Magnoliae flos inhibits mast cell-dependent immediate-type allergic reactions.

The mast cell plays a pivotal role in initiating allergic response by secreting intracytoplasmic granular mediators such as histamine. Magnoliae flos has been used for the treatment of allergic disease in Korea. However, its effect in experimental models remains unknown. The present report describes an inhibitory effect of Magnoliae flos on mast cell-mediated immediate-type allergic reactions. Topical application of compound 48/80 can induce an ear swelling response in normal (WBB6F1-+/+) mice but not in the congenic mast cell-deficient WBB6F1-W/Wv mice. Magnoliae flos inhibited concentration-dependently mast cell-dependent ear swelling response induced by compound 48/80 by topical application. Magnoliae flos inhibited concentration-dependently passive cutaneous anaphylaxis induced by anti-dinitrophenyl (DNP) IgE in rats by topical application. Magnoliae flos also inhibited concentration-dependently the histamine release from the rat peritoneal mast cells by compound 48/80 or anti-DNP IgE. Moreover, Magnoliae flos had a significant inhibitory effect on compound 48/80-induced systemic anaphylactic reaction. These results indicate that Magnoliae flos inhibits immediate-type allergic reactions by inhibition of mast cell degranulation in vivo and in vitro.     

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.     

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.     

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.     

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.     

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.     

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.     

Inhibition of anaphylaxis-like reaction and mast cell activation by water extract from the fruiting body of Phellinus linteus

Mast cell-mediated anaphylactic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. Phellinus linteus has been used as a traditional herb medicine in oriental countries and is known to have anti-tumor, immunomodulatory, anti-inflammatory, and anti-allergic activities. However, roles of Phellinus linteus in the mast cell-mediated anaphylactic reactions have not fully been examined. In the present study, we have investigated the effects of water extract from the fruiting body of Phellinus linteus (WEPL) on mast cell-mediated anaphylaxis-like reactions. Oral administration of WEPL inhibited the compound 48/80-induced systemic anaphylaxis-like reaction and ear swelling response. WEPL also inhibited the anti-dinitrophenyl (DNP) IgE-mediated passive systemic and cutaneous anaphylaxis. WEPL had no cytotoxicity on rat peritoneal mast cells (RPMC). WEPL dose-dependently reduced histamine release from RPMC activated by compound 48/80 or anti-DNP IgE. Moreover, WEPL decreased the compound 48/80-induced calcium uptake into RPMC. Furthermore, WEPL increased the level of intracellular cAMP and significantly inhibited the compound 48/80-induced cAMP reduction in RPMC. These results suggest that WEPL may serve as an effective therapeutic agent for allergic diseases.     

Rubus croceacanthus Leveille inhibits mast cell-mediated anaphylactic-like reaction and tumor necrosis factor-alpha secretion

This work aims at examining the effect of the concentrated methanol extract of Rubus croceacanthus Leveille (RCL) on mast cell-mediated anaphylactic-like reaction in a murine model. RCL inhibited compound 48/80-induced systemic anaphylactic-like reaction. When RCL was given as pre-treatment at concentrations ranging from 0.01 to 1 mg/ml, the histamine release from rat peritoneal mast cells induced by compound 48/80 or anti-dinitrophenyl (DNP) immunoglobulin E (IgE) was reduced in a dose-dependent manner. RCL also inhibited passive cutaneous anaphylaxis activated by anti-DNP IgE. In addition, RCL inhibited phorbol 12-myristate 13-acetate and A23187-induced tumor necrosis factor-alpha secretion from human mast cell line HMC-1 cells. These results indicate that RCL may possess a strong anti-anaphylactic 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.     

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.     

