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     

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.     

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.     

Studies on a new antiallergic pyridinecarboxamide TA-5707F and its sodium salt (TA-5707). II. Mechanism of antiallergic action of TA-5707

Mechanism of the antiallergic action of 6-methyl-N-(1H-tetrazol-5-yl)-2-pyridinecarboxamide (TA-5707F) was studied using the water-soluble sodium salt (TA-5707). 1) TA-5707 administered p.o. at the dose ca. 3 times the ID50 for the PCA reaction did not inhibit capillary dye leakage induced on the rat skin by intracutaneous injection of histamine, serotonin, bradykinin and leukotriene D4 (LTD4). 2) TA-5707, at concentrations above 10(-7) M, inhibited antigen-induced histamine release and dye leakage in the rat peritoneal cavity (passive peritoneal anaphylaxis). 3) TA-5707 inhibited both anaphylactic and compound 48/80-induced histamine release from the rat peritoneal mast cells, the IC50 being ca. 10(-5) M in both cases. It was concluded that TA-5707F exerts its antiallergic action by inhibiting the release of chemical mediators from sensitized cells.     

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.     

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.     

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.     

The pharmacological properties of a new anti-allergic agent, KP-136, in cutaneous models

The pharmacological properties of KP-136 were studied using cutaneous reactions in rats and guinea pigs. KP-136 remarkably inhibited the passive cutaneous anaphylaxis (PCA) with intravenous and oral dosing. However, the inhibitory effect of KP-136 had an apparent species difference. Thus, KP-136 was more effective on rat PCA than that of guinea pig. In four rat cutaneous reactions produced by three allergic reactions and compound 48/80, KP-136 was remarkably effective on two homologous PCA induced by IgE and IgGa. The intravenous and oral doses for 50% inhibition on the PCA were 0.2 mg/kg to 0.4 mg/kg and 0.5 mg/kg to 0.9 mg/kg, respectively. KP-136 was scarcely effective on cutaneous reactions elicited by intradermal injection of histamine and serotonin which are main chemical mediators in rat homologous PCA. However, KP-136 blocked the degranulation of mast cells and decrease of histamine content in skin elicited by the PCA. In addition, KP-136 showed a potent inhibition on the immunological release of histamine from rat peritoneal exudate cells. The concentration for 50% inhibition on the histamine release was 5 ng/ml. These findings indicate that KP-136 is an oral potent inhibitor on PCA, and it acts by blocking the release of chemical mediator(s) from mast cells.     

Antiallergic properties of an orally effective agent, [[3-(1H-tetrazol-5-yl)-phenyl] amino] oxoacetic acid n-butyl ester

A newly synthesized compound, [[3-(1H-tetrazol-5-yl)-phenyl] amino]oxoacetic acid n-butyl ester (MTB) has been demonstrated to be an orally active antiallergic agent. This compound inhibited the 48-hr passive cutaneous anaphylaxis (48-hr PCA) induced by IgE in rats. In guinea pigs, MTB also inhibited the 8-day passive cutaneous anaphylaxis (8-day PCA) and the 8-day passive systemic anaphylaxis induced by IgE. The compound partially inhibited the IgG-mediated 3-hr PCA in rats and guinea pigs, but failed to have any effect on the rabbit IgG-mediated 3-hr PCA in these animals. In the rat, MTB was not an antagonist of histamine or serotonin. The antiallergic effect of MTB was not mediated via any adrenergic mechanisms. MTB significantly inhibited histamine release from rat peritoneal cells induced by rat IgE in vitro.     

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.     

Inhibition of experimental allergic rhinitis by the n-butanol fraction from the anomalous fruits of Gleditsia sinensis

