Inhibited Ear Swelling Research Articles

Preliminary Evaluation of the Acute and Sub-Acute Anti-Inflammatory Activities of Aqueous and Butanol Leaf Fractions of Olax subscorpioidea Oliv. (Olacaceae).

Olax subscorpioidea (Oliv.) leaf is widely used as a traditional remedy for pain, reduction of small tumors, edema, painful swellings, and other inflammatory conditions. Its anti-inflammatory potential in experimental animals has been documented. Furthermore, an anti-inflammatory assay guided fractionation showed that the aqueous and butanol leaf fractions were the most active. This study is aimed at investigating further, the acute and sub-acute anti-inflammatory potentials of the aqueous and butanol leaf fractions in mice and rats.Carrageenan induced paw edema in rats, xylene induced ear edema in mice, and cotton pellet induced granuloma in rats were the models employed for the studies. For each of the methods, four randomly-selected groups of animals (n=5/6) were orally administered with distilled water (1 ml/kg), aqueous or butanol fraction (1,000 mg/kg) and standard drugs (acetylsalicylic acid [ASA] 300 mg/kg or dexamethasone, 1 mg/kg).The aqueous and butanol fractions each showed significant (p < 0.01) inhibition of ear swelling, the fractions also significantly (p < 0.05, p < 0.01) decreased the paw edema, and significantly (p < 0.01) inhibited the granuloma formation.The result of the study suggests that aqueous and butanol leaf fractions of Olax subscorpioidea are effective against acute and sub-acute inflammation.

Immunosuppressive effect of hispidulin in allergic contact dermatitis

BackgroundLong-term use of most immunosuppressants to treat allergic contact dermatitis (ACD) generates unavoidable severe side effects, warranting discovery or development of new immunosuppressants with good efficacy and low toxicity is urgently needed to treat this condition. Hispidulin, a flavonoid compound that can be delivered topically due to its favorable skin penetrability properties, has recently been reported to possess anti-inflammatory and immunosuppressive properties. However, no studies have investigated the effect of hispidulin on Th1 cell activities in an ACD setting.MethodsA contact hypersensitivity (CHS) mouse model was designed to simulate human ACD. The immunosuppressive effect of hispidulin was investigated via ear thickness, histologic changes (i.e., edema and spongiosis), and interferon-gamma (IFN-γ) gene expression in 1-fluoro-2,4-dinitrobenzene (DNFB)-sensitized mice. Cytotoxicity, total number of CD4+ T cells, and percentage of IFN-γ-producing CD4+ T cells were also investigated in vitro using isolated CD4+ T cells from murine spleens.ResultsTopically applied hispidulin effectively inhibited ear swelling (as measured by reduction in ear thickness), and reduced spongiosis, IFN-γ gene expression, and the number of infiltrated immune cells. The inhibitory effect of hispidulin was observed within 6 h after the challenge, and the observed effects were similar to those effectuated after dexamethasone administration. Hispidulin at a concentration up to 50 μM also suppressed IFN-γ-producing CD4+ T cells in a dose-dependent manner without inducing cell death, and without a change in total frequencies of CD4+ T cells among different concentration groups.ConclusionThe results of this study, therefore, suggest hispidulin as a novel compound for the treatment of ACD via the suppression of IFN-γ production in Th1 cells.

Electroacupuncture inhibits mast cell degranulation via cannabinoid CB2 receptors in a rat model of allergic contact dermatitis.

Cannabinoid CB2 receptors (CB2Rs) are mainly present on immune cells including mast cells, which participate in 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD). In this study, we aimed to investigate whether inhibition of mast cell degranulation was involved in the anti-ACD effect of electroacupuncture (EA) at ST36 via CB2R. Sprague-Dawley rats were sensitised and challenged with DNFB following EA stimulation for 1 week. Ear swelling, serum IgE levels, local cytokine production and mast cell infiltration were evaluated. Additionally, rat peritoneal mast cells (RPMCs) were isolated and cultured for detection of CB2R expression, mitogen-activated protein kinase (MAPK) signalling activation and mast cell degranulation (including β-hexosaminidase and histamine release) in the presence or absence of CB2R antagonists. EA treatment inhibited ear swelling, suppressed IgE and cytokine production, decreased the number of mast cells and curbed mast cell degranulation, which was associated with the inhibition of p38 phosphorylation in DNFB-induced ACD. Importantly, EA enhanced the expression of CB2R mRNA and protein in the RPMCs. CB2R antagonist AM630 but not CB1R antagonist AM251 effectively reversed the suppressive effect of EA on p38 activation, mast cell infiltration and degranulation. These findings provide more evidence to support the hypothesis that EA promotes CB2R expression in mast cells, which is followed by inhibition of the p38 MAPK pathway, potentially resulting in the anti-ACD effect of EA. This suggests that EA at ST36 may be an effective candidate therapy for treating inflammatory skin diseases such as ACD.