ANTIANAPHYLACTIC PROPERTIES OF EUGENOL

The effects of eugenol, a major component of clove, on anaphylaxis were evaluated in rats. Eugenol inhibited compound 48/80-induced systemic anaphylaxis 100% with a dose of 10 μg g⁻¹body weight (BW). While serum levels of histamine were markedly elevated after compound 48/80 injection in all groups of rats, rats injected with eugenol showed a significant reduction in serum histamine levels. Eugenol also inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. Eugenol dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The morphological examination clearly showed that eugenol prevented the anaphylactic degranulation of RPMC. Moreover, Eugenol (10 μg ml⁻¹) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-α production. These results suggest that eugenol has antianaphylactic properties by preventing mast cell degranulation     

Anti-allergic effects of nilotinib on mast cell-mediated anaphylaxis like reactions

Nilotinib is a new orally bioavailable potent tyrosine kinase inhibitor that is used for the treatment of BCR-ABL-positive chronic myelogenous leukemia. However, its effect on mast cell-mediated anaphylactic reaction is still not known. The present study aimed to investigate the effect of nilotinib on the anaphylactic allergic reaction and study its possible mechanism(s) of action. Nilotinib administration prevented systemic anaphylaxis in mice, mediated by compound 48/80, in a dose- and time-dependent manner. Also, nilotinib significantly inhibited (P<0.05) allergic paw edema in rats. Furthermore, nilotinib significantly decreased (P<0.05) the IgE-mediated passive cutaneous anaphylaxis in a dose dependent manner. In addition, nilotinib dose-dependently reduced histamine release from the rat peritoneal mast cells activated either by compound 48/80 or by ovalbumin. Moreover, nilotinib attenuated the secretion of pro-inflammatory cytokine, tumor necrosis factor (TNF)-α expression in the rat peritoneal mast cells. These findings provide evidence that nilotinib inhibits mast cell-derived immediate-type allergic reactions and so it could be a candidate as an anti-allergic agent.     

Inhibition of immunologic and nonimmunologic stimulation-mediated anaphylactic reactions by water extract of white eggplant (Solanum melongena).

We investigated the effect of water extract of Solanum melongena(SMWE) on immunologic and nonimmunologic stimulation-mediated anaphylactic reactions. Nonimmunologic anaphylactic reaction was induced by compound 48/80 injection. Oral administration of SMWE (1 g kg(-1)) completely inhibited compound 48/80-induced anaphylactic reaction. Immunologic anaphylactic reaction was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. Oral administration of SMWE (0.01--1 g kg(-1)) significantly inhibited passive cutaneous anaphylactic reaction activated by anti-DNP IgE to between 83.10 +/- 1.67% and 70.17 +/- 2.17%. SMWE (0.01--1 mg ml(-1)) also inhibited histamine release activated by compound 48/80 to between 93 +/- 2.65 and 70 +/- 1.50%. Moreover, SMWE (0.01--1 mg ml(-1)) had a significant inhibitory effect on IgE-induced tumor necrosis factor (TNF)-alpha secretion from rat peritoneal mast cells. These results indicate that SMWE inhibits immunologic and nonimmunologic stimulation-mediated anaphylactic reactions and TNF-alpha secretion from mast cells.     

Inhibition of immediate allergic reactions by ethanol extract from Plumbago zeylanica stems

The antiallergic properties of the 70% ethanol extract from Plumbago zeylanica stems (EPZ) were investigated in the present study. The extract (500, 1000 mg/kg, p.o.) dose-dependently inhibited systemic anaphylactic shock induced by compound 48/80 in mice, reduced homologous passive cutaneous anaphylaxis and skin reactions induced by histamine or serotonin in rats, significant differences were observed at the dose of 1000 mg/kg. In vitro, EPZ (5, 20, 50 microg/ml) concentration-dependently reduced histamine release from rat peritoneal mast cells caused by compound 48/80 and antigen. EPZ (50 microg/ml) markedly increased intracellular cAMP content of rat mast cells. These findings demonstrate that EPZ inhibits mast cell-dependent immediate allergic reactions, which is probably mediated by reducing the release of mediators such as histamine from mast cells via elevating intracellular cAMP level and weakening the inflammatory action of mediators.     

