benzofurans and Dermatitis--Atopic

Topics: Animals; Benzofurans; Cytokines; Depsides; Dermatitis, Atopic; Gene Expression Regulation; Immunoglobulin G; Lithospermum; Male; Mice; Mice, Inbred Strains; Plant Extracts; Skin; Spleen; Th1-Th2 Balance

Atopic dermatitis (AD) is a chronic skin inflammatory disease characterized by uncontrolled Th2 cells response to environmental allergens. Long-term topical application of corticosteroids for treating AD may induce severe side effects. Sulfuretin is a major flavonoid found in Rhus verniciflua and carries antioxidant and anti-inflammatory properties. Its therapeutic effect on AD has not been characterized. We first studied the cytotoxic and regulatory effects of sulfuretin on differentiated Th2 cells. Next, we evaluated therapeutic effect of sulfuretin on AD-like damages caused by 2,4-dinitrochlorobenzene (DNCB) in a mouse model. Serum IgE level, overall symptomatic score, and cytokine accumulation at the lesions were measured. Lastly, we investigated the regulatory mechanism of sulfuretin on GATA3 pathway in primary mouse CD4

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cells, Cultured; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Flavonoids; GATA3 Transcription Factor; Humans; Interleukin-4; Mice; Mice, Inbred BALB C; Skin; Th2 Cells

We have designed and efficiently synthesized novel 1-phenyl-6-aminouracils by replacing the chroman moiety in CX-659S, a nonsteroidal dermatologic candidate, with dimethyldihydrobenzofuranol to cancel CX-659S asymmetric center. Medicinal chemistry effort culminated in the discovery of 13d bearing a 3-methyl group at the 1-phenyl group as a promising compound. Compound 13d, having good in vitro ADME profile and moderate oral bioavailability in mice, showed potent anti-inflammatory activity against hapten-induced contact hypersensitivity reaction in mice following topical and oral administration. The effects of 13d were equipotent to that of tacrolimus or prednisolone. In addition, compound 13d, having potent hydroxyl radical-scavenging activity, showed more potent suppressive effect on substance P-induced pruritus in mice than oxatomide.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Benzofurans; Cell Line, Tumor; Cell Membrane Permeability; Dermatitis, Atopic; Half-Life; Humans; Mice; Microsomes; Pruritus; Rats; Uracil

Topics: Administration, Topical; Animals; Benzofurans; Biopsy, Needle; Cells, Cultured; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Immunohistochemistry; Keratinocytes; Mice; Mice, Inbred Strains; Random Allocation; Sensitivity and Specificity; Thymic Stromal Lymphopoietin

Previous studies reported that exposure to dioxins was associated with an increased risk of various diseases in general populations.. The aim of this study was to examine the association between levels of dioxins in blood and allergic and other diseases.. We conducted a cross-sectional study on 1,063 men and 1,201 women (aged 15-76 years), who were living throughout Japan and not occupationally exposed to dioxins, during 2002-2010. In fasting blood samples, polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like PCBs (DL-PCBs) were analyzed by isotope dilution high-resolution gas chromatography/mass spectrometry. We obtained information on life style and self-reported history of diseases using a questionnaire. Blood pressure, blood levels of hemoglobin A1c, and serum lipids were also measured. Multiple logistic regression models were used to analyze the association between dioxin levels in blood and various diseases.. Toxic equivalents of PCDDs/PCDFs and total dioxins showed significant inverse dose-response relationships with atopic dermatitis, after adjustments for potential confounders. The highest quartile for total dioxins had an adjusted odds ratio of 0.26 (95 % confidence interval 0.08-0.70) compared to the reference group (first quartile). The odds ratios for hypertension, diabetes mellitus, hyperlipidemia, gout in men, and gynecologic diseases in women significantly increased with increasing toxic equivalents of PCDDs/PCDFs, DL-PCBs, and total dioxins in blood.. The present findings suggest that background exposure to dioxins was associated with reduced risk of atopic dermatitis. The results also support the idea that low-level exposure to dioxins is associated with an increased risk of diabetes, hypertension, and hyperlipidemia.

Topics: Adolescent; Adult; Aged; Benzofurans; Cross-Sectional Studies; Dermatitis, Atopic; Diabetes Mellitus; Environmental Exposure; Female; Humans; Hyperlipidemias; Hypertension; Japan; Life Style; Male; Middle Aged; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Surveys and Questionnaires; Young Adult