Anti-inflammatory effects of new catechin derivatives in a hapten-induced mouse contact dermatitis model

Contact dermatitis is a common skin disease, with various treatments available to dermatologists. According to general guidelines, the first line of treatment involves topical steroids; however, this treatment has application-site restrictions in order to avoid adverse cutaneous events. Accordingly, increased demand exists for the development of new treatments. In Japan, the recent use of catechin-containing health foods and their beneficial effects has attracted attention. Indeed, several studies have examined the anticancer, anti-obesity, anti-inflammatory, and antioxidant effects of catechins. In this study, we synthesized planar catechin (PC) from natural (+)-catechin, and further chemically modified it with the intent to clarify the anti-inflammatory and antioxidant effects of new catechin derivatives. Methylate-PC (methyl PC) and acetylate-PC (acetyl PC) were modified to increase lipid solubility. Their antioxidant effects were examined with electron spin resonance by evaluating the ability to remove hydroxyl radicals. In vitro, the antioxidant effects were in the order of PC > (+)-catechin > acetyl PC > methyl PC. In addition, we used a 1-fluoro-2,4-dinitrobenzene (DNFB)-induced allergic contact dermatitis model in BALB/c mice. Our results demonstrated that catechin derivatives inhibited ear swelling induced by DNFB, with acetyl PC demonstrating a greater inhibitory effect than PC and methyl PC. Moreover, acetyl PC downregulated the mRNA levels of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-1β, and IL-4, as well as myeloperoxidase activity, in the ear tissue of DNFB-treated mice. Collectively, our novel findings suggest that catechin derivatives may be a promising new choice for the treatment of contact dermatitis.

Chlorogenic acid methyl ester exerts strong anti-inflammatory effects via inhibiting the COX-2/NLRP3/NF-κB pathway.

The objective of this study was to investigate the anti-inflammatory effect of chlorogenic acid methyl ester (CME) and the molecular mechanism involved, through using non-infectious inflammation and infectious inflammation animal models as well as lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cell models. Our results demonstrated that CME markedly inhibited ear swelling, paw swelling and granuloma swelling, and decreased intraperitoneal capillary permeability in non-infectious inflammation. Moreover, CME significantly alleviated the pathological damage of the lung tissue, reduced the levels of PGE2 and IL-1β in the serum and the protein expression levels of related-inflammatory factors in the lung tissue of LPS-induced mice with acute lung injury (ALI). In addition, CME affected the RAW264.7 cell cycle and inhibited the protein expressions of COX-2 and NLRP3 and prevented the phosphorylation of NF-κB p65 in RAW264.7 cells treated with LPS. These observations not only validated the anti-inflammatory effects of CME, but also revealed the underlying molecular basis, which involves the down-regulation of the expression of inflammatory factors and blockade of the COX-2/NLRP3/NF-κB signaling pathway.

Anti-inflammatory Effects of Brassica oleracea Var. capitata L. (Cabbage) Methanol Extract in Mice with Contact Dermatitis.

