Dictamnine Ameliorates DNFB-Induced Atopic Dermatitis Like Skin Lesions in Mice by Inhibiting M1 Macrophage Polarization and Promoting Autophagy.

Autophagy and M1 macrophage polarization play important roles in the regulation of inflammation in atopic dermatitis (AD). Dictamnine is one of the main ingredients in Cortex Dictamni, a widely used traditional Chinese medicine for the treatment of dermatitis. In the present study, we investigated the anti-inflammatory effects of dictamnine on AD like skin lesions and M1 macrophage polarization. A 2,4-dinitrofluorobenzene (DNFB) triggered AD like skin lesions models in mice was established to identify the ameliorative effects of dictamnine on AD in vivo. In addition, an M1 macrophage polarization model was co-stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) using phorbol myristate acetate (PMA) differentiated THP-1 cells, to investigate the effect of dictamnine on promoting autophagy and inhibiting inflammatory factor release. Dictamnine suppressed DNFB-induced skin inflammation by inhibiting M1 macrophage polarization, up-regulating the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3) expression, and promoting macrophage autophagy at inflammatory sites. Dictamnine also could reduce the release of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8), and down-regulate the mRNA expression of these genes in LPS-IFN-γ triggered M1 polarized macrophages. Dictamnine ameliorates AD like skin lesions by inhibiting M1 macrophage polarization and promoting autophagy. Hence, dictamnine is expected to be a potential therapeutic candidate for AD.

Alpha-linolenic acid improves nasal mucosa epithelial barrier function in allergic rhinitis by arresting CD4+ T cell differentiation via IL-4Rα-JAK2-STAT3 pathway.

BACKGROUND: Allergic rhinitis (AR) defined as inflammation and tissue remodeling of the nasal mucosa in atopic individuals after allergen exposure. Alpha-linolenic acid [cis-9, cis-12, cis-15-octadecatrienoic acid (18:3)] (ALA) as dietary supplementation can reduce inflammation and allergic symptoms. OBJECTIVE: To evaluate the potential therapeutic effect and mechanism of ALA in AR mouse model. METHODS: Ovalbumin sensitized AR mouse model were challenged with oral ALA administration. Nasal symptoms, tissue pathology, immune cell infiltration and goblet cell hyperplasia were investigated. Levels of IgE, TNF-ß, IFN-γ, IL-2, IL-4, IL-5, IL-12, IL-13 and IL-25 were determined by ELISA in serum and nasal fluid. Quantitative RT-PCR and immunofluorescence were performed for occludin and zonula occludens-1 expression. CD3+CD4+ T-cells from peripheral blood and splenic lymphocytes were isolated and Th1/Th2 ratio were determined. Mouse naive CD4+ T cell were isolated and Th1/Th2 ratio, IL-4Rα expression, and IL5/IL13 secretion were determined. IL-4Rα-JAK2-STAT3 pathway change in AR mice were performed by western blot. RESULTS: Ovalbumin induced AR, nasal symptoms, pathological performance, IgE, and cytokine production. ALA treated mice showed reduced nasal symptoms, nasal inflammation, nasal septum thickening, goblet cell hyperplasia, and eosinophil infiltration. In serum and nasal fluid of ovalbumin challenged mice, ALA decreased IgE, IL-4 levels, and the increase of Th2-cells. ALA prevented the disruption of the epithelial cell barrier in ovalbumin-challenged AR mice. Simultaneously, ALA prevents IL-4 induced barrier disruption. ALA treatment of AR by affecting the differentiation stage of CD4+T cells and block IL-4Rα-JAK2-STAT3 pathway. CONCLUSION: This study suggests that ALA has the potential therapeutic effect to ovalbumin-induced AR. ALA can affect the differentiation stage of CD4+T cells and improve epithelial barrier functions through IL-4Rα-JAK2-STAT3 pathways. CLINICAL IMPLICATION: ALA might be considered as drug candidate for improving epithelial barrier function through Th1/Th2 ratio recovery in AR.

Silibinin attenuated pseudo-allergic reactions and mast cell degranulation via PLCγ and PI3K/Akt signaling pathway.

Anaphylaxis is a type of potentially fatal hypersensitivity reaction resulting from the activation of mast cells. Many endogenous or exogenous factors could cause this reaction. Silibinin is the main chemical component of silymarin and has been reported to have pharmacological activities. However, the anti-allergic reaction effect of silibinin has not yet been investigated. This study aimed to evaluate the effect of silibinin to attenuate pseudo-allergic reactions in vivo and to investigate the underlying mechanism in vitro. In this study, calcium imaging was used to assess Ca2+ mobilization. The levels of cytokines and chemokines, released by stimulated mast cells, were measured using enzyme immunoassay kits. The activity of silibinin was evaluated in a mouse model of passive cutaneous anaphylaxis (PCA). Western blotting was used to explore the related molecular signaling pathways. In results, silibinin markedly inhibited mast cell degranulation, calcium mobilization, and preventing the release of cytokines and chemokines in a dose-dependent manner via the PLCγ and PI3K/Akt signaling pathway. Silibinin also attenuated PCA in a dose-dependent manner. In summary, silibinin has an anti-pseudo-allergic pharmacological activity, which makes it a potential candidate for the development of a novel agent to arrest pseudo-allergic reactions.