oregonin and Dermatitis--Atopic

The diarylheptanoid, oregonin (ORE), which was isolated from the bark of Alnus japonica Steudel that grows natively in Korea, has been known to exert antioxidative, anti-inflammatory, anti-cancer and immune response inhibitory effects. The antioxidative effect of ORE was observed on the superoxide and 1,1-diphenyl-2-picrylhydrazyl radical, as well as on the expression of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-treated RAW264.7 macrophages. The statistically significant inhibitory action of ORE against production of cytokines induced by bacterial products or by interleukin (IL)-1beta, free radicals and nitrogen species, and a corresponding increase in cellular calcium concentration because of ORE were confirmed in bone marrow and spleen dendritic cells that are known to play important functions in the development and advancement of atopic dermatitis (AD). It was thus expected that ORE would exert a beneficial effect in the treatment of AD. A study on the pharmaceutical benefits of ORE against AD has not yet been conducted in vivo. We therefore used an in vivo AD animal model, namely the NC/Nga mice, and by applying ORE onto the animals through skin application as well as intraperitoneal injection, we attempted to evaluate the benefits of ORE in this system. Evaluation of ORE was conducted by following the SCORE method to score the effect, as well as by measuring the Th2 cytokines IL-4, IL-5 and IL-13 levels from serum and lymphocytes, and IgE and eosinophil levels from serum. Additionally, the expression of mRNA and protein levels was estimated using real-time polymerase chain reaction and Western blotting analysis. The following categories of clinical evaluation, Th2 cytokines IL-4, IL-5 and IL-13 values, serum IgE levels, serum eosinophil levels, and mRNA and protein expression levels of iNOS and COX-2, were evaluated from topical application and intraperitoneal injection groups of ORE. The effects of ORE on AD in NC/Nga mice were confirmed as being similar to the positive control group, while a significant difference with the negative control group was observed. The results presented in this report suggest that ORE might be beneficial in the treatment of AD.

Topics: Administration, Topical; Alnus; Animals; Cyclooxygenase 2; Cytokines; Dermatitis, Atopic; Diarylheptanoids; Disease Models, Animal; Female; Immunoglobulin E; Injections, Intraperitoneal; Mice; Mice, Inbred Strains; Nitric Oxide Synthase Type II; Plant Extracts; Reactive Oxygen Species; Treatment Outcome

To develop an external preparation of oregonin (ORG) for the treatment of atopic dermatitis (AD), conventional creams (CC) and elastic liposomes (EL) containing ORG have been formulated and examined for their in vitro skin permeation properties and in vivo therapeutic efficacy assessments. EL, consisting of soybean phosphatidylcholine and Tween 80 (85 : 15 w/w %), were of flexible nanocarriers: they were about 130 nm in size and had a 4-fold greater deformability index than conventional liposomes. In a skin permeation study using a Franz diffusion cell mounted with depilated mouse skin, liposomal systems were superior to cream, revealing greater flux values. Both CC and EL were diversified with the addition of Trans-activating transcriptional activator (Tat) peptide, a sort of cell penetrating peptide, and subjected to in vivo efficacy evaluations in NC/Nga mice with AD-like lesions. On clinical observation for skin severity, rapid and profound improvement was observed in the treatment group with Tat-added liposomes (EL/T), showing a significant difference (p<0.05) versus Tat-added cream. The results indicated that EL/T treatment is effective for normalizing the immune-related responses and alleviating AD, evaluated as changes in the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-4, immunoglobulin E (IgE), and eosinophils in skin or blood.

Topics: Administration, Topical; Alnus; Animals; Dermatitis, Atopic; Dermatologic Agents; Diarylheptanoids; Dosage Forms; Elasticity; Female; Glycine max; Immune System; Liposomes; Male; Mice; Mice, Inbred Strains; Nanostructures; Permeability; Phosphatidylcholines; Phytotherapy; Plant Extracts; Polysorbates; Severity of Illness Index; Skin; Trans-Activators

Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing prevalence and severity of AD have prompted the developments of safer, more effective drugs. Although topical corticosteroids have been used as first line therapy for AD, their potential side effects limit their clinical applications. To investigate the effect of hirsutenone (HIR), a diarylheptanoid compound, on AD-like skin lesions and other factors related to immune response is the aim of this paper Th2-related cytokines (IL-4, IL-5, IL-13), eosinophil, IgE inflammatory factors (COX-2, iNOS) levels were reduced in blood, lymphocytes, and tissue after HIR treatment. These results suggest that HIR might be an effective treatment for AD.

Topics: Administration, Cutaneous; Animals; Catechols; Cyclooxygenase 2; Dermatitis, Atopic; Diarylheptanoids; Disease Models, Animal; Eosinophils; Female; Immunoglobulin E; Injections, Intraperitoneal; Interleukins; Mice; Mice, Inbred Strains; Nitric Oxide Synthase Type II; Skin

Antigen-presenting dendritic cells may play an important role in the pathogenesis of inflammatory skin diseases, including atopic dermatitis. Oregonin is demonstrated to have anti-inflammatory and anti-oxidant effects. The present study was designed to assess the effect of oregonin against stimulated responses in dendritic cells of mouse bone marrow and spleen. Dendritic cells exposed to lipopolysaccharide, lipoteichoic acid and IL-1beta exhibited increase in the production of IL-12 p70 and TNF-alpha, increase in the formation of reactive oxygen species and nitric oxide, and elevation of intracellular Ca2+ levels. Treatment of oregonin attenuated the microbial product- or IL-1beta-stimulated responses in dendritic cells in a dose-dependent manner. Oregonin revealed a significant inhibitory effect on the production of cytokine, the formation of reactive oxygen species and nitric oxide, and the change in intracellular Ca2+ levels in dendritic cells of bone marrow and spleen. The results show that oregonin seems to attenuate the stimulated cell responses, including cytokine production, in dendritic cells exposed to microbial products and IL-1beta. The findings suggest that oregonin may exert an inhibitory effect against the dendritic cell-mediated immune response.

Topics: Animals; Calcium; Cell Separation; Cell Survival; Cells, Cultured; Cytokines; Dendritic Cells; Dermatitis, Atopic; Diarylheptanoids; Female; Fluorescent Dyes; Fura-2; Interleukin-12; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nitrates; Nitrites; Reactive Oxygen Species; Teichoic Acids; Tumor Necrosis Factor-alpha