Background:Cabbage, Brassica oleracea var. capitata L., is one of the most common vegetables in the world. Because of its high levels of flavonoids and anthocyanins, cabbage has long been used as a herbal medicine. The antioxidant and anti-inflammatory properties of cabbage were also recently been reported.Objective:This study was designed to investigate the anti-inflammatory effects of cabbage in mice with contact dermatitis (CD).Materials and Methods:We investigated the effects of methanol extract of B. oleracea var. capitata L. (MEBO) on ear swelling, erythema, and histopathological changes in CD mice. Moreover, the effects on cytokine production and the spleen/body weight ratio were investigated.Results:Topical treatment with MEBO inhibited ear swelling and erythema significantly. MEBO also significantly inhibited epidermal hyperplasia and infiltration of immune cells. Furthermore, the levels of tumor necrosis factor-alpha, interferon-gamma, interleukin-6, and monocyte chemotactic protein-1 in inflamed tissues were effectively lowered by MEBO. Finally, MEBO did not affect body weight gain or spleen body weight ratio.Conclusions:These results indicate that cabbage can be used for the treatment of skin inflammation and that its anti-inflammatory activity is closely related to the inhibition of Th1 skewing reactions.SUMMARY MEBO inhibited ear thickness, weight, and erythema in inflamed skinMEBO also prevented epidermal hyperplasia and infiltration of immune cellsThe levels of tumor necrosis factor-α, interferon-γ, interleukin-6, and monocyte chemotactic protein-1 in inflamed tissues were lowered by MEBO. Abbreviations used: AOO: Acetone and olive oil (4:1), CBA: Cytometric bead array, CD: Contact dermatitis, DEX: Dexamethasone, DNFB: 1-fluoro-2,4-dinitrofluorobenzene, GM-CSF: Granulocyte-macrophage colony-stimulating factor, ICAM-1: Intercellular Adhesion Molecule-1, LPS: Lipopolysaccharide, MEBO: Methanol extract of Brassica oleracea, MCP-1: Monocyte chemotactic protein-1, NO: Nitric oxide.

Electro-Acupuncture at Zusanli Acupoint (ST36) Suppresses Inflammation in Allergic Contact Dermatitis Via Triggering Local IL-10 Production and Inhibiting p38 MAPK Activation.

Acupuncture has shown beneficial effect in the treatment of multiple dermatologic conditions including dermatitis, pruritus, urticaria, and hyperhidrosis; however, the detailed mechanisms are still kept unclear. This study aimed to investigate if electro-acupuncture (EA) treatment prevents 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in rats and explore its underlying mechanisms. ACD was induced by sensitizing and challenging with DNFB topically. Rats were treated daily following bilateral subcutaneous stimulation of EA at Zusanli acupoint (ST36) for 1week. Ear swelling and serum IgE levels were measured. The ear biopsies were obtained for histology. Inflammatory cytokines on the dermatological ear and local acupoint tissue were assayed. Spleen lymphocytes and the homogenized supernatant of local acupuncture area were used to co-culture for flow cytology and immune analysis, respectively. EA treatment at ST36 notably inhibited ear swelling and inflammatory cell infiltration on DNFB-induced ACD. EA also decreased serum IgE concentrations and alleviated the production of inflammatory cytokines in dermatological ear. Additionally, EA treatment attenuated the percentage of CD4+IFN-γ+ and CD4+IL-4+ T cells associated with ACD. Interestingly, secretion of interleukin (IL)-10 in the local acupoint tissue following EA stimulation was increased and showed suppressive function when co-cultured with the spleen lymphocytes from DNFB group. Lastly, EA treatment demonstrably suppressed p38 MAPK activation in DNFB-treated rats. Our findings suggest that EA treatment at ST36 may ameliorate inflammation associated with DNFB-induced ACD via triggering local IL-10 production and inhibiting p38 MAPK activation, which provide an alternative and promising therapy for ACD.

External application of NF-κB inhibitor DHMEQ suppresses development of atopic dermatitis-like lesions induced with DNCB/OX in BALB/c mice

Context: Dehydroxymethylepoxyquinomicin (DHMEQ) which is originally developed as an analog of antibiotic epoxyquinomicin C is a specific and potent inhibitor of NF-κB and has been shown to possess promising potential as an anti-inflammatory and anti-tumor agent.Objective: This study examines DHMEQ’s effect on therapeutic potential for atopic dermatitis (AD)-like lesions.Materials and methods: AD lesions were chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in BALB/c mice. The mice were then externally treated with DHMEQ ointment. Macroscopic and microscopic changes of the skin lesions were observed and recorded.Results: DHMEQ inhibited ear swelling and relieved clinical symptoms of the AD-like lesions induced by DNCB/OX in BALB/c mice. Histopathology examination illustrated that it significantly decreased DNCB/OX-induced epidermal thickness, the infiltration of inflammatory cells, and the count of mast cell. The elevated level of immunoglobulin E (IgE) in serum and the mRNA levels of interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-13 in the ear tissues, were also suppressed by DHMEQ.Discussion and conclusion: This study indicated that DHMEQ would be useful for the treatment of AD.

