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.     

Anti-allergic effects of Teucrium japonicum on mast cell-mediated allergy model

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 Teucrium japonicum Houttuyn (Labiatae) (AXTJ) on the mast cell-mediated allergy model and studied its possible mechanisms of action. AXTJ inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. AXTJ decreased immunoglobulin E-mediated passive cutaneous anaphylaxis reaction. AXTJ reduced histamine release and intracellular calcium from rat peritoneal mast cells activated by compound 48/80. In addition, AXTJ attenuated activation of nuclear factor (NF)-κB, and downstream tumor necrosis factor (TNF)-α expression in phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cells. Our findings provide evidence that AXTJ inhibits mast cell-derived allergic reactions and involvement of intracellular calcium, TNF-α, and NF-κB in these effects.     

Anti-allergic effects of Lycopus lucidus on mast cell-mediated allergy model

The current study characterizes the mechanism by which the aqueous extract of Lycopus lucidus Turcz. (Labiatae) (LAE) decreases mast cell-mediated immediate-type allergic reaction. The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. LAE has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. LAE was anally administered to mice for high and fast absorption. LAE inhibited compound 48/80-induced systemic reactions in mice. LAE decreased the local allergic reaction, passive cutaneous anaphylaxis, activated by anti-dinitrophenyl (DNP) IgE antibody. LAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, LAE decreased the secretion of TNF-alpha and IL-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cells. The inhibitory effect of LAE on the pro-inflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) dependent. LAE attenuated PMA plus A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB, and specifically blocked activation of p38 MAPK, but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that LAE inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.     

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.     

The anti-anaphylactic effect of the gall of Rhus javanica is mediated through inhibition of histamine release and inflammatory cytokine secretion

The immediate-type allergic reaction (anaphylaxis) is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. We investigated the effect of the gall of Rhus javanica (GRJ) on the model of the immediate-type allergic reaction, and studied its possible mechanisms. GRJ inhibited compound 48/80-induced systemic reactions in mice. GRJ attenuated immunoglobulin (Ig) E-mediated local allergic reactions. In addition, GRJ dose dependently decreased histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. The decreasing effect of GRJ on the histamine release was mediated by the modulation of cAMP and [Ca2+]i in mast cells. Furthermore, GRJ decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated TNF-alpha and IL-6 secretion in human mast cells. The inhibitory effect of GRJ on the pro-inflammatory cytokine was c-Jun N-terminal kinase and nuclear factor-kappaB dependent. Our findings provide evidence that GRJ inhibits mast cell-derived immediate-type allergic reactions, and suggest the possible mechanisms of action.     

Effects of Clostridium botulinum C2 toxin-induced depolymerisation of actin on degranulation of suspended and attached mast cells

We studied the effects of C. botulinum C2 toxin, which ADP-ribosylates G-actin, on mast cell degranulation. C2 toxin inhibited degranulation of suspended rat peritoneal mast cells induced by compound 48/80 and dinitrophenyl-conjugated bovine serum albumin (DNP-BSA) maximally by about 50 and 90%, respectively. Inhibition by C2 toxin occurred in a time- and concentration-dependent manner. Half-maximal inhibition of DNP-BSA-induced degranulation by C2 toxin occurred at about 0.015 ng/ml, whereas stimulation of mast cells induced by compound 48/80 was half-maximally inhibited at 0.15 ng/ml C2 toxin. C2 toxin also inhibited stimulated [³H]serotonin release from suspended mast cells. Phorbol 12-myristate 13-acetate (PMA)-induced histamine release of suspended mast cells was inhibited by C2 toxin by about 80–90%. C2 toxin had no effect on calcium ionophore A23187-induced histamine release. Toxin treatment of mast cells caused ADP-ribosylation of actin and depolymerisation of F-actin. Attachment of mast cells, which largely increased the diameter of the subcortical actin network, reduced degranulation stimulated by compound 48/80, antigen and calcium ionophore but not by PMA. Opposite to its effect on suspended cells, in adherent mast cells C2 toxin stimulated degranulation by compound 48/80, antigen, and calcium ionophore but not by PMA. The data indicate that mast cell degranulation and responsiveness towards the actin-depolymerising C2 toxin depend largely on mast cell attachment. Received: 7 October 1996 / Accepted: 22 November 1996     

Action of Dracocephalum argunense on mast cell-mediated allergy model

The discovery of drugs for the treatment of allergic disease is an important subject in human health. Stimulation of mast cells starts the process of degranulation resulting in releasing of mediators, such as histamine. In this report, we investigated the effect of aqueous extract of Dracocephalum argunense Fisch. (Labiatae) (DAAE) on the mast cell-mediated allergic response and studied its possible mechanisms of action, focusing on the histamine release and pro-inflammatory cytokine secretion in mast cells. DAAE inhibited compound 48/80-induced systemic reactions and serum histamine release in mice. In addition, DAAE attenuated IgE-mediated skin allergic reaction. DAAE dose-dependently reduced IgE-induced histamine release from mast cells. The level of cAMP was transiently increased by treatment of DAAE. DAAE specifically blocked the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-induced p38 mitogen-activated protein kinase (MAPK) activation. DAAE decreased the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 in mast cells. Our findings provide evidence that DAAE inhibits mast cell derived allergic reactions, and involvement of cAMP for histamine release and p38 MAPK for pro-inflammatory cytokine secretion in these effects.     

