Jageum-Jung improves 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice and suppresses pro-inflammatory chemokine production by inhibiting TNF-α/IFN-γ-induced STAT-1 and NFκB signaling in HaCaT cells.

Jageum-Jung (JGJ) is an oriental herbal formula comprising five herbs (Melaphis chinensis Bell, Cremastra variabilis Nakai, Knoxia valerianoides Thorel, Euphorbia lathyris L., and Moschus moschiferus L.). It has been used for detoxification and treating cancer and inflammatory diseases in China, Japan, and Korea. However, the mechanism of action of JGJ on keratinocyte inflammatory response is poorly understood. In the present study, we investigated the anti-inflammatory mechanism of JGJ and studied the effects of JGJ on atopic dermatitis-like skin lesions in mice. We elucidated the anti-inflammatory and anti-inflammatory effects of JGJ on tumor necrosis factor-α/interferon-γ (TNF-α/IFN-γ)-treated human keratinocyte cells, IgE-sensitized RBL-2H3 cells, and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like mice, respectively. The results showed that JGJ suppressed the production and mRNA revels of IL-8, IL-6 and, conspicuously, both TARC and RANTES. JGJ inhibited nuclear translocation of the inflammatory transcription factors NFκB and STAT-1. Moreover, JGJ improved AD-like skin lesions in DNCB-treated mice and inhibited degranulation of mast cell. The results of this study suggest that JGJ can be considered as a candidate agent for AD treatment.

Yang JH ，Do HJ ，Lee E ，Yim NH ，Cho WK ，Park KI ，Ma JY ... -  《-》

Artemisia anomala Herba Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice and the Production of Pro-Inflammatory Mediators in Tumor Necrosis Factor Alpha-/Interferon Gamma-Induced HaCaT Cells.

Yang JH ，Kim KY ，Kim YW ，Park KI ... -  《MOLECULES》

Ethanolic Extracts of Artemisia apiacea Hance Improved Atopic Dermatitis-Like Skin Lesions In Vivo and Suppressed TNF-Alpha/IFN-Gamma⁻Induced Proinflammatory Chemokine Production In Vitro.

Yang JH ，Lee E ，Lee B ，Cho WK ，Ma JY ，Park KI ... -  《Nutrients》

Inhibitory effect of 5,6-dihydroergosteol-glucoside on atopic dermatitis-like skin lesions via suppression of NF-κB and STAT activation.

Atopic dermatitis (AD) is a Th2-type disease. Keratinocytes, a major type in the skin, produce Th2 chemokines such as thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22, which play pivotal roles in the development of Th2-dominant inflammatory skin diseases. Recently, it was reported that 5,6-dihydroergosterol-glucoside (DHE-Glc) was synthesized and exhibited strong anti-inflammatory activity. We aimed to investigate the effects of DHE-Glc, a synthetic molecule derived from ergosterol, on AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in mice and to elucidate the effects of DHE-Glc on TNF-α/IFN-γ-induced production of CCL17 and CCL22 in human keratinocytes (HaCaTs) and DNCB induced skin inflammation mice model. Mice were sensitized and challenged on the skin of their backs with DNCB. At 30-60 days after sensitization, mice were treated with cutaneous administration of DHE-Glc by skin smear. HaCaT cells were used to evaluate the effects of DHE-Glc on production of CCL17 and CCL22 and investigate mechanisms of action by RT-PCR, ELISA, Western blot, and reporter assays. Topical administration of DHE-Glc attenuated AD-like skin inflammatory symptoms. DHE-Glc decreased infiltration of epidermal eosinophils and mast cells, and reduced levels of IgE, histamine, and mRNA expression and protein levels of CCL17/CCL22 in the plasma of DNCB-treated animals. In addition, DHE-Glc suppressed TNF-α/IFN-γ-induced expression of the Th2 chemokines CCL17 and CCL22 by inhibiting NF-κB and STAT activation in TNF-α/IFN-γ-induced HaCaT cells. DHE-Glc improved AD-like skin inflammatory symptoms on the backs of DNCB-induced mice, partly by suppressing production of Th2 chemokines, CCL17 and CCL22 in inflamed skin. Therefore, DHE-Glc is a potential therapeutic agent for skin inflammatory diseases such as AD.

Jung M ，Lee TH ，Oh HJ ，Kim H ，Son Y ，Lee EH ，Kim J ... -  《-》

Improvement of atopic dermatitis with topical application of Spirodela polyrhiza.

Spirodela polyrhiza has been used as a traditional remedy for the treatment of urticarial, acute nephritis, inflammation, as well as skin disease. Atopic dermatitis (AD) is characterized hyperplasia of skin lesion and increase of serum immunoglobulin E (IgE) level. In this study, the topical effects of S. polyrhiza (SP) on 2, 4-dinitrochlorobenzene (DNCB)-induced AD mice model were investigated by several experiments. BALB/c mice were randomly divided into five groups as NOR, CON, DEX, SP 1, and SP 100 groups (n=5, respectively). To induce atopic dermatitis-like skin lesions, DNCB had been applied on shaved dorsal skin. SP was topically treated to DNCB-induced mice as 1 and 100mg/mL concentrations. Histological changes were showed by hematoxylin and eosin (H&E) staining and the infiltration of mast cells was detected by toluidine blue staining. In addition, the level of IgE and each cytokines were measured and expressions of inflammatory signaling factors were analyzed by western blotting assay. SP treatment improved a hyperplasia of epidermis and dermis in DNCB-induced AD-like skin lesion. The infiltration of mast cells was also decreased by treatment of SP. In addition, SP reduced the level of IgE in serum and attenuated the secretion of cytokines such as interleukin (IL)-4, IL-6, and tumor necrosis factor (TNF)-α. Treatment of SP also inhibited the expressions of pro-inflammatory mediators including nuclear factor-κB (NF-κB), phosphor-IκB-α, and mitogen-activated protein kinase (MAPK)s. From these data, we propose that SP ameliorates AD via modulation of pro-inflammatory mediators. SP may have the potential to be used as an alternative for treatment of AD.

Lee HJ ，Kim MH ，Choi YY ，Kim EH ，Hong J ，Kim K ，Yang WM ... -  《-》