Regulatory effects of chrysophanol, a bioactive compound of AST2017-01 in a mouse model of 2,4-dinitrofluorobenzene-induced atopic dermatitis.

The aim of this study is to determine whether AST2017-01 which consists of Rumex crispus and Cordyceps militaris would improve atopic dermatitis (AD). We analyzed anti-AD effects of AST2017-01 and chrysophanol, a bioactive compound of AST2017-01, using a 2,4-dinitrofluorobenzene-induced AD murine model. AST2017-01 and chrysophanol relieved clinical severity in AD-like skin lesions and significantly decreased scratching behavior. The thickness of epidermis and infiltration of inflammatory cells in AD-like skin lesions were reduced by AST2017-01 or chrysophanol. AST2017-01 and chrysophanol significantly suppressed the levels of histamine, immunoglobulin E, thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-6, and tumor necrosis factor-α in serum of AD mice. The protein levels of TSLP, intercellular adhesion molecule-1, and macrophage inflammatory protein 2 were significantly inhibited in the skin lesions. The mRNA expressions of TSLP, thymus and activation-regulated chemokine/CCL17, and C-C chemokine receptor 3 were inhibited in the skin lesions by AST2017-01 or chrysophanol. In addition, AST2017-01 and chrysophanol significantly suppressed the expressions and activities of caspase-1 in the skin lesions. Taken together, these results suggest that AST2017-01 has beneficial effects on AD and may be used as a health functional food in AD.

Anticancer agent ABT-737 possesses anti-atopic dermatitis activity via blockade of caspase-1 in atopic dermatitis in vitro and in vivo models.

OBJECTIVE: Previous studies reported that depletion of Bcl-2 has a protective effect against allergic diseases. Furthermore, recently our study showed that anticancer drug has antiallergic inflammatory effect. An anticancer agent ABT-737 is an inhibitor of Bcl-2 and has an anti-inflammatory effect. However, the antiallergic inflammatory activity of ABT-737 is still unknown. Here, we aimed to explore the anti-atopic dermatitis (AD) activity and the mechanism of ABT-737 in AD models. MATERIALS AND METHODS: HaCaT cells were used for in vitro experiments. To evaluate the effect of ABT-737 in vivo model, BalB/c mice were orally administered ABT-737 for 6 weeks in 2,4-dinitrofluorobenzene (DNFB)-induced AD-like murine model. Major assays were enzyme-linked immunosorbent assay, reverse transcription-PCR, caspase-1 assay, histamine assay, and H&E staining. RESULTS: ABT-737 significantly decreased thymic stromal lymphopoietin (TSLP) secretion and caspase-1 activity in activated HaCaT cells. In DNFB-induced AD mice, oral administration of ABT-737 alleviated clinical severity and scratching behavior. ABT-737 decreased levels of AD-related biomarkers including IgE, histamine, TSLP, and inflammatory cytokines. In addition, ABT significantly reduced caspase-1 activity in skin lesions of AD mice. DISCUSSION AND CONCLUSIONS: ABT-737 elicited an anti-AD activity via suppression of caspase-1 activation in AD in vitro and in vivo models. Therefore, this study provides important information regarding the use of anticancer drugs for controlling allergic inflammatory diseases.

Inhibitory effect of naringenin via IL-13 level regulation on thymic stromal lymphopoietin-induced inflammatory reactions.

Naringenin (NG) has various beneficial properties, such as anti-cancer and anti-inflammatory effects. Thymic stromal lymphopoietin (TSLP) induces mast cell proliferation and inflammatory reactions. The aim of this study was to investigate the regulatory effect of NG on TSLP-induced mast cell proliferation and inflammatory reactions using human mast cell line (HMC-1) cells. HMC-1 cells were pre-treated with NG and then treated with TSLP. HMC-1 cells proliferation was determined by quantifying bromodeoxyuridine incorporation. Levels of anti-apoptotic and pro-apoptotic factors were analyzed by western blot analysis. The productions and mRNA expressions of interleukin (IL)-13 and tumour necrosis factor-α (TNF-α) were analyzed by ELISA and quantitative real-time PCR. We found that NG significantly attenuated HMC-1 cells proliferation and Ki-67 mRNA expression promoted by TSLP. NG significantly suppressed mRNA expression of TSLP receptor and IL-7 receptor α in TSLP-treated HMC-1 cells. NG significantly down-regulated levels of phosphorylated-signal transducer and activation of transcription 6 and murine double-minute 2 in TSLP-treated HMC-1 cells, up-regulated levels of cleaved poly ADP-ribose polymerase and p53 in TSLP-treated HMC-1 cells. Furthermore, NG significantly decreased the productions and mRNA expressions of IL-13 and TNF-α in TSLP-treated HMC-1 cells. These results suggest NG has an inhibitory effect on mast cell-mediated allergic inflammatory reactions.

ß-eudesmol suppresses allergic reactions via inhibiting mast cell degranulation.

