and IL-6 mRNA expression and p-JNK protein expression in bEnd.3 cells stimulated with 20 ng/mL TNF-α for 0.5 h. Based on these findings, we can conclude that PFNA may aggravate atopic dermatitis by promoting inflammation. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease stemming from genetic susceptibility and environmental factors. It is characterized by immune dysregulation, increased mast cell activity, elevated levels of immunoglobulin E (IgE), and excessive proinflammatory mediator expression. These factors contribute to hallmark symptoms such as pruritus, erythema, and skin barrier dysfunction. In this study, we investigated the antioxidant and anti-inflammatory effects of Taraxacum mongolicum (WTM) water extract, as well as its skin barrier regulation and immune functions in AD. In the present study, we explored the therapeutic efficacy and underlying mechanisms of WTM in a BALB/c mouse model of AD induced by 2,4-dinitrochlorobenzene (DNCB). Mice were administered WTM orally or topically for 14 consecutive days. The results demonstrated that WTM treatment significantly alleviated clinical severity, showing reductions in skin lesion scores, epidermal thickness, mast cell infiltration, and scratching behavior, compared to the DNCB-treated group. Mechanistically, WTM reduced serum levels of IgE and proinflammatory cytokines (IL-4, IL-6, IL-1β, TNF-α, and IL-31) while suppressing the expression of the JAK/STAT/TSLP signaling pathway in skin tissues. Furthermore, WTM inhibited the TLR4/NF-κB and MAPK pathways and enhanced antioxidant defense by elevating superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. These findings indicate that WTM attenuates DNCB-induced AD progression in mice, likely through the dual modulation of inflammatory signaling and oxidative stress. These findings suggest that WTM may modulate the immune response and alleviate AD symptoms by inhibiting the TLR4/NF-κB, MAPK, and JAK/STAT/TSLP pathways. Full article

Atopic dermatitis (AD) is a common chronic skin disease affecting both children and adults. Currently lacking a clinical cure, AD presents significant physical and emotional challenges for patients and their families, substantially impacting their quality of life. This underscores significant unmet needs in AD management and highlights the necessity for developing effective therapeutic applications. Recently, several chlorine-containing active substances with promising pharmacological activity have been discovered in soft corals cultivated through coral farming. Among these, brianolide, isolated from the soft coral Briareum stechei, has shown promising potential. This study investigated brianolide’s regulatory effects on the inflammatory response in atopic dermatitis and its underlying mechanisms. Using an in vitro human keratinocyte cell line (HaCaT) stimulated with tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) to mimic AD inflammation, brianolide was found to inhibit cytokine and chemokine expression via the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB)-signaling pathways. In an in vivo animal model of 2,4-Dinitrochlorobenzene (DNCB)-induced AD, brianolide demonstrated anti-inflammatory effects, reducing transepidermal water loss (TEWL), ear thickness, erythema, and epidermal blood flow. These findings provide new insights into brianolide’s activity against AD-related inflammation, elucidate potential mechanisms, and contribute to understanding the pharmacological potential of natural coral products for AD treatment. Full article

Background: Chronic pruritus and inflammatory skin lesions, characterized by high recurrence, are hallmarks of atopic dermatitis (AD). Despite its increasing prevalence, the development of therapeutic agents for AD remains limited. This study aimed to evaluate the therapeutic effects of deep sea minerals (DSMs) in mist and cream formulations on the development of AD-like skin lesions in NC/Nga mice exposed to either Dermatophagoides farinae body extract (Dfb) or 2,4-dinitrochlorobenzene (DNCB). Methods: To induce AD, 100 mg of Biostir AD cream containing crude Dfb or 200 µL of DNCB (1%) was topically applied to the dorsal skin of NC/Nga mice. Additionally, 200 µL of deep sea mineral mist (DSMM) and 10 mg of deep sea mineral cream (DSMC) were applied daily to the dorsal skin for 4 weeks. AD was assessed through visual observations, clinical scoring of skin severity, serological tests, and histological analysis. Results: Visual and clinical evaluations revealed that DSMs inhibited the formation of AD-like skin lesions. DSMs also significantly affected trans-epidermal water loss and erythema. Treatment with DSMs resulted in reduced serum levels of IgE, IFN-γ, and IL-4. Histological analysis indicated that DSMs decreased skin thickness. Immunostaining for the CD4 antigen demonstrated a reduced infiltration of CD4⁺ T cells, which drive the Th2 response in AD, following DSM treatment. Conclusions: In conclusion, the cream formulation of DSMs showed better results than the mist formulation. These results suggest that DSMs may be an effective treatment for AD-like skin lesions, especially in cream formulation. Full article

