Derma-Hc, a New Developed Herbal Formula, Ameliorates Cutaneous Lichenification in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic cutaneous disorder that is characterized by severe eczematous inflammation, swelling, and lichenification. Activation of T helper (Th)-22 cells by allergens leads to epidermal hyperplasia with hyperkeratosis at the chronic phase of AD. Derma-Hc is composed of five natural herbs with anti-AD effects, such as Astragalus membranaceus BUNGE, Schizonepeta tenuifolia Briq., Cryptotympana pustulata Fabr., Angelica sinensis Diels, Arctium lappa L. In this study, the ameliorative effect of Derma-Hc on cutaneous lichenification in 2,4-dinitrochlorobenzne (DNCB)-induced AD was investigated. The dorsal skin of mice was sensitized with DNCB to induce AD-like skin lesions. The dermatitis score and frequency of scratching were evaluated. Thickness of epidermis and dermis was measured by staining with H&E. In addition, infiltration of the mast cell was observed by staining with toluidine blue. Then, desmosomal cadherin, DSC1 was examined by immunofluorescence. Pathological mechanisms involved in lichenification were analyzed in AD-like skin lesions and TNF-α + IFN-γ-treated with human keratinocytes including keratinocyte differentiation genes and JAK1-STAT3 signaling pathway with IL-22 by RT-PCR and western blotting. Topical treatment of Derma-Hc improved AD-like symptoms such as dryness, edema and lichenefication and decreased the number of scratches. Histopathological analysis demonstrated that Derma-Hc significantly inhibited epidermal hyperplasia, hyperkeratosis, and mast cells infiltration. In addition, the level of DSC1 was highly expressed in the epidermis by Derma-Hc. Moreover, mRNA expression level of FLG, an epidermal differentiation complex gene, was recovered by Derma-Hc treatment. KLK5 and KLK7 were markedly reduced to normalize keratinocyte differentiation in dorsal skin tissues and human keratinocytes. On the other hand, Derma-Hc restored expression level of SPINK5. In addition, Derma-Hc inhibited IL-22 via the blockade of JAK1-STAT3 signal pathway. Taken together, Derma-Hc, a natural herbal formula, regulated keratinocyte differentiation and inhibited epidermal hyperplasia with hyperkeratosis. Therefore, Derma-Hc could be a promising candidate for treating chronic AD through modulating signaling of IL-22-associated skin lichenification.

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Therapeutic Effects of Chinese Herbal Formula (PTQX) on NC/Nga Mice with Atopic Dermatitis-Like Skin Lesions

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/8359252 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13

Author(s):

Fenggen Yan ◽

Jing Zhang ◽

Xiong Li ◽

Xiumei Mo ◽

Junfeng Liu ◽

...

Keyword(s):

Atopic Dermatitis ◽

Mast Cells ◽

Lymph Nodes ◽

Immunoglobulin E ◽

Skin Lesions ◽

Therapeutic Effects ◽

Herbal Formula ◽

Dorsal Skin ◽

Chinese Herbal Formula ◽

Chinese Herbal

Atopic dermatitis (AD), also known as atopic eczema, is a chronic pruritic inflammatory skin disease. The available systemic therapies for atopic dermatitis are inadequate. Objective. This study aimed to evaluate the effects of the Chinese herbal formula Pei Tu Qing Xin (PTQX) on dermatitis severity and ear swelling, immunomodulation, and the infiltration of mast cells in a mouse model of 1-chloro-2,4-dinitrobenzene- (DNCB-) induced AD. Methods. AD-like symptoms were induced by DNCB in NC/Nga mice. Skin lesions, dermatitis, ear swelling, and scratching behaviour were evaluated. Changes in the T-helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) subtypes and immunoregulation in the spleen and lymph nodes were detected by flow cytometry. Results. Histopathological and immunohistochemical analyses demonstrated that PTQX decreased the DNCB-mediated induction of mast cells and infiltration of inflammatory cells in the ear and dorsal skin. PTQX also reduced the DNCB-induced increase in the serum immunoglobulin E level, pruritus, and dermatitis (red, flaky areas) on the dorsal skin. Furthermore, PTQX regulated the balance between the populations of Th1, Th2, Th17, and Treg cells (particularly the latter two) in the lymph nodes. Conclusions. Our results suggest that the Chinese herbal formula PTQX can alleviate symptoms of AD, such as epithelial damage, redness, swelling, and pruritus, and potentially be used to treat this condition.

