calcimycin and Dermatitis

Insamhodo-tang (IHT) has traditionally been used in Korea to treat a variety of diseases, including chronic cough, tuberculosis, and chronic bronchitis. However, the anti-allergic and anti-inflammatory effects of IHT and its molecular mechanisms have yet to be clearly elucidated. In this study, we attempted to evaluate the effects of IHT on mast cell-mediated allergy inflammation in vitro and in vivo.. We investigated to ascertain the pharmacological effects of IHT on both compound 48/80-induced and 2,4-dinitrofluorobenzene (DNFB)-induced allergic reactions under in vivo conditions. Additionally, to find a possible explanation for the anti-inflammatory mechanisms of IHT, we evaluated the regulatory effects of IHT on the level of inflammatory mediators in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1).. The finding of this study demonstrated that IHT reduced compound 48/80-induced systemic anaphylactic shock, DNFB-induced dermatitis, and ear swelling responses in mice. Additionally, IHT inhibited the production of interleukin (IL)-6, IL-8, and TNF-α, as well as the activation of nuclear factor-κB and caspase-1 in PMACI-stimulated HMC-1.. Collectively, the findings of this study provide us with a novel insight into the pharmacological actions of IHT as a potential molecule for use in the treatment of allergic inflammation diseases.

Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Calcimycin; Dermatitis; Dinitrofluorobenzene; Edema; Humans; Hypersensitivity; Inflammation; Inflammation Mediators; Ionophores; Male; Mast Cells; Medicine, Korean Traditional; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; p-Methoxy-N-methylphenethylamine; Phytotherapy; Plant Extracts

The aim of the present study was to examine the effects of Avena Rhealba (AR) oatmeal extract on the metabolism of arachidonic acid (AA) and eicosanoids as well as on the expression of cytosolic phospholipase A(2 )(cPLA(2)) in the human keratinocyte cell line HaCaT. For this purpose, we examined the effects of AR on basal and A23187-triggered release of [(3)H]-AA from phospholipids and on the production of [(3)H]-labeled metabolites of the cyclooxygenase (CO) and 5-lipoxygenase (LO) pathways. AR was found to inhibit A23187-triggered [(3)H]-AA mobilization from phospholipids (p<0.05) and production of [(3)H]-labeled metabolites of CO (p<0.05) and LO (p<0.05) pathways. These results suggest AR decreases PLA(2)-dependent mobilization of AA from phospholipids. A closer examination of the effects of AR on prostaglandin 6KF1alpha (6KPGF1alpha), the stable metabolite of prostacyclin, revealed dose-dependent inhibition of this AA metabolite. AR also decreased A23187- and tumor necrosis factor alpha-induced cPLA(2) overexpression, as shown by cPLA(2) immunodetection and mRNA expression. These results demonstrate the high potential of AR in the treatment of inflammatory diseases of the skin.

Topics: Arachidonic Acid; Avena; Calcimycin; Cell Line; Dermatitis; Dose-Response Relationship, Drug; Eicosanoids; Humans; Ionophores; Keratinocytes; Phospholipases A; Plant Extracts

The synthesis, biological evaluation, and structure-activity relationships of a series of 1-(pyridylphenyl)-1-phenyl-2-imidazolylethanols are described. These compounds show potent dose-dependent topical antiinflammatory activity in murine models of skin inflammation. This effect is likely due to inhibition of cytochrome P450 and consequent reduction in levels of 12R-HETE in the skin. These compounds were examined for their ability to inhibit the oxidative metabolism of arachidonic acid; they specifically inhibit the formation of prostacyclins in mouse macrophages. To study the effects of structure on the in vivo activity, three general features of the molecules were varied: the position of attachment of the pyridine nucleus (A), the second aromatic residue (B), and the nitrogen base on the ethanol chain (C). 1-[4-(4-Pyridyl)phenyl]-1-(4-fluorophenyl)-2- imidazolylethanol (2a, DuP 983) shows a very attractive profile of antiinflammatory activity and has been selected for clinical evaluation as a topical antiinflammatory agent.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Arachidonic Acid; Calcimycin; Cyclooxygenase Inhibitors; Dermatitis; Edema; Imidazoles; Lipoxygenase Inhibitors; Male; Mice; Molecular Structure; Phospholipases A; Pyridines; Structure-Activity Relationship; Tetradecanoylphorbol Acetate