Background: Cannabis sativa L. and its products are becoming popular for the treatment of inflammatory diseases. One of the main phytocannabinoids contained in cannabis is cannabidiol (CBD), which is a component of numerous cosmetic preparations used to treat inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. However, current data regarding the efficacy and safety of CBD for dermatological indications are limited. Therefore, the aim of the present study was to evaluate the anti-inflammatory effect of high-CBD Cannabis sativa L. extract (eCBD) in a model of AD. Methods: Dermatitis was induced by repeated application of 2,4-dinitrochlorobenzene (DNCB) to the skin of the rats’ ears. The therapeutic effect of eCBD was evaluated in behavioral, histopathological, and hematological studies following topical application as an ointment containing 2% CBD. Results: Application of the ointment containing eCBD resulted in attenuation of DNCB-induced inflammation. Interestingly, an anti-edematous effect was more pronounced in rats treated with the eCBD than in rats treated with 1% hydrocortisone ointment. However, eCBD did not reduce the frequency of DNCB-induced scratching, while there was a visible antipruritic effect of 1% hydrocortisone application. Histopathological analysis revealed that both eCBD and 1% hydrocortisone ointments significantly decreased mast cell count compared with the Vaseline control group. Furthermore, treatment with an ointment containing eCBD resulted in a decrease in the number of leukocytes in the blood. Conclusions: Topically administered eCBD had a stronger anti-edematous effect than glucocorticosteroid and differently affected hematological parameters. It is suggested that eCBD has therapeutic potential for the treatment of AD. Full article

The discovery of effective cysteine protease inhibitors with crude protein kiwi extracts (CPKEs) has created novel challenges and prospects for pharmaceutical development. Despite extensive research on CPKEs, limited research has been conducted on treating atopic dermatitis (AD). Therefore, the objective of this work was to investigate the anti-inflammatory effects of CPKEs on TNF-α activation in a HaCaT cell model and in a DNCB (1-chloro-2, 4-dinitrochlorobenzene)-induced atopic dermatitis animal model. The molecular weight of the CPKE was determined using SDS-PAGE under non-reducing (17 kDa and 22 kDa) and reducing conditions (25 kDa, 22 kDa, and 15 kDa), whereas gelatin zymography was performed to examine the CPKE’s inhibitory impact on cysteine protease (actinidin and papain) activity. Moreover, the CPKE remains stable at 60 °C, with pH levels varying from 4 to 11, as determined by the azocasein assay. CPKE treatment decreased the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, along with the activation of nuclear factor-kappa B (NF-κB)-p65 in tumor necrosis factor-α (TNF-α)-stimulated HaCaT cells. Five-week-old BALB/c mice were treated with DNCB to act as an AD-like animal model. The topical application of CPKE to DNCB-treated mice for three weeks substantially decreased clinical dermatitis severity and epidermal thickness and reduced eosinophil infiltration and mast cells into ear and skin tissues. These findings imply that CPKE derived from kiwifruit might be a promising therapy option for inflammatory skin diseases such as AD. Full article

Cannabichromene (CBC) is one of the main cannabinoids found in the cannabis plant, and although less well known than tetrahydrocannabinol (THC) and cannabidiol (CBD), it is gaining attention for its potential therapeutic benefits. To date, CBC’s known mechanisms of action include anti-inflammatory, analgesic, antidepressant, antimicrobial, neuroprotective, and anti-acne effects through TRP channel activation and the inhibition of inflammatory pathways, suggesting that it may have therapeutic potential in the treatment of inflammatory skin diseases, such as atopic dermatitis (AD), but its exact mechanism of action remains unclear. Therefore, in this study, we investigated the effects of CBC on Th2 cytokines along with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways involved in AD pathogenesis. We used a 2,4-Dinitrochlorobenzene (DNCB)-induced BALB/c mouse model to topically administer CBC (0.1 mg/kg or 1 mg/kg). The results showed that skin lesion severity, ear thickness, epithelial thickness of dorsal and ear skin, and mast cell infiltration were significantly reduced in the 0.1 mg/kg CBC-treated group compared with the DNCB-treated group (p < 0.001). In addition, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed a significant decrease in the mRNA expression of Th2 cytokines (TSLP, IL-4, IL-13) and inflammatory mediators (IFN-γ, IL-1β, IL-6, IL-17, IL-18, and IL-33) (p < 0.05). Western blot analysis also revealed a significant decrease in JAK1, JAK2, STAT1, STAT2, STAT3, and STAT6 protein expression (p < 0.05). These results suggest that CBC is a promising candidate for the treatment of AD and demonstrates the potential to alleviate AD symptoms by suppressing the Th2 immune response. Full article

