Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus.

We investigated the effect of an aqueous extract of Cichorium intybus (CIAE) on mast cell-mediated immediate type allergic reactions. CIAE (0.1-1000 mg kg-1) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. Especially, CIAE inhibited compound 48/80-induced anaphylactic reaction 100% with the dose of 1000 mg kg-1. CIAE 1000 mg kg-1also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with CIAE at a concentration ranging from 0.1 to 1000 mg kg-1, the plasma histamine levels were reduced in a dose-dependent manner. CIAE (1-1000 microg ml-1) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when CIAE (1000 microg ml-1) was added, increased significantly compared with that of control cells. These results indicate that CIAE inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.     

The pharmacological correction of recurrent immediate-type allergic reactions]

The effect of drugs on the early and late phases of repeated allergic reactions (RAR) was studied in experiments on rabbits. The action of the drugs was estimated by the number of challenge doses of antigen, endured by survived and dead rabbits, percentage of the animals' death, and by the place of each group on the lethality scale. Diphenhydramine, ouabain and their combinations, silver nitrate (20 mg/kg) and DOCA enhanced whereas histamine, unithiol, cholesterol, and silver nitrate (20 and 0.2 mg/kg) decreased allergization in the period of RAR. The characteristic features of the action of the drugs on RAR were revealed and compared to the first allergic reaction. Qualitative and quantitative differences were shown in the action of different drug doses and combinations on RAR. The authors provide evidence for the possibility of treating allergic diseases by drug administration in a quiet period.     

Lavender oil inhibits immediate-type allergic reaction in mice and rats

We studied the effects of lavender oil on mast cell-mediated immediate-type allergic reactions in mice and rats. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 in mice by both topical and intradermal application. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by both topical and intradermal application. Lavender oil (1:500, 1:100, 1:10, 1:1, 1:0) also inhibited concentration-dependently the histamine release from the peritoneal mast cells by compound 48/80 or anti-DNP IgE. Moreover, lavender oil (1:1000, 1:100, 1:10, 1:0) had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-alpha secretion from peritoneal mast cells. These results indicate that lavender oil inhibits immediate-type allergic reactions by inhibition of mast cell degranulation in-vivo and in-vitro.     

Diospyros kaki calyx inhibits immediate-type hypersensitivity via the reduction of mast cell activation

Context: Diospyros kaki L. (Ebenaceae) fruit is widely distributed in Asia and is known to exert anti-inflammatory and antithrombotic effects.

Objective: We evaluated the inhibitory effect of aqueous extract of D. kaki calyx (AEDKC) on mast cell-mediated immediate-type hypersensitivity and underlying mechanism of action.

Materials and methods: For in vivo, ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models were used. In the ASA, AEDKC (1–100?mg/kg) was orally administered 3 times during 14 days. In the PCA, AEDKC was orally treated 1?h before the antigen challenge. The control drug dexamethasone was used to compare the effectiveness of AEDKC. For in vitro, IgE-stimulated RBL-2H3 cells and primary cultured peritoneal mast cells were used to determine the role of AEDKC (0.01–1?mg/mL).

Results: Oral administration of AEDKC dose dependently suppressed rectal temperature decrease and increases in serum histamine, total IgE, OVA-specific IgE, and interleukin (IL)-4 in the ASA. In the PCA, AEDKC reduced Evans blue pigmentation. Compared to dexamethasone (10?mg/kg), AEDKC (100?mg/kg) showed similar inhibitory effects in vivo. AEDKC concentration dependently suppressed the release of histamine and β-hexosaminidase through the reduction of intracellular calcium in mast cells. In addition, AEDKC decreased the expression and secretion of tumour necrosis factor-α and IL-4 by the reduction of nuclear factor-κB. The inhibitory potential of AEDKC (1?mg/mL) was similar with dexamethasone (10?μM) in vitro.

Conclusions: We suggest that AEDKC may be a potential candidate for the treatment of mast cell-mediated allergic diseases.     

Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell-dependent stimulation of Jurkat T cells

Background and purpose:

Allergic inflammation and autoimmune diseases, such as atopic dermatitis, psoriasis and multiple sclerosis (MS), involve both mast cell and T-cell activation. However, possible interactions between the two and the mechanism of such activations are largely unknown.

Experimental approach:

Human umbilical cord blood-derived cultured mast cells (hCBMCs) and Jurkat T cells were incubated separately or together, following activation with myelin basic protein (MBP), as well as with or without pretreatment with the flavonoid luteolin for 15 min. The supernatant fluid was assayed for inflammatory mediators released from mast cells and interleukin (IL)-2 release from Jurkat cells.

Key results:

MBP (10 μM) stimulates hCBMCs to release IL-6, IL-8, transforming growth factor (TGF)-β1, tumour necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), histamine and tryptase (n=6, P<0.05). Addition of mast cells to Jurkat cells activated by anti-CD3/anti-CD28 increases IL-2 release by 30-fold (n=3, P<0.05). MBP-stimulated mast cells and their supernatant fluid further increase Jurkat cell IL-2 release (n=3, P<0.05). Separation of mast cells and activated Jurkat cells by a Transwell permeable membrane inhibits Jurkat cell stimulation by 60%. Pretreatment of Jurkat cells with a TNF-neutralizing antibody reduces IL-2 release by another 40%. Luteolin pretreatment inhibits mast cell activation (n=3–6, P<0.05), Jurkat cell activation and mast cell-dependent Jurkat cell stimulation (n=3, P<0.05).

Conclusions and implications:

Mast cells can stimulate activated Jurkat cells. This interaction is inhibited by luteolin, suggesting that this flavonoid may be useful in the treatment of autoimmune diseases.     

花青素对IgE介导的肥大细胞活化的影响

观察花青素 (anthocyanidin) 对肥大细胞活化脱颗粒的影响。通过大鼠被动皮肤过敏反应 (PCA) 实验, 采用比色测定法检测花青素在体内对肥大细胞的影响; 体外观察花青素对肥大细胞脱颗粒, 细胞内钙摄入, 肿瘤坏死因子-α (TNF-α) 及白细胞介素6 (IL-6) 释放以及p38MAPK、Akt、NF-κB磷酸化的影响。动物实验显示, 花青素 (50和100 mg·kg⁻¹) 明显抑制大鼠PCA。细胞实验显示, 花青素 (50和100 µmol·L⁻¹) 抑制肥大细胞释放组胺、TNF-α及IL-6, 并可抑制 p38MAPK、Akt和NF-κB的磷酸化。结果提示, 花青素的抗过敏作用与其抑制肥大细胞的脱颗粒, 抑制组胺、TNF-α、IL-6等炎症介质释放以及抑制细胞内钙摄入有关; 花青素抑制肥大细胞的活化可能与其抑制NF-κB、p38MAPK和Akt的活性相关。     

Mosla dianthera inhibits mast cell-mediated allergic reactions through the inhibition of histamine release and inflammatory cytokine production

In this study, we investigated the effect of the aqueous extract of Mosla dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-alpha, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. AEMD decreased PMA and A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-kappaB in these effects.     

C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressor agents.

Neuropeptide Y (NPY) is a well-established vasopressor agent present in sympathetic perivascular nerves. Recently, it was found that high doses of the peptide cause a biphasic pressor-depressor response upon intravenous administration. We now report that C-terminal NPY fragments (NPY-(18-36) and NPY-(22-36] given intravenously to conscious or pithed (areflexive) male Sprague-Dawley rats mimic the depressor component of the NPY-(1-36) response while displaying very low pressor activity. Additionally, we have found that the depressor component is blocked by the histamine H1-antagonist, mepyramine. Since the fragment, NPY-(22-36), was equipotent with NPY in inducing histamine release from isolated peritoneal mast cells, we conclude that short C-terminal NPY fragments, like NPY itself, act on mast cells to initiate histamine-mediated cardiovascular actions. Such actions may conceivably be accounted for by the abundance of positively charged amino acid residues in the C-terminus. Moreover, these fragments have little affinity for vascular NPY receptors, as indicated by their poor ability to displace iodinated NPY or peptide YY (PYY) from specific binding sites on vascular smooth muscle cells derived from rat aorta. In conclusion, we propose that short C-terminal NPY fragments, which contain several positively charged amino acid residues, retain the ability of NPY to release histamine from rat mast cells while being essentially devoid of direct vascular motor activity.     