Anti-allergic components from the peels ofCitrus unshiu

In a bioassay-guided search for anti-allergic compounds from higher plants of Korea, polymethoxyflavones, 3',4',5,6,7,8-hexamethoxyflavone (1), 5-hydroxy-3',4',6,7,8-pentamethoxyflavone (II) and 3',4',5,7,8,-pentamethoxyflavone (III) have been isolated from the immature peels of Citrus unshiu. Structures of these compounds were elucidated on the basis of spectroscopic techniques. Compounds I and II inhibited dose-dependently histamine release from the rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE.     

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.     

The evaluation of the antianaphylactic effect of Oryza sativa L. subsp. hsien Ting in rats.

We studied the effect of the methanol extract of Oryza sativa L. subsp. hsien Ting (OSHT) on anaphylaxis. OSHT (0.001-1.0 mg g-1body weight (BW)) dose-dependently inhibited systemic anaphylaxis induced by compound 48/80 in rats. When OSHT was pretreated at concentrations ranging from 0.001 to 1.0 mg g-1BW, the serum histamine levels were reduced in a dose-dependent manner. OSHT (0. 001-1.0 mg g-1BW) also inhibited local anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. Moreover, OSHT dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cAMP in RPMC, when OSHT was added, significantly increased approx. 20-fold compared with that of basal cells. These results indicate that OSHT possesses strong antianaphylactic activity by inhibition of histamine release from mast cells in vivo and in vitro.     

Inhibitory effects of Morus alba on compound 48/80-induced anaphylactic reactions and anti-chicken gamma globulin IgE- mediated mast cell activation

We investigated the effects of hot-water extract from the root bark of Morus alba (HEMA) on anaphylactic reactions. Using in vitro and in vivo experiments, we examined whether HEMA could inhibit compound 48/80-induced systemic anaphylactic shock and anti-chicken gamma globulin (CGG) IgE-mediated rat peritoneal mast cell activation. HEMA significantly inhibited systemic anaphylaxis induced by the compound 48/80 in mice. HEMA also significantly inhibited the passive cutaneous anaphylaxis activated by anti-CGG IgE. HEMA had no cytotoxicity on rat peritoneal mast cells (RPMC). Moreover, HEMA dose-dependently inhibited mast cell degranulation, histamine release and calcium uptake into RPMC induced by the compound 48/80 or anti-CGG IgE. When HEMA was added, the level of intracellular cAMP in RPMC showed a transient and significant increase (5-fold) compared with that of control cells. HEMA also inhibited significantly the compound 48/80-induced cAMP reduction in RPMC. These results suggested that HEMA inhibits the compound 48/80- or anti-CGG IgE-induced mast cell activation and its inhibitory effects on mast cell activations were favorably comparable to disodium cromoglycate. And HEMA is a candidate for effective therapeutic tools of allergic diseases.     

Characterization of FPL-52694 [5-(2-hydroxypropoxyl)-8-propyl-4-oxo-4H-benzopyran-2-carboxylic acid Na] on histamine release from rat peritoneal mast cells induced by antigen, compound 48/80 and A 23187

We studied the in vitro effects of FPL-52694 [5-(2-hydroxypropoxyl)-8-propyl-4-oxo-4H-benzopyran-2-carboxylic acid Na] on histamine release from rat peritoneal mast cells. These cells exposed to ascaris antigen, compound 48/80 or the ionophore A 23187 concentration-dependently released histamine. About a 30-40% histamine release was obtained by 1 X 10(-4) g/ml of antigen, 1 X 10(-7) g/ml of compound 48/80 and A 23187. FPL-52694 (10(-9)-10(-4) g/ml) concentration-dependently inhibited the histamine release from mast cells in response to antigen (1 X 10(-4) g/ml) and compound 48/80 (1 X 10(-7) g/ml), but only slightly inhibited the histamine release induced by A 23187 (1 X 10(-7) g/ml). Similar results were obtained with disodium cromoglycate (DSCG), in the same dose ranges. However, the inhibitory activity of FPL-52694 on histamine release by antigen and compound 48/80 was approximately 10 times more potent than that of DSCG at certain concentrations. Tachyphylaxis was observed when these two agents were preincubated with mast cells for 10 min. These results show FPL-52694 to be a novel mast cell stabilizer.