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Salvia plebeia Suppresses Atopic Dermatitis-Like Skin Lesions

The American Journal of Chinese Medicine ◽

10.1142/s0192415x1450061x ◽

2014 ◽

Vol 42 (04) ◽

pp. 967-985 ◽

Cited By ~ 29

Author(s):

Jin Kyeong Choi ◽

Hyun-Mee Oh ◽

Soyoung Lee ◽

Taeg Kyu Kwon ◽

Tae-Yong Shin ◽

...

Keyword(s):

Atopic Dermatitis ◽

Inflammatory Diseases ◽

Human Keratinocytes ◽

Nuclear Factor Κb ◽

Skin Lesions ◽

Mechanisms Of Action ◽

Histopathological Analysis ◽

Cytokines And Chemokines ◽

Mitogen Activated Protein ◽

Underlying Mechanisms

Salvia plebeia R. Br. (Lamiaceae) has been used for folk medicines in Asian countries, including Korea and China, to treat skin inflammatory diseases and asthma. In this study, we investigated the effects of S. plebeia extract (SPE) on atopic dermatitis (AD)-like skin lesions and defined underlying mechanisms of action. We established an AD model in BALB/c mice by repeated local exposure of house dust mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) to the ears. Repeated alternative treatment of DFE/DNCB caused AD-like skin lesions. The oral administration of SPE decreased AD symptoms based on ear thickness and histopathological analysis, in addition to serum IgE and IgG2a levels. SPE suppressed mast cell infiltration into the ear and serum histamine level. SPE inhibited Th1/Th2/Th17 phenotype CD4+ T lymphocytes expansion in the lymph node and the expression of Th1/Th2/Th17 cytokines in the ear tissue. To define the underlying mechanisms of action, the tumor necrosis factor (TNF)-α and interferon (IFN)-γ activated human keratinocytes (HaCaT) model was used. SPE significantly suppressed the expression of cytokines and chemokines through the down-regulation of mitogen-activated protein kinases, nuclear factor-κB, and STAT1 in HaCaT cells. Taken together, our results suggest that SPE might be a candidate for the treatment of AD.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22052334 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2334

Author(s):

Jae Ho Choi ◽

Gi Ho Lee ◽

Sun Woo Jin ◽

Ji Yeon Kim ◽

Yong Pil Hwang ◽

...

Keyword(s):

Atopic Dermatitis ◽

Skin Lesions ◽

Histopathological Analysis ◽

Mrna Levels ◽

Chemokine Production ◽

Dermal Thickness ◽

Skin Symptoms ◽

Tnf Α ◽

Ifn Γ ◽

In Cells

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.

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Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality

Nutrients ◽

10.3390/nu12123638 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3638

Author(s):

Yoon-Young Sung ◽

Heung-Joo Yuk ◽

Won-Kyung Yang ◽

Seung-Hyung Kim ◽

Dong-Seon Kim

Keyword(s):

Atopic Dermatitis ◽

Immunoglobulin E ◽

Allergic Inflammation ◽

Skin Barrier ◽

Human Keratinocytes ◽

Skin Lesions ◽

Protein Levels ◽

Siraitia Grosvenorii ◽

Ifn Γ

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.

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Triticum�aestivum sprout extract attenuates 2,4‑dinitrochlorobenzene‑induced atopic dermatitis‑like skin lesions in mice and the expression of chemokines in human keratinocytes

Molecular Medicine Reports ◽

10.3892/mmr.2018.9339 ◽

2018 ◽

Cited By ~ 4

Author(s):

Ji‑Hyun Lee ◽

Hyeon‑Hui Ki ◽

Dae‑Ki Kim ◽

Young‑Mi Lee

Keyword(s):

Triticum Aestivum ◽

Atopic Dermatitis ◽

Human Keratinocytes ◽

Skin Lesions

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The Suppressive Effect of Leucine-Rich Glioma Inactivated 3 (LGI3) Peptide on Impaired Skin Barrier Function in a Murine Model Atopic Dermatitis

Pharmaceutics ◽

10.3390/pharmaceutics12080750 ◽

2020 ◽

Vol 12 (8) ◽

pp. 750

Author(s):

Ui Seok Kim ◽

Jin Woo Park ◽

Eon Sub Park ◽

Joon Seok Bang ◽

Tae Woo Jung ◽

...