Inhibition of mast cell-dependent anaphylaxis by succinic acid

We have examined the effect of succinic acid on anaphylaxis. Succinic acid (100 mM) significantly inhibited systemic anaphylaxis induced by compound 48/80 in mice and dose-dependently inhibited local anaphylaxis activated by anti-dinitrophenyl IgE. Further 10 and 100 mM significantly inhibited histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-dinitrophenyl IgE. In addition succinic acid (0.1 and 1 mM) had a significant inhibitory effect on anti-dinitrophenyl IgE-induced tumour necrosis factor-alpha secretion from rat peritoneal mast cells. The level of cyclic AMP in rat peritoneal mast cells, when succinic acid (100 mM) was added, transiently and significantly increased about 4 times compared with that of basal cells. These results suggest a possible use of succinic acid in managing mast cell-dependent anaphylaxis.     

Inhibitory effect of mast cell-dependent anaphylaxis byGleditsia sinensis

We investigated the effect of aqueous extract of Gleditsia sinensis thorns (Leguminosae) (GSAE) on the mast cell-dependent anaphylaxis. GSAE (0.005 to 1 g/kg) dose-dependently inhibited systemic anaphylaxis induced by compound 48/80 in rats. GSAE (0.1 and 1 g/kg) also significantly inhibited local anaphylaxis activated by anti-DNP IgE. When GSAE was pretreated at the same concentrations with systemic anaphylaxis, the plasma histamine levels were reduced in a dose-dependent manner. GSAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, When CSAE (1 mg/ml) was added, transiently and significantly increased about fourfold compared with that of basal cells. Moreover, GSAE (0.01 and 0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results suggest a possible use of GSAE in managing mast cell-dependent anaphylaxis.     

The protective effect of Tinospora cordifolia on various mast cell mediated allergic reactions

This study investigated the effect of an aqueous extract of Tinospora cordifolia (Willd.) Miers (Menispermaceae) stem on mast cell mediated allergic reactions in vivo and in vitro and studied its possible mechanism. T. cordifolia (125 to 1000?mg/kg) dose-dependently inhibited compound 48/80 induced lethality in rats, histamine induced paw edema in mice and histamine induced bronchial asthma in guinea pigs. T. cordifolia significantly (p?<?0.001) inhibited the cutaneous anaphylaxis reaction activated by histamine in a rat model and compound 48/80 induced ear swelling response in mice. T. cordifolia (2.5-160?μg/mL) also showed significant (p?<?0.001) inhibition of histamine induced contraction of guinea-pig ileum in vitro implying the H₁ antihistamine activity. T. cordifolia (0.01 to 10?mg/mL) significantly (p?<?0.001) inhibited the histamine release from rat peritoneal mast cells activated by compound 48/80. In addition, T. cordifolia (0.01 to 10?mg/mL) significantly (p?<?0.001) inhibited the secretion of tumor necrosis factor-α (TNF-α) in antidinitrophenyl (DNP) IgE-stimulated rat peritoneal mast cells. The level of cAMP in RPMC transiently and significantly increased compared with that of control cells when T. cordifolia was incubated with mast cells. T. cordifolia (0.01 to 10?mg/mL) showed concentration-dependent inhibition in compound 48/80 induced reactive oxygen species (ROS) generation. In addition, T. cordifolia decreased intracellular calcium levels of activated mast cells. These results show that T. cordifolia may be beneficial in the treatment of acute and chronic allergic disorders.     

Suppression of mast cell-mediated allergic reaction by Amomum xanthiodes.