Drug-loaded poly(d,l-lactide-co-glycolide) microspheres as treatment for allergic contact dermatitis in mice model

Allergic contact dermatitis is a common skin disease and the current treatment always along with frequent medication and side effect. In this research, poly(d,l-lactide- co-glycolide) microspheres encapsulating tacrolimus are first employed as a therapy of allergic contact dermatitis in mice model by subcutaneous injection. Allergic contact dermatitis is successfully induced in BALB/c mice by repeated painting of dinitrofluorobenzene on mice ear. Tacrolimus is efficiently encapsulated into poly(d,l-lactide- co-glycolide) microspheres by emulsion evaporation method, and then the microspheres are subcutaneously injected into dermatitis-suffered BALB/c mice. We find that the dermatitis mice treated with tacrolimus-loaded microspheres get a sustained suppression on ear swelling, dermatitis index, inflammatory cell accumulation, and serum immunoglobulin E concentration. The curative effect of tacrolimus-loaded microspheres is similar to daily tacrolimus injection and is even better in the inhibition of ear swelling. Dermatitis mice treated with blank microspheres get no curative effect during the whole experiment. The data suggest that subcutaneous injection of drug-loaded microspheres could be a potential candidate for the management of allergic contact dermatitis.

A novel compound 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide downregulates TSLP through blocking of caspase-1/NF-κB pathways

Thymic stromal lymphopoietin (TSLP) is regarded as the main factor responsible for the pathogenesis of allergic disorders such as atopic dermatitis, chronic obstructive pulmonary diseases, and allergic rhinitis. As part of our continuing search for novel anti-inflammatory compounds, 2-(4-{2-[(phenylthio)acetyl]carbonohydrazonoyl}phenoxy)acetamide (PA) was analyzed. In the present study, we examined how PA regulates the mRNA expression and production of TSLP in the human mast cell line, HMC-1 cells. Computer-aided docking simulation, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, caspase-1 assay, and Western blotting were used to investigate the effects of PA. PA decreased the mRNA expression and production of TSLP in HMC-1 cells. PA (1μM) inhibited the TSLP production up to 87.710±5.201%. PA also improved the activation and phosphorylation of nuclear factor-κB as well as the degradation and phosphorylation of IκBα. Caspase-1 activation was up-regulated in activated HMC-1 cells, whereas caspase-1 activation was down-regulated by PA. Finally, PA inhibited ear swelling response induced by phorbol myristate acetate in mice. These results indicate that PA would be effective to treat inflammatory and atopic disorders through the down-regulations of TSLP.

Effect of 6'-acetylpaeoniflorin on dinitrochlorobenzene-induced allergic contact dermatitis in BALB/c mice.

Allergic contact dermatitis (ACD) is a classical experimental model of allergic inflammatory skin disease, which is a delayed-type hypersensitivity reaction that is mediated by hapten-specific T lymphocytes. The goal of this study was to investigate the pharmacokinetic profiles of 6'-acetylpaeoniflorin (6-AP) and the effect of 6-AP on the ACD model. 6-AP was synthesized from paeoniflorin (Pae) via acetylation, and the structure was confirmed. There were statistically significant differences in the pharmacokinetic parameters including t 1/2α , t 1/2β , AUC, MRT and C max among the animals that were orally administered Pae and 6-AP. An ACD model was induced using immunization with dinitrochlorobenzene (DNCB) in BALB/c mice. The mice were orally administered 6-AP (35, 70 and 140mg/kg/d), Pae (70mg/kg/d) and prednisone (Pre, 5mg/kg/d) from day 1 to day 7 after immunization. The results indicated that the topical application of DNCB to the skin provoked obvious inflammatory responses. 6-AP significantly inhibited ear swelling and decreased inflammatory cell infiltration and epidermal keratinization. Additionally, 6-AP observably alleviated the hyperplasia of red pulp and germinal center appearance, decreased the spleen index and inhibited splenocyte proliferation in the ACD model compared to that of Pae. Furthermore, the study indicated that 6-AP could increase the IL-10 level, while simultaneously reducing the IL-17 level in splenocytes. In summary, these results suggest that 6-AP has a significantly higher anti-inflammatory effect than Pae and that 6-AP might be a candidate for the treatment of allergic skin diseases.

