Use of Physcion to Improve Atopic Dermatitis-Like Skin Lesions through Blocking of Thymic Stromal Lymphopoietin.

Physcion is well known for the treatment of carcinoma. However, the therapeutic effect of physcion on atopic dermatitis (AD) through the inhibition of thymic stromal lymphopoietin (TSLP) level remains largely unknown. In this study, we investigated the anti-AD effect of physcion using HMC-1 cells, splenocytes, and a murine model. Treatment with physcion decreased production and mRNA expression levels of TSLP, IL-6, TNF-ɑ, and IL-1ß in activated HMC-1 cells. Physcion reduced the expression levels of RIP2/caspase-1 and phospho (p)ERK/pJNK/pp38 in activated HMC-1 cells. Physcion suppressed the expression levels of pIKKß/NF-κB/pIkB in activated HMC-1 cells. Moreover, physcion attenuated the production levels of TSLP, IL-4, IL-6, TNF-, and IFN-γ from activated splenocytes. Oral administration of physcion improved the severity of 2,4-dinitrochlorobenzene-induced AD-like lesional skin through reducing infiltration of inflammatory cells and mast cells, and the protein and mRNA levels of TSLP, IL-4, and IL-6 in the lesional skin tissues. Physcion attenuated histamine, IgE, TSLP, IL-4, IL-6, and TNF- levels in serum. In addition, physcion inhibited caspase-1 activation in the lesional skin tissues. These findings indicate that physcion could ameliorate AD-like skin lesions by inhibiting TSLP levels via caspase-1/MAPKs/NF-kB signalings, which would provide experimental evidence of the therapeutic potential of physcion for AD.

ß-eudesmol inhibits thymic stromal lymphopoietin through blockade of caspase-1/NF-κB signal cascade in allergic rhinitis murine model.

Allergic rhinitis (AR) is a global health problem because of its steadily increasing incidence and prevalence that currently affects about 30% of people worldwide. ß-eudesmol has various beneficial effects, including anti-cancer and anti-allergic activities. However, the effects of ß-eudesmol on AR have not yet been clarified; thus, we investigated the effects of ß-eudesmol in an ovalbumin-induced AR animal model using enzyme-linked immunosorbent assay, histamine assay, Western blotting, and hematoxylin and eosin staining methods. ß-eudesmol reduced the nasal rubs score and levels of histamine and immunoglobulin E in serum of AR mouse. In addition, the levels of thymic stromal lymphopoietin, interleukin-1ß, tumor necrosis factor-α, and macrophage inflammatory protein-2 were down-regulated and infiltration of eosinophils and the level of intercellular adhesion molecule-1 were inhibited by ß-eudesmol administration. ß-eudesmol administration also reduced active caspase-1 and nuclear factor-κB DNA binding activity in nasal mucosa tissues of AR mice. Taken together, these results indicate that ß-eudesmol would be effective for the treatment of allergic and inflammatory diseases, such as AR.

Improvement effects of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich on postmenopausal symptoms of ovariectomized mice.

BACKGROUND: Menopausal hot flushes occur frequently in postmenopausal women. In the present study, we investigated a regulatory effect of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich (PCE17), an extract of flowers of Pueraria thomsonii Benth. (PE), an extract of peels of Citrus unshiu Markovich (CE), a mixture of tectorigenin 7-O-xylosylglucoside, tectoridin, and tectorigenin (Tec, the active compounds of PE), and hesperidin (Hes, an active compound of CE) on menopausal hot flushes. METHODS: We examined the anti-hot flushes properties of PCE17, PE, CE, Tec, or Hes using a mouse model of ovariectomy-induced hot flushes. RESULTS: The ovariectomy-induced rise in the tail skin temperature was significantly prevented by PCE17, PE, CE, Tec, or Hes. PCE17, PE, CE, Tec, or Hes significantly enhanced 5-HT levels and attenuated RANKL levels in the hypothalamus of ovariectomized (OVX) mice. Treatment with PCE17, PE, CE, Tec, or Hes significantly enhanced the levels of estrogen receptor (ER)-ß, 5-HT1A, 5-HT2A, and tryptophan hydroxylase mRNA expression in the hypothalamus of OVX mice. PCE17, PE, or CE decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, but did not increase estrogen levels in the serum of OVX mice. Tec or Hes decreased FSH or LH levels and increased estrogen levels. Treatment with PCE17, PE, CE, or Tec ameliorated vaginal atrophy in OVX mice. Finally, PCE17, PE, CE, Tec, or Hes significantly increased norepinephrine and dopamine levels in the hypothalamus of OVX mice. CONCLUSION: Thus, these results imply that PCE17 has protective effects against hot flushes.

Protective effects of rutin through regulation of vascular endothelial growth factor in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is an allergic inflammatory disease induced by various mediators released by infiltrating inflammatory cells. Vascular endothelial growth factor (VEGF) increases the airway inflammatory response by promoting vascular permeability. Furthermore, it is known that Allium hookeri and one of its constituent compounds, rutin (RU), have anti-inflammatory, antioxidant, and antiplatelet effects. OBJECTIVE: The aim of this study was to evaluate the regulation of AR by RU and A. hookeri. METHODS: We assessed the therapeutic effects and the regulatory mechanisms of A. hookeri and RU on phorbol 12-myristate 13-acetate plus A23187 (PMACI) stimulated human mast cell line (HMC) 1 cells, and ovalbumin (OVA) sensitized mouse model of AR. RESULTS: A. hookeri and RU significantly inhibited the production and messenger RNA (mRNA) expression of VEGF in PMACI-stimulated HMC-1 cells and significantly decreased VEGF levels in our murine AR model. The increased rubs scores and immunoglobulin E and interleukin (IL) 4 levels in OVA-sensitized mice were significantly reduced by the administration of A. hookeri, and RU significantly inhibited the production and mRNA expression and RU. Also, A. hookeri and RU significantly reduced IL-4 and IL-5 production in OVA-stimulated splenocytes. Furthermore, A. hookeri and RU significantly decreased chemokine levels (intercellular adhesion molecule-1, macrophage inflammatory protein-2) in nasal mucosa tissues. In the mouse AR model, A. hookeri and RU significantly prevented eosinophil and mast cell infiltration and reduced inflammatory cytokine levels induced by OVA sensitization. In addition, A. hookeri and RU significantly reduced mast cell-derived caspase-1 activity in OVA-sensitized mice. CONCLUSION: The present study showed that A. hookeri or RU had an anti-allergic inflammatory effects. Analysis of these results indicated that A. hookeri and RU might protect against AR.