The mast cell-mediated immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. Stimulation of mast cells starts the process of degranulation resulting in release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of aqueous extract of Amomum xanthiodes (Zingiberaceae) (AXE) on the mast cell-mediated allergy model and studied its possible mechanisms of action. AXE inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. AXE decreased immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis reaction. AXE reduced histamine release and intracellular calcium from rat peritoneal mast cells activated by compound 48/80. Furthermore, AXE decreased the activation of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase and c-jun N-terminal kinase, and downstream tumor necrosis factor (TNF)-alpha production in phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cells. Our findings provide evidence that AXE inhibits mast cell-derived allergic reactions, and that intracellular calcium, TNF-alpha, and p38 MAPK are involved in these effects.     

Progesterone inhibits mast cell secretion

Mast cells are involved in allergic reactions, where they secrete numerous vasoactive, inflammatory and nociceptive mediators in response to immunoglobulin E (IgE) and antigen. However, they have also been implicated in inflammatory conditions, such as painful bladder syndrome/interstitial cystitis (PBS/IC), irritable bowel syndrome (IBS) and migraines, all of which occur more often in women and are exacerbated during ovulation, but are suppressed during pregnancy. Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy.     

Galangin attenuates mast cell-mediated allergic inflammation

A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. In this study, we investigated anti-allergic inflammatory effect of galangin and underlying mechanisms of action using in vitro and in vivo models. Galangin inhibited histamine release by the reduction of intracellular calcium in phorbol 12-mystate 13-acetate plus calcium ionophore A23187-stimulated human mast cells (HMC-1). Galangin decreased expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8. The inhibitory effect of galangin on theses pro-inflammatory cytokines was related with c-Jun N-terminal kinases, and p38 mitogen-activated protein kinase, nuclear factor-κB, and caspase-1. Furthermore, galangin attenuated IgE-mediated passive cutaneous anaphylaxis and the expression of histamine receptor 1 at the inflamed tissue. The inhibitory effects of galangin were more potent than cromolyn, a known anti-allergic drug. Our results showed that galangin down-regulates mast cell-derived allergic inflammatory reactions by blocking histamine release and expression of pro-inflammatory cytokines. In light of in vitro and in vivo anti-allergic inflammatory effects, galangin could be a beneficial anti-allergic inflammatory agent.     

Prednisolone inhibits an IgE-mediated late-phase allergic cutaneous reactionby interfering with the activation of mast cells in mice

Epicutaneous antigen challenge in passively sensitized mice with IgE produces a biphasic cutaneous response which peaks 1 h (immediate-phase reaction) and 24 h (late-phase reaction; LPR) after the antigen challenge. In this model, anaphylactic degranulation and interleukin 6 (IL-6) expression between 4 and 8 h are observed in resident mast cells as the preceding stage of LPR. Prednisolone at a dose of 3 mg kg(-1) clearly inhibited the LPR when administered 2 h before and 4 h after antigen challenge. Slight or no inhibition of LPR was observed by prednisolone administered 6-12 h after challenge. Histologically, prednisolone treatment 2 h before antigen challenge completely inhibited edema and inflammatory cell infiltration, while treatment at 6 h did not at all. In order to investigate the relationship between inhibition of LPR by prednisolone and mast cell activation, the effects of prednisolone on degranulation of mast cells and IL-6 expression in mast cells were investigated. 8 h after antigen challenge, prednisolone clearly inhibited the increase in the number of anaphylactic degranulated and IL-6-positive mast cells by administration 2 h before challenge, but did not affect it by administration 6 h after challenge. These data indicate that the inhibitory mechanism of prednisolone on LPR, at least, involves the inhibition of mast cell activation before LPR.     