Aspartame Attenuates 2, 4-Dinitrofluorobenzene-Induced Atopic Dermatitis–Like Clinical Symptoms in NC/Nga Mice

Atopic dermatitis (AD) is a common multifactorial chronic skin disease that has a multiple and complex pathogenesis. AD is gradually increasing in prevalence globally. In NC/Nga mice, repetitive applications of 2, 4-dinitrofluorobenzene (DNFB) evoke AD-like clinical symptoms similar to human AD. Aspartame (N-L-α-aspartyl-L-phenylalanine 1-methyl ester) is a methyl ester of a dipeptide, which is used as an artificial non-nutritive sweetener. Aspartame has analgesic and anti-inflammatory functions that are similar to the function of nonsteroidal anti-inflammatory drugs such as aspirin. We investigated whether aspartame can relieve AD-like clinical symptoms induced by DNFB treatment in NC/Nga mice. Sucrose did not relieve AD-like symptoms, whereas aspartame at doses of 0.5 μg kg(-1) and 0.5 mg kg(-1) inhibited ear swelling and relieved AD-like clinical symptoms. Aspartame inhibited infiltration of inflammatory cells including eosinophils, mast cells, and CD4(+) T cells, and suppressed the expression of cytokines including IL-4 and IFN-γ, and total serum IgE levels. Aspartame may have therapeutic value in the treatment of AD.

Effects of Schisandra chinensis Turcz. fruit on contact dermatitis induced by dinitrofluorobenzene in mice.

Schisandra chinensis Turcz. fruit is widely used to treat skin diseases. The aim of this study was to determine the anti-inflammatory effects of the methanol extract of S. chinensis (MESC) on 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis (CD) in mice. The effects of MESC on ear thickness and weight, histopathological changes, immune cell filtration and cytokine production were investigated in DNFB-induced CD mice. Topical application of MESC effectively inhibited ear swelling (30 or 300 μg on the left ear, P<0.001; 30 μg on the right ear, P<0.001). MESC also inhibited hyperplasia, spongiosis (100 μg/ear, P<0.05 and 300 μg/ear, P<0.001, respectively) and immune cell infiltration (100 μg/ear, P<0.05; 300 μg/ear, P<0.001) induced by DNFB. In addition, MESC suppressed increases in tumor necrosis factor (TNF)-α levels (100 or 300 μg/ear, P<0.05), interferon (INF)-γ (30 μg/ear, P<0.05; 100 μg/ear, P<0.01; 300 μg/ear, P<0.001), interleukin (IL)-6 (300 μg/ear, P<0.05) and monocyte chemoattractant protein (MCP)-1 (30 μg/ear, P<0.05; 100 μg/ear, P<0.01; 300 μg/ear, P<0.001). These results suggest that the anti-inflammatory effects of MESC are mediated by the reduced production of TNF-α, IFN-γ, IL-6 and MCP-1, and that MESC has potential use for the treatment of inflammatory skin diseases.

Inhibition of Neurite Outgrowth by a Neuropilin-1 Binding Peptide Derived from Semaphorin 3A

Semaphorin 3A (Sema3A), an axon guidance molecule, inhibits neurite outgrowth of sensory neurons. Recombinant Sema3A protein has also inhibited scratching behavior and improved skin inflammation in an atopic dermatitis model. In the present study, we investigated whether Sema3A-derived peptides could bind its receptor, neuropilin-1 (NRP1), to inhibit neurite outgrowth. Here, two candidate NRP1-binding (NPB) peptides, NPB7 and NPB15, were found to inhibit NGF-induced survival and neurite outgrowth of PC12 cells and rat primary neurons in serum-free medium. To investigate the preventive effect of the two NPB peptides in vivo, we assessed whether they could inhibit skin inflammation induced by repeated topical application of oxazolone in mice. NPB15 peptide, but not NPB7, inhibited ear swelling. The NPB15 peptide solution and Vaseline ointment groups showed slightly decreased epidermal nerve densities compared with controls. The combination of NPB15 peptide and Vaseline ointment increased the inhibitory effect of NPB15 peptide on epidermal nerve densities. These results suggest that Sema3A-derived peptides can bind to NRP1 and inhibit neurite outgrowth both in vitro and in vivo. Thus, these peptides may be potent candidates for the treatment of atopic dermatitis.

