scholarly journals Impressic Acid Ameliorates Atopic Dermatitis-Like Skin Lesions by Inhibiting ERK1/2-Mediated Phosphorylation of NF-κB and STAT1

2021 ◽  
Vol 22 (5) ◽  
pp. 2334
Author(s):  
Jae Ho Choi ◽  
Gi Ho Lee ◽  
Sun Woo Jin ◽  
Ji Yeon Kim ◽  
Yong Pil Hwang ◽  
...  

Impressic acid (IPA), a lupane-type triterpenoid from Acanthopanax koreanum, has many pharmacological activities, including the attenuation of vascular endothelium dysfunction, cartilage destruction, and inflammatory diseases, but its influence on atopic dermatitis (AD)-like skin lesions is unknown. Therefore, we investigated the suppressive effect of IPA on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin symptoms in mice and the underlying mechanisms in cells. IPA attenuated the DNCB-induced increase in the serum concentrations of IgE and thymic stromal lymphopoietin (TSLP), and in the mRNA levels of thymus and activation regulated chemokine(TARC), macrophage derived chemokine (MDC), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) in mice. Histopathological analysis showed that IPA reduced the epidermal/dermal thickness and inflammatory and mast cell infiltration of ear tissue. In addition, IPA attenuated the phosphorylation of NF-κB and IκBα, and the degradation of IκBα in ear lesions. Furthermore, IPA treatment suppressed TNF-α/IFN-γ-induced TARC expression by inhibiting the NF-κB activation in cells. Phosphorylation of extracellular signalregulated protein kinase (ERK1/2) and the signal transducer and activator of transcription 1 (STAT1), the upstream signaling proteins, was reduced by IPA treatment in HaCaT cells. In conclusion, IPA ameliorated AD-like skin symptoms by regulating cytokine and chemokine production and so has therapeutic potential for AD-like skin lesions.

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4409
Author(s):  
Jinjoo Kang ◽  
Soyoung Lee ◽  
Namkyung Kim ◽  
Hima Dhakal ◽  
Taeg-Kyu Kwon ◽  
...  

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1127
Author(s):  
Juan Sendon-Lago ◽  
Lorena Garcia-del Rio ◽  
Noemi Eiro ◽  
Patricia Diaz-Rodriguez ◽  
Leandro Avila ◽  
...  

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly prevalent and current therapies are not completely effective. Mesenchymal stem cells are emerging as a promising therapeutic option. Here, the effect of local hydrogel application loaded with conditioned medium (CM) from human uterine cervical stem cells (hUCESC-CM) in an experimental acute colitis mice model has been evaluated. Colitis induction was carried out in C57BL/6 mice by dissolving dextran sulfate sodium (DSS) in drinking water for nine days. Ulcers were treated by rectal administration of either mesalazine (as positive control) or a mucoadhesive and thermosensitive hydrogel loaded with hUCESC-CM (H-hUCESC-CM). Body weight changes, colon length, and histopathological analysis were evaluated. In addition, pro-inflammatory TNF-α, IL-6, and IFN-γ mRNA levels were measured by qPCR. Treatment with H-hUCESC-CM inhibited body weight loss and colon shortening and induced a significant decrease in colon mucosa degeneration, as well as TNF-α, IFN-γ, and IL-6 mRNA levels. Results indicate that H-hUCESC-CM effectively alleviated DSS-induced colitis in mice, suggesting that H-hUCESC-CM may represent an attractive cell-free therapy for local treatment of IBD.


Planta Medica ◽  
2019 ◽  
Vol 86 (03) ◽  
pp. 190-197
Author(s):  
Sang Hun Park ◽  
Chang Hyung Lee ◽  
Ji Yun Lee ◽  
Hee Yang ◽  
Jong Hun Kim ◽  
...  