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.     

Inhibitory effects of beta-adrenergic stimulants on increased vascular permeability caused by passive cutaneous anaphylaxis, allergic mediators, and mediator releasers in rats

The effects of isoproterenol, salbutamol, theophylline, and forskolin on IgE antibody-mediated homologous passive cutaneous anaphylaxis (PCA) and on skin reactions caused by allergic mediators and mediator releasers were investigated in rats. Isoproterenol and salbutamol dose-dependently inhibited the PCA and skin reactions caused by histamine, serotonin, and leukotriene C4 (LTC4), elicited at the same time in the same rat. These agents also dose-dependently inhibited the skin reactions caused by platelet-activating factor (PAF), leukotriene D4 (LTD4), compound 48/80 (48/80), and calcium ionophore A23187 (A23187). Propranolol overcame the inhibitory effect of isoproterenol on PCA and skin reactions in a dose-dependent manner. Theophylline and forskolin showed similar effects as the beta-adrenergic stimulants. These results indicate that beta-adrenergic stimulants inhibit the increased vascular permeability caused by allergic mediators, and suggest that this activity of beta-adrenergic stimulants might play an important role in their antiallergic actions. Inhibition of increased vascular permeability might be mediated via beta-receptors and may be related to the increase in intracellular cyclic AMP levels.     

Association between perfluorooctanoic acid exposure and degranulation of mast cells in allergic inflammation

Perfluorooctanoic acid (PFOA) has wide applications, including as a raw material for converted paper and packaging products. With the widespread use of PFOA, concerns regarding its potential environmental and health impacts have increased. In spite of the known hepatotoxicity and genotoxicity of PFOA, correlation with PFOA and allergic inflammation is not well known. In this study, the effect of PFOA on the degranulation of mast cells and mast cell‐mediated allergic inflammation in the presence of FcεRI cross‐linking was evaluated. In immunoglobulin (Ig) E‐stimulated mast cells, PFOA increased the release of histamine and β‐hexosaminidase by the up‐regulation of intracellular calcium levels. PFOA enhanced gene expression of several pro‐inflammatory cytokines, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, and IL‐8 by the activation of nuclear factor (NF)‐κB in IgE‐stimulated mast cells. Also, PFOA exacerbated allergic symptoms via hypothermia, and an increase of serum histamine, TNF‐α, IgE and IgG₁ in the ovalbumin‐induced systemic anaphylaxis. The present data indicate that PFOA aggravated FcɛRI‐mediated mast cell degranulation and allergic symptoms. Copyright © 2016 John Wiley & Sons, Ltd.     

Inhibitory effects of Houttuynia cordata water extracts on anaphylactic reaction and mast cell activation

The present study was investigated the effect of Houttuynia cordata THUNB water extract (HCWE) on mast cell-mediated anaphylactic reactions. The mast cell-mediated anaphylactic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. HCWE has been used as a traditional medicine in Korea and is known to have an antioxidant and anti-cancer activities. However, its specific effect of mast cell-mediated anaphylactic reactions is still unknown. We examined whether HCWE could inhibit compound 48/80-induced systemic anaphylaxis, IgE-mediated passive cutaneous anaphylaxis (PCA), and mast cell activation. The oral administration of HCWE inhibited compound 48/80-induced systemic anaphylaxis in mice. HCWE also inhibited the local allergic reaction, PCA, activated by anti-dinitrophenyl (DNP) IgE antibody in rats. HCWE reduced the compound 48/80-induced mast cell degranulation and colchicine-induced deformation of rat peritoneal mast cells (RPMC). Moreover, HCWE dose-dependently inhibited histamine release and calcium uptake of RPMC induced by compound 48/80 or anti-DNP IgE. HCWE increased the level of intracellular cAMP and inhibited significantly the compound 48/80-induced cAMP reduction in RPMC. These results suggest that HCWE may be beneficial in the treatment of mast cell-mediated anaphylactic responses.     

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.     