Keyword(s):

Atopic Dermatitis ◽

Murine Model ◽

Barrier Function ◽

Skin Barrier ◽

Clinical Score ◽

Skin Lesions ◽

Suppressive Effect ◽

Skin Barrier Function ◽

Skin Thickness ◽

Dorsal Skin

This study aimed to restore the skin barrier function from atopic dermatitis (AD) via treatment with leucine-rich glioma inactivated 3 (LGI3) peptide. Male NC/Nga mice (7 weeks, 20 g) were randomly allocated into three groups (control, AD, and LGI3 group). After induction of AD skin lesions with Dermatophagoides farinae ointment, mice were treated with LGI3. The clinical score of AD was the highest and the dorsal skin thickness was the thickest in the AD group. In contrast, LGI3 treatment improved the clinical score and the dorsal skin thickness compared to the AD model. LGI3 treatment suppressed histopathological thickness of the epithelial cell layer of the dorsal skin. LGI3 treatment could indirectly reduce mast cell infiltration through restoring the barrier function of the skin. Additionally, the filaggrin expression was increased in immunohistochemical evaluation. In conclusion, the ameliorating effect and maintaining skin barrier homeostasis in the AD murine model treated with LGI3 could be attributed to complete re-epithelialization of keratinocytes. Hence, LGI3 might be considered as a new potential therapeutic target for restoring skin barrier function in AD.

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Effect of Lactobacillus strains on thymus and chemokine expression in keratinocytes and development of atopic dermatitis-like symptoms

Beneficial Microbes ◽

10.3920/bm2017.0162 ◽

2018 ◽

Vol 9 (4) ◽

pp. 643-652 ◽

Cited By ~ 1

Author(s):

T. Kawahara ◽

N. Hanzawa ◽

M. Sugiyama

Keyword(s):

Atopic Dermatitis ◽

Lactobacillus Reuteri ◽

Human Keratinocytes ◽

Skin Lesions ◽

Suppressive Effect ◽

Water Soluble ◽

Beneficial Effects ◽

Tnf Α ◽

Atopic Skin ◽

Water Soluble Extract

Lactobacillus strains, a major group of lactic acid bacteria, are representative food microorganisms that have many potential beneficial effects via their interactions with immune and intestinal epithelial cells. However, little is known about the effect of Lactobacillus strains on atopic dermatitis via keratinocytes, which comprise the physical barrier of the skin. In this study, we report that Lactobacillus strains have a significant suppressive effect on tumour necrosis factor (TNF)-α-induced expression and production of thymus and activation-regulated chemokine (TARC), a T helper 2 cell chemokine responsible for atopic dermatitis, in human keratinocytes. An RNA interference study showed that the effect of Lactobacillus reuteri strain Japan Collection of Microorganisms (JCM) 1112, the most suppressive strain, depended on the presence of Toll-like receptor 2 and the induction of A20 (also known as TNF-α-induced protein 3) and cylindromatosis in HaCaT cells. Topical application of a water-soluble extract of homogenised JCM 1112 cells significantly suppressed the development of house dust mite-induced atopic skin lesions and TARC expression at the lesion sites in NC/Nga mice. Our study provides new insights into the use of Lactobacillus strains as suppressive agents against keratinocyte-involved atopic inflammation of the skin.

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Effect of Resveratrol-Enriched Rice on Skin Inflammation and Pruritus in the NC/Nga Mouse Model of Atopic Dermatitis

International Journal of Molecular Sciences ◽

10.3390/ijms20061428 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1428 ◽

Cited By ~ 5

Author(s):

Min Kang ◽

Kyohee Cho ◽

Jae Lee ◽

Lalita Subedi ◽

Silvia Yumnam ◽

...

Keyword(s):

Atopic Dermatitis ◽

Immunoglobulin E ◽

Alternative Therapy ◽

Human Keratinocytes ◽

Skin Inflammation ◽

Skin Lesions ◽

Enzyme Linked Immunosorbent Assay ◽

Skin Model ◽

3D Skin

Resveratrol-enriched rice (RR) was developed using genetic engineering to combine the properties of resveratrol and rice. To evaluate the effect of RR on pruritic skin inflammation in atopic dermatitis (AD)-like skin lesions, we used dinitrochlorobenzene (DNCB)-induced NC/Nga mice and an in vitro 3D skin model. Normal rice (NR), resveratrol, and RR were topically applied to mice dorsal skin, following which the dermatitis index and scratching frequency were calculated. Histological examination was performed by hematoxylin and eosin and immunohistochemistry staining of IL-31 level. The level of immunoglobulin E (IgE) and IL-31 in the serum was determined by enzyme-linked immunosorbent assay (ELISA). The cytotoxicity of RR and the expression levels of pro-inflammatory cytokines were also determined in cultured human keratinocytes and a 3D skin model. RR significantly reduced scratching frequency, decreased the dermatitis severity and trans-epidermal water loss (TEWL) and improved skin hydration in DNCB-induced NC/Nga mice. RR also significantly decreased serum IL-31 and IgE levels and suppressed the production of IL-6 in human keratinocytes and the 3D skin model. Our study indicates that the synergistic effect of rice and resveratrol manifested by the topical application of RR can serve as a potential alternative therapy for chronic skin inflammatory diseases such as AD.

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