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• Hispidulin ameliorated psoriatic symptoms including scaling, erythema and thickness. • Hispidulin decreased psoriasis associated cytokines and chemokines. • Hispidulin reduced Th1/Th17 cell population in spleen. • Hispidulin inhibited phosphorylation of MAPKs in keratinocytes. Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of epidermal keratinocytes accompanied by increased infiltration of immune cells. Previous studies have demonstrated that hispidulin (4′,5,7-trihydroxy-6-methoxyflavone, HPD) has various pharmacological benefits such as anti-fungal, anti-inflammation, and anti-allergic effects. This study investigated the effectiveness of HPD to treat psoriasis using an imiquimod (IMQ)-induced mouse model and activated keratinocytes. IMQ was topically applied to the back skin of mice for six consecutive days, and the mice were orally administered HPD. Based on the histological observation and immunological analysis, oral administration of HPD suppressed psoriatic characteristics including skin thickness, psoriasis area severity index, transepidermal water loss, and neutrophil infiltration. HPD alleviated pathologically increased levels of immunoglobulin G2a, myeloperoxidase, and tumor necrosis factor-α. Splenic Th1 and Th17 cell populations were also reduced by HPD in the murine model. In addition, in activated keratinocytes, HPD inhibited gene expression of Th1- and Th17-associated cytokines and chemokines, and phosphorylation of mitogen-activated protein kinases and nuclear factor-κB. In summary, HPD alleviates psoriasis skin inflammation in vivo and in vitro. Therefore, we suggest that HPD would be a potent therapeutic candidate for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

• Dabrafenib inhibited IgE-induced mast cell activation. • Dabrafenib decreased the activity of signaling molecules (Lyn, Syk, Akt, and PLCγ). • Dabrafenib reduced IL-4 and TNF-α by the inhibition of NF-κB and NFAT. • Dabrafenib ameliorated mast cell-mediated local anaphylaxis. The functional inhibition of mast cells, which serve as a key effector cells in allergic reactions may be a specific target for treating immunoglobulin (Ig)E-mediated allergic reactions, which occur in various allergic diseases including anaphylaxis, asthma, and atopic dermatitis. In this study, we demonstrated the effects of dabrafenib, a therapeutic agent used to treat metastatic melanoma, with a focus on mast cell activation and local cutaneous anaphylaxis. In two types of mast cells (RBL-2H3 and mouse bone marrow-derived mast cells), dabrafenib (0.01, 0.1, 1 μM) pretreatment significantly decreased IgE-induced degranulation, intracellular calcium influx, and the activity of intracellular signaling molecules, such as Lyn, Syk, Akt, and PLCγ. Dabrafenib ameliorated mRNA and protein expression levels of interleukin-4 and tumor necrosis factor-α by the reduction of nuclear localization of nuclear factor-κB and nuclear factor of activated T-cells. In passive cutaneous anaphylaxis, oral administration of dabrafenib (0.1, 1, 10 mg/kg) reduced local pigmentation and ear thickness in a dose-dependent manner. Taken together, these results suggest that dabrafenib is a therapeutic drug candidate that controls IgE-mediated allergic inflammatory diseases through suppression of mast cell activity. [ABSTRACT FROM AUTHOR]

• UA inhibited mast cell degranulation by reducing intracellular calcium level. • UA attenuated secretion of pro-inflammatory cytokines in mast cells. • These effects of UA were dependent on inhibition of FcεRI-mediated signaling. • UA suppressed the local and systemic anaphylactic reactions. • UA might be a potential candidate for the treatment of allergic diseases. Mast cells are the primary cells that play a crucial role in the allergic diseases via secretion of diverse allergic mediators. Ursolic acid (UA) is a naturally occurring anti-inflammatory triterpenoid possessing various biological properties such as immune regulation, antioxidant, and anti-fibrotic. The aim of this study was to evaluate the effects of UA in FcεRI-mediated mast cell activation and allergic inflammation. In this study, mast cells were stimulated with immunoglobulin E (IgE) and the anti-allergic effects of UA were assessed by measuring the levels of allergic mediators. In vivo effects of UA were observed by generating passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mouse model. We found that UA inhibited the degranulation of mast cell by suppressing the intracellular calcium level in a concentration-dependent manner. UA inhibited the expression and the release of pro-inflammatory cytokines in mast cells. Anti-allergic effects of UA were demonstrated via suppression of FcεRI-mediated signaling molecules. In addition, UA inhibited the IgE-mediated PCA and ovalbumin-induced ASA reactions in a dose-dependent manner. Based on these findings, we suggest that UA might have potential as a therapeutic candidate for the treatment of allergic inflammatory diseases via inhibition of FcεRI-mediated mast cell activation. [ABSTRACT FROM AUTHOR]

Ursolic acid (UA), a pentacyclic triterpenoid, is a common natural substance known to be effective in the treatment of inflammation, oxidative stress, and ulcers in arthritis. This study examined the effects of ursolic acid-3-acetate (UAA), a derivative of UA, on rheumatoid arthritis (RA) and verified the underlying mechanism of action by using a type-II collagen-induced arthritis (CIA) mice model and tumor necrosis factor (TNF)-α-stimulated RA synovial fibroblasts. The oral administration of UAA showed a decrease in clinical arthritis symptoms, paw thickness, histologic and radiologic changes, and serum IgG1 and IgG2a levels. UAA administration reduced Th1/Th17 phenotype CD4 + T lymphocyte expansion and inflammatory cytokine production in draining lymph nodes. In addition, UAA effectively reduced the expression and production of inflammatory mediators, including cytokines and matrix metalloproteinase-1/3 in the knee joint tissue and RA synovial fibroblasts, through the downregulation of IKKα/β, ΙκBα, and nuclear factor-κB. Our findings showed that UAA modulated helper T cell immune responses and matrix-degrading enzymes. The effects of UAA were comparable with those of the positive control drug, dexamethasone. In summary, all the evidence presented in this paper suggest that UAA could be a therapeutic candidate for the treatment of RA. [ABSTRACT FROM AUTHOR]