β‐eudesmol suppresses allergic reactions via inhibiting mast cell degranulation

The regulatory effect of β‐eudesmol, which is an active constituent of Pyeongwee‐San (KMP6), is evaluated for allergic reactions induced by mast cell degranulation. Phorbol 12‐myristate 13‐acetate (PMA) plus calcium ionophore A23187‐stimulated human mast cell line, HMC‐1 cells, and compound 48/80‐stimulated rat peritoneal mast cells (RPMCs) are used as the in vitro models; mice models of systemic anaphylaxis, ear swelling, and IgE‐dependent passive cutaneous anaphylaxis (PCA) are used as the in vivo allergic models. The results demonstrate that β‐eudesmol suppressed the histamine and tryptase releases from the PMA plus calcium ionophore A23187‐stimulated HMC‐1 cells. β‐eudesmol inhibits the expression and activity of histidine decarboxylase in the activated HMC‐1 cells. In addition, β‐eudesmol inhibits the levels of histamine and tryptase released from the compound 48/80‐stimulated RPMCs. Furthermore, β‐eudesmol decreases the intracellular calcium level in the activated RPMCs. β‐eudesmol also decreases the compound 48/80‐induced mortality and ear swelling response. β‐eudesmol suppresses the serum levels of histamine, IgE, interleukin (IL)‐1β, IL‐4, IL‐5, IL‐6, IL‐13, and vascular endothelial growth factor (VEGF) under PCA mice as well as PCA reactions. Therefore, the results from this study indicate the potential of β‐eudesmol as an anti‐allergic drug with respect to its pharmacological properties against mast cell‐mediated allergic reactions.     

T cell-dependent immune reactions to reactive benzene metabolites in mice

Using the popliteal lymph node (PLN) assay in mice, we studied the sensitizing potential of benzene and its metabolites. Whereas benzene and phenol failed to induce a PLN reaction, catechol and hydroquinone induced a moderate, and p-benzoquinone a vigorous response. Following a single injection of the reactive metabolite p-benzoquinone (100 nmol/mouse), cellularity in the draining PLN was increased >15-fold, and reverted back to normal only after ∼100 days. Although the PLN response was T cell-dependent, flow cytometric analysis revealed that the increased cellularity in the PLN after a single injection of p-benzoquinone was mainly due to an increase in B cells. Mice primed to p-benzoquinone and challenged with a small dose of p-benzoquinone (0.1 nmol/mouse) mounted a secondary PLN reaction, indicating hapten specificity of the reaction; this was confirmed by results obtained in the adoptive transfer PLN assay. An unexpected finding was the secondary PLN response to benzene (1 nmol/mouse) observed in mice primed to p-benzoquinone. This finding suggests that some of the benzene (at least 10%) was locally converted into p-benzoquinone, which then elicited the secondary response observed. In conclusion, the reactive intermediate metabolites hydroquinone and p-benzoquinone can act as haptens and sensitize; their precursors, benzene and phenol, may be considered as prohaptens. Received: 7 December 1998 / Accepted: 9 February 1999     

Effect of Sinpo-Tang on the mast cell-mediated anaphylactic reactions.

The herbal formulation Sinpo-Tang (SPT) has long been used for various allergic diseases. We investigated the effect of SPT on the mast cell-mediated anaphylactic reactions in vivo and in vitro murine models. SPT dose dependently inhibited compound 48/80-induced ear swelling response and histamine release. SPT (0.001-0.1g/kg) significantly inhibited passive cutaneous anaphylaxis (PCA). The mast cell number was markedly decreased at the SPT-treated PCA site. In addition, SPT decreased intracellular calcium levels of activated mast cells. These results suggest that SPT inhibit the anaphylactic degranulation of mast cells through decrease of the intracellular calcium level.     

Salviae radix root extract inhibits immunoglobulin E-mediated allergic reaction.

We investigated the effects of the aqueous extract of Salviae radix root (SRRAE) on immediate allergic reactions. SRRAE inhibited by 72.7% passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) immunoglobulin E (IgE). SRRAE dose dependently inhibited histamine release and tumor necrosis factor-alpha production from the rat peritoneal mast cells (RPMCs) by anti-DNP IgE. However, SRRAE showed no significant inhibitory effect on compound 48/80-induced systemic allergic reaction and histamine release from RPMCs. The level of cAMP in RPMCs, when SRRAE was added, significantly increased compared with that of a normal control. These results indicate that SRRAE may contain compounds with actions that inhibit anti-DNP IgE-induced mast cell degranulation in rats.