Angelicae Gigantis Radix regulates mast cell-mediated allergic inflammation in vivo and in vitro

Angelicae Gigantis (AG) Radix, commonly used medicinal food, has been reported as a promising candidate for inflammatory diseases. However, the anti-allergic effects of AG and its molecular mechanisms have yet to be clarified. The present study investigated the anti-allergy effects of ethanol extracts of AG on mast cell-mediated allergic inflammation in vivo and in vitro. The finding of this study demonstrated that AG reduced anti-dinitrophenyl IgE antibody-induced passive cutaneous anaphylaxis, compound 48/80-induced histamine release, 2,4-dinitrofluoro benzene-induced contact hypersensitivity. In addition, AG inhibited the production of interleukin (IL)-6, IL-8, and TNF-α, as well as the activation of Jun N-terminal kinase and nuclear factor-κB in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cells. In conclusion, our results provide a novel insight into the pharmacological actions of AG as a potential candidate for use in allergic inflammatory diseases.     

Characterization of human serotonin 1D and 1B receptors using [ 3H]-GR-125743, a novel radiolabelled serotonin 5HT1D/1B receptor antagonist

Clostridium difficile toxin B that inactivates Rho subfamily proteins by glucosylation, inhibited dinitrophenyl-conjugated bovine serum albumin (DNP-BSA) and phorbol 12-myristate 13-acetate (PMA)-induced mast cell activation by 80 to 90% in a concentration- and time dependent manner with a delay of about 30 min. Activation of mast cells by compound 48/80 and calcium ionophore A23187 was maximally inhibited by about 50%. Inhibition by toxin B was observed with suspended, attached and permeabilised mast cells. C3 ADP-ribosyltransferase, which selectively inactivates RhoA,B,C subtype proteins inhibited antigen, compound 48/80, PMA, A23187 and GTP[S]-induced degranulation of permeabilised mast cells. C3-induced inhibition of stimulated histamine release was smaller than that observed with toxin B and both inhibitory effects were not additive. These findings suggest the involvement of Rho subtype GTPases and, additionally, of other members of the Rho subfamily GTPases in activation of rat peritoneal mast cells. Received: 7 October 1996 / Accepted: 22 November 1996     

Anti-allergic action of buckwheat (Fagopyrum esculentum Moench) grain extract

The anti-allergic action of buckwheat grain extract (BGE) was investigated using rodent experimental models. The oral, intraperitoneal and intradermal administration of BGE significantly inhibited the compound 48/80-induced vascular permeability documented by Evans blue extravasation. In addition, BGE showed potent inhibitory effect on passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE when orally administered. In an in vitro study, BGE revealed to possess inhibitory potential on the compound 48/80-induced histamine release from rat peritoneal mast cells (RPMC). Moreover, BGE inhibited the IL-4 and TNF-alpha mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. Taken together, these results suggest that anti-allergic action of BGE may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.     

Anti-allergic inflammatory activity of the fruit of Prunus persica: Role of calcium and NF-κB

Mast cell-mediated allergic symptoms are involved in many diseases, such as asthma and sinusitis. In this study, we investigated the effect of ethanol extract of fruits of Prunus persica (L) Batsch (FPP) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. FPP dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated local allergic reactions. Histamine releasing from mast cells was reduced by FPP, which was mediated by modulation of intracellular calcium. In addition, FPP attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of FPP on pro-inflammatory cytokines was nuclear factor (NF)-κB dependent. Our findings provide evidence that FPP inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-κB in these effects.     

Selective inhibition by vasocortin of histamine release induced by dextran and concanavalin-A from rat peritoneal cells

Vasocortin, a glucocorticoid-induced anti-inflammatory protein, has been purified from the peritoneal lavage fluid of dexamethasone-treated rats. Vasocortin inhibited the release of histamine from rat peritoneal cells stimulated by dextran or concanavalin A but did not alter the release induced by calcium ionophore A23187 or compound 48/80. This selective effect exhibited by vasocortin mimics the glucocorticoid inhibition of histamine release from rat mast cells.     

Sophora flavescens Aiton inhibits the production of pro-inflammatory cytokines through inhibition of the NF κB/IκB signal pathway in human mast cell line (HMC-1)

The dried roots of Sophora flavescens Aiton (SFA) has been used in traditional medicine for treatment of inflammation, gastrointestinal hemorrhage, diarrhea, and asthma. In the present study, we investigated the effect of SFA on the inflammatory allergic reaction using human mast cell-1 (HMC-1). SFA (200 mg/kg) inhibited the mast cell-mediated passive cutaneous anaphylaxis reaction in vivo and the release of histamine from rat peritoneal mast cells by compound 48/80. In addition, the expression levels of phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-α, IL-6, and IL-8 were also decreased by SFA treatment. In molecular mechanism level, this study showed that SFA inhibited the nuclear translocation of nuclear factor (NF) κB through inhibition of the phosphorylation and degradation of IκB-α, which is an inhibitor of NF κB. Moreover, SFA suppressed PMA plus A23187-induced phosphorylation of the mitogen-activated protein kinase p38 and c-jun N-terminal kinase. The inhibited induction of NF κB promoter by SFA was determined using luciferase activity. These results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.