Attenuated Bordetella pertussis BPZE1 protects against allergic airway inflammation and contact dermatitis in mouse models

We previously reported that prior nasal administration of highly attenuated Bordetella pertussis BPZE1 provides effective and sustained protection against lethal challenge with influenza A viruses. The protective effect was mediated by suppressing the production of major pro-inflammatory mediators. To further explore the anti-inflammatory properties of BPZE1, we investigated the effect of BPZE1 nasal pretreatment on two mouse models of allergic disease, allergic airway inflammation, and contact hypersensitivity (CHS). Allergic reactions were induced in mice nasally pretreated with live attenuated BPZE1 bacteria using the ovalbumin (OVA)-induced allergic airway inflammation and dinitrochlorobenzene (DNCB)-induced CHS models. Prior BPZE1 nasal treatment suppressed OVA-induced lung inflammation and inflammatory cell recruitment and significantly reduced IgE levels and cytokine production. Similarly, BPZE1 nasal pretreatment markedly inhibited ear swelling, skin inflammation, and production of pro-inflammatory cytokines in the DNCB-induced CHS model. For both models, we showed that BPZE1 pretreatment does not affect the sensitization phase. Upon challenge, BPZE1 pretreatment selectively reduced the level of cytokines whose production is increased and did not affect the basal level of other cytokines. Together, our observations suggest that BPZE1 pretreatment specifically targets those cytokine-producing effector cells that are recruited and involved in the inflammatory reaction. Our study demonstrates the broad anti-inflammatory properties of the attenuated B. pertussis BPZE1 vaccine candidate and supports its development as a promising agent to prevent and/or treat allergic diseases.

Red Ginseng Inhibits Scratching Behavior Associated With Atopic Dermatitis in Experimental Animal Models

Pruritus is a severe symptom that is difficult to treat in atopic dermatitis patients. Red ginseng (RG), a natural medicine, has various biological activities such as anti-inflammatory effects. In this study, we examined the efficacy of RG extract (RGE) and its mechanism on experimental atopic dermatitis in mice. The effects of RGE on vascular permeability and itching were first evaluated. Histamine-induced permeability and itching were significantly inhibited by embrocation with RGE as well as diphenhydramine, an antihistamine drug. Next, we assessed the therapeutic effect of topical RGE in a mouse model of atopic dermatitis. Dermatitis was induced by repeated application of 2,4-dinitrofluorobenzene (DNFB) acetone solution to the mouse ear. The effects of tacrolimus (a calcineurin blocker), dexamethasone (a corticosteroid), and RGE on dermatitis and associated scratching behavior were compared. Repeated DNFB application caused frequent scratching behaviors and ear swelling. Topical treatment with tacrolimus, dexamethasone, and RGE for 8 days before the final challenge with DNFB significantly inhibited ear swelling. Tacrolimus and RGE significantly inhibited scratching behavior, whereas dexamethasone failed to do so. DNFB-induced nerve growth factor expression and nerve fiber extension were significantly attenuated by tacrolimus and RGE, but not by dexamethasone. RGE may have the potential for treatment of atopic dermatitis.

Inhibitory Effect of Dietary Carotenoids on Dinitrofluorobenzene-Induced Contact Hypersensitivity in Mice

We evaluated the effect of carotenoids on the dinitrofluorobenzene (DNFB)-induced contact hypersensitivity in mice. Dietary carotenoids significantly inhibited ear swelling and reduced the contents of TNF-α and histamine in the DNFB-treated mice. Our results suggest that dietary carotenoids exerted an anti-inflammatory effect by suppressing mast cell degranulation in vivo.