Patchouli oil (PO) is a natural substance famous for its immune-enhancing and anti-inflammatory effects. Atopic dermatitis (AD) is characterized by epidermal gene mutations, skin barrier dysfunction, and immune dysregulation, making patchouli volatile oil a potential candidate for AD treatment. Initially, PO was mixed with ethyl oleate (EO), castor oil ethoxylated ether-40 (EL-40), anhydrous ethanol, and water to form a patchouli oil microemulsion (PO-ME) system. The formulation ratios were optimized using the Box–Behnken design-effect surface method, and their products were characterized for type, particle size, polydispersity index (PDI), and appearance. Additionally, patchouli oil microemulsion gel (PO-MEG) was developed with a specified concentration of 1.5% carbomer-940 as the matrix, and its pH, stability, viscosity, and permeability were evaluated. We assessed the irritation tests of PO-MEG using a rat self-control model and the Cell Counting Kit-8 (CCK-8) assay. The results demonstrated that should be attributed to non-irritating. This study also assessed the efficacy of optimized PO-MEG on AD-like symptoms using a 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mouse model. Compared with the model group, the in vivo efficacy studies have shown the PO-MEG group significantly reduces dermatitis scores, mast cell counts, epidermal thickness, and levels of pro-inflammatory cytokines and immune factors in skin homogenates. This suggests that PO-MEG would become a safer topical formulation for treating atopic dermatitis. Full article

Silica (SiO₂), titanium dioxide (TiO₂), and zinc oxide (ZnO) nanoparticles (NPs) are widely used in dermal products. Their skin sensitization potential, especially their effects in combination with known sensitizers, is poorly studied in vitro and their sensitization inconsistently reported in animal studies. In this study, cellular assays were used to identify different steps of sensitization, the activation of keratinocytes and dendritic cells, when cells were exposed to these NPs in the absence and presence of sensitizers. Cellular systems included HaCaT keratinocytes and U937 (U-SENS™) alone, as well as different co-culture systems of THP-1 cells with HaCaT cells (COCAT) and with primary keratinocytes. The effect of NPs differed between co-cultures and U-SENS™, whereas co-cultures with either primary keratinocytes or HaCaT cells responded similarly. Pre-exposure to ZnO NPs increased the U-SENS™ assay response to 2,4-dinitrochlorobenzene six-fold. The COCAT increase was maximally four-fold for the combination of SiO₂ and trans cinnamaldehyde. When the THP-1 cells were separated from the keratinocytes by a membrane, the response of the co-culture system was more similar to U-SENS™. The direct contact with keratinocytes decreased the modulating effect of TiO₂ and ZnO NPs but suggested an increase in response to sensitizers following dermal contact with SiO₂ NPs. Full article

We aimed to evaluate the effect of black soybean extract cream (BSEC) on 2,4-dinitrochlorobenzene (DNCB)-induced dermatitis in murine models mimicking inflammatory dermatitis observed in humans. In this DNCB-induced model, BALB/c mice were spread with 100 μL of 2% DNCB twice a week for two weeks to induce skin inflammation on the shaved back skin; then, a placebo or BSEC that consisted of the volatile fraction derived from the seeds of Glycine max (L.) Merr. was applied to the DNCB-sensitized mice for 7 days. Gross visual analysis was conducted to assess the impact of BSEC on dermatitis, and an enzyme-linked immunosorbent assay (ELISA) was subsequently performed to detect inflammatory cytokines in the presence or absence of BSEC after DNCB sensitization. Lastly, the possible mechanisms responsible for the effects of BSEC on inflammatory dermatitis were investigated in a human leukemia monocytic cell line, THP-1. Our study showed that BSEC displayed antioxidant and anti-inflammatory effects. BSEC has the ability to diminish dermatitis, and all three experiments demonstrated that BSEC effectively reduced the progression of dermatitis while significantly suppressing inflammatory responses in the preclinical models. Consequently, BSEC exhibited promising phytotherapy for inflammatory dermatitis, potentially attributed to its anti-inflammatory and antioxidant properties. Full article

