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A new neolignan, linderin A (1), together with six known lignans, (+)-xanthoxyol (2), pluviatilol (3), actiforin (4), (+)-syringaresinol (5), (+)-(7S,8R,8'R)-acuminatolide (6), and (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (7) were isolated from the stems of Lindera obtusiloba Blume (Lauraceae). Their chemical structures were elucidated by a combination of spectroscopic analysis and chemical reaction, and the absolute configuration of 1 was determined by Mosher's esterification. The effect of compounds 1-7 on tumor necrosis factor (TNF)-α, interleukin(IL)-6, and their inhibitory activity of histamine release were examined using human mast cells. Among the lignans tested, compounds 1, 3, 4, 6, and 7 inhibited release of histamine from mast cells. Especially, compounds 1 and 4 suppressed the gene expressions of pro-inflammatory cytokines, TNF-α, and IL-6 in human mast cells. Our findings suggest that the lignan constituents in L. obtusiloba may contribute to its anti-allergic inflammatory effects.

The aim of the present study was to elucidate whether extracts of Vigna angularis (EVA) inhibit allergic inflammatory reactions and to elucidate the possible mechanisms of action. For the assessment of allergic inflammatory response, histamine release and the expression of pro-inflammatory cytokines from human mast cells (HMC-1) were examined. To identify the underlying mechanisms of action, intracellular calcium and the activation of nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs) were assayed. To confirm the effects of EVA in vivo, systemic and local allergic reaction mouse models were employed. EVA dose-dependently reduced phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced histamine release from mast cells. The inhibitory effects of EVA on the release of histamine from mast cells were mediated by the reduction of intracellular calcium levels. EVA decreased the PMACI-stimulated gene expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6. The inhibitory effects of EVA on pro-inflammatory cytokines were NF-κB- and MAPK-dependent. In addition, EVA inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E (IgE)-mediated cutaneous anaphylaxis. Our findings provide evidence that EVA inhibits mast cell-derived allergic inflammation, and suggest the possible therapeutic application of EVA in allergic inflammatory disorders.

Ethnopharmacological Relevance: The Lindera obtusiloba has been used in traditional medicine for the treatment of inflammation and dermatitis. In this study, we investigated the effect of topical application of Lindera obtusiloba water extract (LOWE) on the house dust mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)., Materials and Methods: We established AD model in BALB/c mice by repeated local exposure of DFE/DNCB to the ears. After a topical application of LOWE on the skin lesions, the epidermal thickness, mast cell infiltration, and serum immunoglobulin E (IgE) and histamine were measured. In addition, the gene expression of interleukin (IL)-4, IL-13, IL-31, and tumor necrosis factor (TNF)-α in the ears was assayed., Results: LOWE reduced AD symptoms based on ear thickness, histopathological analysis, and serum IgE levels. LOWE inhibited mast cell infiltration into the ear and elevation of serum histamine in AD model. Moreover, LOWE suppressed DFE/DNCB-induced expression of IL-4, IL-13, IL-31, and TNF-α in the ears., Conclusions: Our results showed that topical application of LOWE exerts beneficial effects in AD symptoms, suggesting that LOWE might be a candidate for the treatment of AD., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Allergic disease is a consequence of exposure to normally innocuous substances that elicit the activation of mast cells. Mast-cell-mediated allergic response is involved in many diseases such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of Lindera obtusiloba water extract (LOWE) on the mast-cell-mediated allergic inflammation and possible mechanism of action using in vitro and in vivo models. LOWE reduced histamine release from various types of mast cells activated by immunoglobulin E (IgE) or phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI). The inhibitory effect of LOWE on histamine release was mediated by calcium signal. LOWE decreased the PMACI-stimulated gene expression of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in human mast cells. The inhibitory effect of LOWE on the proinflammatory cytokines was nuclear factor (NF)-κB dependent. In addition, LOWE suppressed compound 48/80-induced systemic allergic reaction and serum histamine release in mice and IgE-mediated local allergic reactions. Our results indicate that LOWE inhibits mast-cell-derived allergic inflammation and involvement of calcium, histamine, proinflammatory cytokines and NF-κB in these effects.