Anti-inflammatory Effects of Aqueous Extract from Radix Liriope muscari and Its Major Active Fraction and Component

Aim To investigate the anti-inflammatory activities of the aqueous extract from Liriope muscari (Decne.) Bailey (Lm-a), its crude saponin fraction (Lm-s) and one major component (Lm-3), and to provide some pharmacological evidence for its clinical use in inflammatory diseases. Methods The anti-inflammatory activities of Lm-a, Lm-s and Lm-3 were evaluated by xylene-induced ear swelling and paw edema induced by carrageenan or histamine in mice. Meanwhile, the activity of Lm-3 was also determined by assaying the adhesion of human pro-myelocytic leukemia cell strain (HL-60) to human umbilical vein endothelial cell line (ECV304) induced by tumor necrosis factor (TNF-α) or phorbol-12-myristate-13-acetate (PMA) in vitro. Results Lm-a significantly inhibited ear swelling caused by xylene and paw edema induced by carrageenan in mice when given orally once at doses of 336 and 672 mg·kg −1. Meanwhile, Lm-s and Lm-3 possessed similar remarkable anti-inflammatory effects in such two animal models at a single oral dose of 23.2 or 4.6 mg·kg −1 (relevant to Lm-a 672 mg·kg −1), respectively. Moreover, Lm-3 markedly suppressed acute paw edema induced by histamine in mice when given orally once at the dose of 4.6 mg·kg −1, whose potency was similar to that of Lm-a or Lm-s at a single oral dose of 672 or 23.2 mg·kg −1. Lm-3 also significantly inhibited the adhesion of HL-60 to ECV304 cells induced by TNF-α or PMA at the concentrations of 0.01, 0.1 and 1 μmol·L −1 in vitro, which suggested the involved role of protein kinase C etc. Conclusion Lm-a, Lm-s and Lm-3 have the anti-inflammatory activities, which offers pharmacological supports to the ethnomedical use of the roots of L. muscari in inflammatory diseases and reveals the major attribution of saponins-rich fraction including Lm-3.

Oral Glucosylceramide Reduces 2,4‐Dinitrofluorobenzene Induced Inflammatory Response in Mice by Reducing TNF‐Alpha Levels and Leukocyte Infiltration

Sphingolipids are constituents of cellular membranes and play important roles as second messengers mediating cell functions. As significant components in foods, sphingolipids have been proven to be critical for human health. Moreover, diverse metabolic intermediates of sphingolipids are known to play key roles both in proinflammatory and in anti-inflammatory effects. However, the effect of dietary sphingolipids on inflammation is a complicated field that needs to be further assessed. Our study evaluated the effects of orally administered maize glucosylceramide (GluCer), one of the most conventional dietary sphingolipids, on inflammation using the 2,4-dinitro-1-fluorobenzene-treated BALB/c murine model. Oral administration of GluCer inhibited ear swelling and leukocyte infiltration to the inflammatory site, suggesting that dietary GluCer has anti-inflammatory properties. ELISA analyses revealed that oral administration of GluCer for 6days had not modified the Th1/Th2 balance, but significantly down-regulated the activation of TNF-α at the inflammatory site. Based on these results, the down-regulation of TNF-α by dietary GluCer may suppress vascular permeability and reduce the migration of inflammatory cells. Our findings increase understanding of the actions of dietary sphingolipids on the balance of the immune response.

Thymic Stromal Lymphopoietin Is Required for Gastrointestinal Allergy but Not Oral Tolerance

Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that acts on dendritic cells, mast cells, T cells, and B cells. TSLP is involved in the pathogenesis of allergic inflammation in the lung and skin, but data indicate a regulatory role in the gastrointestinal tract. We tested the functional role of TSLP in mouse models of gastrointestinal allergy and tolerance. TSLP Receptor (TSLPR)(+/+) and TSLPR(-/-) mice were sensitized and challenged with ovalbumin; models of allergic diarrhea or systemic anaphylaxis were studied. To induce oral tolerance, mice were fed with low-dose ovalbumin before they were immunized with it. Tolerance was measured from inhibition of ear swelling in a delayed-type hypersensitivity reaction. TSLPR(-/-) mice were protected from the onset of allergic diarrhea; they did not develop mastocytosis in the jejunum and had reduced ovalbumin-immunoglobulin E in their serum, compared with TSLPR(+/+) mice. TSLPR(-/-) mice also lost T helper cell (Th) 2-mediated inflammation in the jejunum. In contrast, sensitization and oral tolerance were not impaired in TSLPR(-/-) mice. Transfer of wild-type, Th2-primed cells to TSLPR(-/-) mice completely restored the development of allergic diarrhea. Antigen presentation assays showed that TSLPR on T cells, but not dendritic cells, was required to mediate the Th2 response. TSLP is required for allergic inflammation but not primary sensitization or tolerance to food proteins in the gastrointestinal tract; it amplifies Th2 responses directly from CD4(+) T cells.