Mast cells are the principal effector cells involved in the allergic response, through the release of histamine. We investigated the effect of eriodictyol, derived from the painted maple and yerba santa, on mast cell degranulation and on an allergic response in an animal model. We also investigated its effect on the expression of the ceramide kinase (CERK) involved in calcium-dependent degranulation, and on ceramide activation by multiple cytokines. Eriodictyol suppressed the release of beta-hexosaminidase, a marker of degranulation, and the expression of interleukin (IL)-4 mRNA. It inhibited the expression of CERK mRNA, reduced the ceramide concentration in antigen-stimulated mast cells, and suppressed the passive cutaneous anaphylaxis (PCA) reaction in mice in a dose-dependent manner. These results suggest that eriodictyol can inhibit mast cell degranulation through inhibition of ceramide kinase, and that it might potentially serve as an anti-allergic agent.

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Background: To investigate the potential value of volumetric iodine quantification using preoperative dual-energy computed tomography (DECT) for predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Methods: This retrospective study included patients with single HCC treated through surgical resection who underwent preoperative DECT. Quantitative DECT features, including normalized iodine concentration (NIC) to the aorta and mixed-energy CT attenuation value in the arterial phase, were three-dimensionally measured for peritumoral and intratumoral regions: (i) layer-by-layer analysis for peritumoral layers (outer layers 1 and 2; numbered in close order from the tumor boundary) and intratumoral layers (inner layers 1 and 2) with 2-mm layer thickness and (ii) volume of interest (VOI)-based analysis with different volume coverage (tumor itself; VOI O1 , tumor plus outer layer 1; VOI O2 , tumor plus outer layers 1 and 2; VOI I1 , tumor minus inner layer 1; VOI I2 , tumor minus inner layers 1 and 2). In addition, qualitative CT features, including peritumoral enhancement and tumor margin, were assessed. Qualitative and quantitative CT features were compared between HCC patients with and without MVI. Diagnostic performance of DECT parameters of layers and VOIs was assessed using receiver operating characteristic curve analysis. Results: A total of 36 patients (24 men, mean age 59.9 ± 8.5 years) with MVI (n = 14) and without MVI (n = 22) were included. HCCs with MVI showed significantly higher NICs of outer layer 1, outer layer 2, VOI O1 , and VOI O2 than those without MVI (P = 0.01, 0.04, 0.02, 0.02, respectively). Among the NICs of layers and VOIs, the highest area under the curve was obtained in outer layer 1 (0.747). Qualitative features, including peritumoral enhancement and tumor margin, and the mean CT attenuation of each layer and each VOI were not significantly different between HCCs with and without MVI (both P > 0.05).

Atopic dermatitis (AD) is a chronic, allergic, and inflammatory skin disease associated with eczema and dermatitis symptoms. Our previous studies have reported that eriodictyol extract inhibits immunoglobulin E (IgE)/Ag-induced type I hypersensitivity by suppressing the activation of proinflammatory cytokines, such as interleukin-4 (IL-4), and the expression of ceramide kinase. In this study, we investigated the inhibitory effect of eriodictyol on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in ICR mice. Treatment with 2 mg/mL eriodictyol for DNCB-induced AD-like skin lesions in ICR mice improved scratching behavior and skin severity score. Histological analysis demonstrated that thickening of the skin lesions were significantly reduced in the eriodictyol-treated group. Also, eriodictyol suppressed the DNCB-mediated elevation of IgE serum levels. These results suggest that eriodictyol may be a potential therapeutic resource for AD and an adjunctive agent to control itchiness in AD.Key words atopic dermatitis; eriodictyol; skin severity; scratching behaviorThe rate of atopic dermatitis (AD) has been increasing recently in many industrialized countries and its occurrence is usually during early infancy and childhood, but can also be in adulthood.1,2) AD is a chronic, relapsing, and inflammatory skin disease in humans and is associated with eczematous symptoms and immunoglobulin E (IgE) hyperproduction. AD is caused by a complex interrelationship among genetic, immunologic, and skin barrier dysfunction factors. 3-5)The earliest event involved in the pathogenesis of AD is considered to be a disruption of skin barrier function after scratching. Itching is a serious problem in AD patients because scratching worsens the dermatitis.6) Reduction of itching-associated scratching is the most effective therapeutic strategy for improving the quality of life for AD patients.AD is associated with the paradigm of an allergic T helper (Th) 2-mediated disease, characterized by abnormal IgE production, peripheral eosinophilia, and mast cell activation as well as upregulation of Th2 and Th1 cytokines in chronic skin lesions. 7,8) Topical steroids and immunosuppressive agents have been standard treatments for severe cases of AD. However, many patients are still worried about the long-term use of these agents and their potential adverse effects.9-11) Therefore, there is a great need for the development of new and effective therapies for AD.Eriodictyol is a unique constituent of the painted maple (Acer mono) and yerba santa (Eriodictyon californicum). Pharmacological activities attributed to eriodictyol include the control of blood vessel permeability in arthralgia and fracture, as well as antioxidant and antimicrobial effects. 12,13) Recently, our previous studies demonstrated that eriodictyol inhibits IgE-mediated allergic responses by blocking degranulation associated with ceramide kinase. Also, we showed that eriodictyol inhibits anaphylactic shock in an animal model and blocks the release of inflammatory cytokines...