AbstractAtopic 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.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1657 ◽  
Author(s):  
Yun-Mi Kang ◽  
Kyou-Young Lee ◽  
Hyo-Jin An

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex symptoms. To treat AD without adverse effects, alternative therapeutic agents are required. The tubers of Helianthus tuberosus L. (Jerusalem artichoke) have been used in folk remedies for diabetes and rheumatism. However, its effect on AD development remains unknown. Therefore, this study examined the inhibitory effect of H. tuberosus (HT) on AD skin symptoms using an NC/Nga mouse model and HaCaT keratinocytes. The effect of HT and associated molecular mechanisms were evaluated in Dermatophagoides farina body (Dfb)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes by ELISA, western blot, and histological analysis. Topical HT administration attenuated AD skin symptoms in Dfb-induced AD mice, with a significant reduction in the dermatitis score and production of inflammatory mediators. HT also decreased epidermal thickness and mast cell infiltration. Moreover, HT restored filaggrin expression and inhibited adhesion molecules in the mice. These effects were confirmed in vitro. Furthermore, HT suppressed the activation of NF-κB, Akt, and mitogen-activated protein kinase (MAPK) signaling pathways induced by TNF-α/IFN-γ. These results suggest that HT is a potential therapeutic agent or supplement for skin allergic inflammatory diseases such as AD.


Author(s):  
Jian Wang ◽  
Gang Li ◽  
Haixiu Zhang ◽  
Ying Xie

Abstract Atopic dermatitis (AD) is a serious inflammatory condition associated with severe itching and persistent eczematous lesion. Therefore, the present study was intended to scrutinize the beneficial effect of Luteolin (LT) on the atopic dermatitis murine model. The effect of LT was investigated on the various parameters, such as oxidative stress and inflammation after induction of AD. The serum level of IgE, and cells of the WBC family (neutrophils, basophils, eosinophils, monocytes, lymphocytes, and total WBC) and histopathological analysis of skin tissue were also examined to confirm the effect of LT. Results of the study suggested that LT significantly inhibited the elevated IgE level together with improvement in injured skin tissue architecture. It also reduces oxidative stress (MDA, SOD, and GSH) and inflammation (IL-1β, IL-6, TNF-α, IFN-γ, IL-4, and IL-17A) as evidenced by ELISA analysis. The level of examined WBC family cells was found reduced significantly as compared to the AD model group. In western blot analysis, LT showed significant down-regulation of NF-ĸB and TLR-4. Collectively, our results suggest that LT can effectively reverse the effect of atopic dermatitis via improving immunological response.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2448
Author(s):  
Gyo-Ha Moon ◽  
Yonghyeon Lee ◽  
Eun-Kyung Kim ◽  
Kang-Hyun Chung ◽  
Kwon-Jai Lee ◽  
...  

We examined the immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in atopic dermatitis (AD). AA treatment (5–20 µg/mL) dose-dependently suppressed the tumor necrosis factor (TNF)-α level and interleukin (IL)-6 protein expression in interferon (IFN)-γ + TNF-α-treated HaCaT cells. The 2,4-dinitrocholrlbenzene (DNCB)-induced AD animal model was developed by administering two AA concentrations (30 and 75 mg/kg/d: AD + AA-L and AD + AA-H groups, respectively) for 18 days. Interestingly, AA treatment decreased AD skin lesions formation and affected other AD characteristics, such as increased ear thickness, lymph node and spleen size, dermal and epidermal thickness, collagen deposition, and mast cell infiltration in dorsal skin. In addition, in the DNCB-induced AD animal model, AA treatment downregulated the mRNA expression level of AD-related cytokines, such as Th1- (TNF-α and IL-1β and -12) and Th2 (IL-4, -5, -6, -13, and -31)-related cytokines as well as that of cyclooxygenase-2 and CXCL9. Moreover, in the AA treatment group, the protein level of inflammatory cytokines, including COX-2, IL-6, TNF-α, and IL-8, as well as the NF-κB and MAPK signaling pathways, were decreased. Overall, our study confirmed that AA administration inhibited AD skin lesion formation via enhancing immunomodulation and inhibiting inflammation. Thus, AA can be used as palliative medication for regulating AD symptoms.


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