The regulatory effect of ß-eudesmol, which is an active constituent of Pyeongwee-San (KMP6), is evaluated for allergic reactions induced by mast cell degranulation. Phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cell line, HMC-1 cells, and compound 48/80-stimulated rat peritoneal mast cells (RPMCs) are used as the in vitro models; mice models of systemic anaphylaxis, ear swelling, and IgE-dependent passive cutaneous anaphylaxis (PCA) are used as the in vivo allergic models. The results demonstrate that ß-eudesmol suppressed the histamine and tryptase releases from the PMA plus calcium ionophore A23187-stimulated HMC-1 cells. ß-eudesmol inhibits the expression and activity of histidine decarboxylase in the activated HMC-1 cells. In addition, ß-eudesmol inhibits the levels of histamine and tryptase released from the compound 48/80-stimulated RPMCs. Furthermore, ß-eudesmol decreases the intracellular calcium level in the activated RPMCs. ß-eudesmol also decreases the compound 48/80-induced mortality and ear swelling response. ß-eudesmol suppresses the serum levels of histamine, IgE, interleukin (IL)-1ß, IL-4, IL-5, IL-6, IL-13, and vascular endothelial growth factor (VEGF) under PCA mice as well as PCA reactions. Therefore, the results from this study indicate the potential of ß-eudesmol as an anti-allergic drug with respect to its pharmacological properties against mast cell-mediated allergic reactions.

Inhibitory effects of atractylone on mast cell-mediated allergic reactions.

This study investigated a salutary effect of atractylone (Atr) which is an active constituent of Pyeongwee-San (KMP6) on mast cell-mediated allergic reactions. Our previous report indicated that KMP6 regulated allergic reactions. Thus, this study sought to determine the potential of Atr in vitro models, compound 48/80-stimulated rat peritoneal mast cells (RPMCs), phorbol 12-myristate 13-acetate (PMA) plus A23187-stimulated human mast cell line (HMC-1) cells, and stem cell factor (SCF)-stimulated RPMCs as well as in vivo models, IgE-mediated passive cutaneous anaphylaxis (PCA), compound 48/80-induced systemic anaphylaxis, and compound 48/80-induced ear swelling. The results showed that Atr inhibited compound 48/80-induced RPMCs degranulation, intracellular calcium level, tryptase release, and histamine release. Atr inhibited the up-regulation of p56(lck) tyrosine kinase activity by compound 48/80. And Atr reduced tryptase and histamine releases from PMA plus A23187-stimulated HMC-1 cells. In addition, Atr decreased histidine decarboxylase activity and expression in the activated HMC-1 cells. Atr inhibited SCF-induced morphological alteration and filamentous actin formation in RPMCs. Atr improved IgE-induced PCA reaction by decreasing the levels of histamine, IgE, interleukin (IL)-4, IL-5, IL-6, vascular endothelial growth factor, and IL-13 in the serum of PCA-induced mice. Furthermore, Atr mitigated compound 48/80-induced systemic anaphylaxis and ear swelling. Taken together, these results of this study indicate that Atr regulates the degranulation of mast cell, proving its potential in the treatment of mast cell-mediated allergic reactions.

A novel compound 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide downregulates TSLP through blocking of caspase-1/NF-κB pathways.

Thymic stromal lymphopoietin (TSLP) is regarded as the main factor responsible for the pathogenesis of allergic disorders such as atopic dermatitis, chronic obstructive pulmonary diseases, and allergic rhinitis. As part of our continuing search for novel anti-inflammatory compounds, 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide (PA) was analyzed. In the present study, we examined how PA regulates the mRNA expression and production of TSLP in the human mast cell line, HMC-1 cells. Computer-aided docking simulation, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, caspase-1 assay, and Western blotting were used to investigate the effects of PA. PA decreased the mRNA expression and production of TSLP in HMC-1 cells. PA (1µM) inhibited the TSLP production up to 87.710±5.201%. PA also improved the activation and phosphorylation of nuclear factor-κB as well as the degradation and phosphorylation of IκBα. Caspase-1 activation was up-regulated in activated HMC-1 cells, whereas caspase-1 activation was down-regulated by PA. Finally, PA inhibited ear swelling response induced by phorbol myristate acetate in mice. These results indicate that PA would be effective to treat inflammatory and atopic disorders through the down-regulations of TSLP.

Effects of bamboo salt and its component, hydrogen sulfide, on enhancing immunity.

Korean bamboo salt (BS) is known to have therapeutic effects in the treatment of diseases, including viral disease, dental plaque, diabetes, circulatory organ disorders, cancer and inflammatory disorders. However, the effect of BS on immune functions remains to be elucidated. The present study was designed to determine the immune­enhancing effect of BS and its component, hydrogen sulfide, using RAW264.7 macrophages and a forced swimming test (FST) animal model. BS and sodium hydrosulfide (NaSH), a hydrogen sulfide donor, significantly increased the levels of tumor necrosis factor (TNF)­α through the activation of nuclear factor­κB in the RAW 264.7 cells. In an in vivo experiment, BS and NaSH were administered orally once a day for 28 days. After the 28 days, the immobility times in the FST were significantly decreased in the BS and NaSH­fed groups, compared with the control group. In addition, BS and NaSH induced significant increases in the levels of interferon­Î³, interleukin­2 and TNF­α, compared with the control group. Taken together, these results indicated that BS and NaSH may improve immune function.