As it has been revealed that the activation of human immune cells through the activity of intestinal microorganisms such as pro- and prebiotics plays a vital role, controlling the proliferation of beneficial bacteria and suppressing harmful bacteria in the intestine has become essential. The importance of probiotics, especially for skin health and the immune system, has led to the emergence of products in various forms, including probiotics, prebiotics, and parabiotics. In particular, atopic dermatitis (AD) produces hypersensitive immunosuppressive substances by promoting the differentiation and activity of immune regulatory T cells. As a result, it has been in the Th1 and Th2 immune balance through a mechanism that suppresses skin inflammation or allergic immune responses caused by bacteria. Furthermore, an immune mechanism has recently emerged that simultaneously controls the expression of IL-17 produced by Th17. Therefore, the anti-atopic effect was investigated by administering doses of anti-atopic candidate substances (Lactobacilus sakei CVL-001, Lactobacilus casei MCL, and Lactobacilus sakei CVL-001 Lactobacilus casei MCL mixed at a ratio of 4:3) in an atopy model using 2,4-dinitrochlorobenzene and observing symptom changes for 2 weeks to confirm the effect of pro-, para-, and mixed biotics on AD. First, the body weight and feed intake of the experimental animals were investigated, and total IgG and IgM were confirmed through blood biochemical tests. Afterward, histopathological staining was performed using H&E staining, Toluidine blue staining, Filaggrin staining, and CD8 antibody staining. In the treatment group, the hyperproliferation of the epidermal layer, the inflammatory cell infiltration of the dermal layer, the expression of CD8, the expression of filaggrin, and the secretion of mast cells were confirmed to be significantly reduced. Lastly, small intestine villi were observed through a scanning microscope, and scoring evaluation was performed through skin damage. Through these results, it was confirmed that AD was reduced when treated with pro-, para-, and mixed biotics containing probiotics and parabiotics. Full article

Filaggrin (FLG) is an essential structural protein expressed in differentiated keratinocytes. Insufficient FLG expression contributes to the pathogenesis of chronic inflammatory skin diseases. Saikosaponin A (SSA), a bioactive oleanane-type triterpenoid, exerts anti-inflammatory activity. However, the effects of topically applied SSA on FLG expression in inflamed skin remain unclear. This study aimed to evaluate the biological activity of SSA in restoring reduced FLG expression. The effect of SSA on FLG expression in HaCaT cells was assessed through various biological methods, including reverse transcription PCR, quantitative real-time PCR, immunoblotting, and immunofluorescence staining. TNFα and IFNγ decreased FLG mRNA, cytoplasmic FLG protein levels, and FLG gene promoter–reporter activity compared to the control groups. However, the presence of SSA restored these effects. A series of FLG promoter–reporter constructs were generated to investigate the underlying mechanism of the effect of SSA on FLG expression. Mutation of the AP1-binding site (mtAP1) in the −343/+25 FLG promoter–reporter abrogated the decrease in reporter activities caused by TNFα + IFNγ, suggesting the importance of the AP1-binding site in reducing FLG expression. The SSA treatment restored FLG expression by inhibiting the expression and nuclear localization of FRA1 and c-Jun, components of AP1, triggered by TNFα + IFNγ stimulation. The ERK1/2 mitogen-activated protein kinase signaling pathway upregulates FRA1 and c-Jun expression, thereby reducing FLG levels. The SSA treatment inhibited ERK1/2 activation caused by TNFα + IFNγ stimulation and reduced the levels of FRA1 and c-Jun proteins in the nucleus, leading to a decrease in the binding of FRA1, c-Jun, p-STAT1, and HDAC1 to the AP1-binding site in the FLG promoter. The effect of SSA was evaluated in an animal study using a BALB/c mouse model, which induces human atopic-dermatitis-like skin lesions via the topical application of dinitrochlorobenzene. Topically applied SSA significantly reduced skin thickening, immune cell infiltration, and the expression of FRA1, c-Jun, and p-ERK1/2 compared to the vehicle-treated group. These results suggest that SSA can effectively recover impaired FLG levels in inflamed skin by preventing the formation of the repressor complex consisting of FRA1, c-Jun, HDAC1, and STAT1. Full article

The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin’s reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1β) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin’s response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP. Full article

Atopic dermatitis (AD) is a chronic skin condition that is characterized by dysregulated immune responses and a heightened risk of Staphylococcus aureus infections, necessitating the advancement of innovative therapeutic methods. This study explored the potential of (6Z,9Z,12Z,15Z)-(2R,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl octadeca-6,9,12,15-tetraenoate (HSN-S1), a compound derived from the marine alga Hizikia fusiformis, which shows anti-inflammatory, antimicrobial, and immunomodulatory properties. HSN-S1 was isolated and characterized using advanced chromatographic and spectroscopic methods. Its efficacy was evaluated via in vitro assays with keratinocytes, macrophages, and T cells to assess cytokine suppression and its immunomodulatory effects; its antibacterial activity against S. aureus was quantified. The in vivo effectiveness was validated using a 2,4-dinitrochlorobenzene-induced AD mouse model that focused on skin pathology and cytokine modulation. HSN-S1 significantly reduced pro-inflammatory cytokine secretion, altered T-helper cell cytokine profiles, and showed strong antibacterial activity against S. aureus. In vivo, HSN-S1 alleviated AD-like symptoms in mice and reduced skin inflammation, transepidermal water loss, serum immunoglobulin-E levels, and Th2/Th17 cytokine outputs. These findings suggest HSN-S1 to be a promising marine-derived candidate for AD treatment, as it offers a dual-target approach that could overcome the limitations of existing therapies, hence warranting further clinical investigation. Full article