This study was conducted to clarify the effect of the n-butanol fraction from the anomalous fruits of Gleditsia sinensis LAM. (NBGS) on experimental allergic rhinitis. NBGS (100, 200, 400 mg/kg, p.o.) dose-dependently inhibited nasal symptoms (sneezing and nasal rubbing) and dye leakage induced by antigen challenge into the nasal cavity of actively sensitized rats. Significant effects were observed at doses of 200 and 400 mg/kg. NBGS (200, 400 mg/kg) also showed a clear inhibition of sneezing and an inhibitory tendency on nasal rubbing induced by histamine in normal rats. At 400 mg/kg, it significantly reduced dye leakage induced by histamine into the nasal cavity of rats. Terfenadine (10 mg/kg, p.o.), an antihistaminic drug, clearly inhibited the nasal symptoms and the amount of dye leakage induced by antigen or histamine. Furthermore, NBGS significantly reduced in vitro histamine release from rat peritoneal mast cells triggered by compound 48/80 at concentrations of 30 and 100 microg/ml. These results suggest that NBGS may be clinically effective in alleviating the nasal symptoms of allergic rhinitis, probably by inhibiting both histamine release from mast cells and nasal vascular permeability.     

A comparison of the antianaphylactic activities of salbutamol and disodium cromoglycate in the rat, the rat mast cell and in human lung tissue

1 Salbutamol and disodium cromoglycate were compared for anti-anaphylactic activity against passive anaphylaxis in rat skin and peritoneum in vivo and in rat mast cells and human lung fragments in vitro.

2 Salbutamol administered intravenously to rats inhibited cutaneous anaphylaxis, but also inhibited cutaneous responses to histamine and 5-hydroxytryptamine. Salbutamol administered intraperitoneally inhibited the release of slow reacting substance of anaphylaxis (SRS-A) but not the release of histamine in the peritoneum. It was a very weak inhibitor of histamine release from rat mast cells in vitro.

3 Disodium cromoglycate administered intravenously to rats inhibited cutaneous anaphylaxis. Disodium cromoglycate administered intraperitoneally to rats inhibited the release of histamine and, to a lesser extent, SRS-A in the peritoneum. It was an effective but short-acting inhibitor of histamine release from rat mast cells in vitro.

4 Salbutamol was a potent inhibitor of the anaphylactic release of histamine and SRS-A from fragments of human lung.

5 Disodium cromoglycate was a weak inhibitor of the anaphylactic release of histamine and SRS-A from fragments of human lung. The inhibition was variable and not dose-related.

6 The concentration of salbutamol required to inhibit anaphylaxis in human lung is of the same order as that required to relax human bronchial muscle. It is suggested that salbutamol may be more effective in allergic asthma if given in a prophylactic regimen.

     

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.     

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.     

Ixeris dentata green sap inhibits both compound 48/80-induced aanaphylaxis-like response and IgE-mediated anaphylactic response in murine model

We studied the inhibitory effect of the green sap of Ixeris dentata (IXD) on compound 48/80-induced anaphylaxis-like response in a murine model. IXD dose-dependently inhibited the anaphylaxis-like response induced by compound 48/80 in mice. IXD inhibited the anaphylaxis-like fatal response at the dose of 0.1 g/kg by 75%. IXD had a significant inhibitory effect on compound 48/80-induced ear swelling response at the doses of 0.05 and 0.1 g/kg. IXD (0.1 g/kg) also inhibited passive cutaneous anaphylaxis mediated by anti-dinitrophenyl IgE by 81.45%. When IXD was given as a pretreatment at concentrations ranging from 0.005 to 0.1 g/l, the histamine release from rat peritoneal mast cells induced by compound 48/80 was reduced in a dose-dependent manner. These results indicate that IXD may possess antianaphylactic activity.     

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 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.     

Enhancing effect of chlorinated organic solvents on histamine release and inflammatory mediator production

We investigated the effect of several chlorinated organic solvents on antigen-induced histamine release and inflammatory mediator production. Non-purified rat peritoneal mast cells (NPMC) and rat basophilic leukemia (RBL-2H3) cells were sensitized with anti-dinitrophenol (DNP) monoclonal IgE antibody, and then stimulated with DNP-conjugated bovine serum albumin (DNP-BSA) and several chlorinated organic solvents. Trichloroethylene (TCE) and tetrachloroethylene (PCE) enhanced histamine release from antigen-stimulated NPMC and RBL-2H3 in a dose-dependent manner. In addition, TCE and PCE increased IL-4 and TNF-alpha production from antigen-stimulated RBL-2H3. In an in vivo study, we investigated the effect of TCE and PCE on passive cutaneous anaphylaxis (PCA) reaction. TCE and PCE enhanced PCA reaction markedly. These results suggest that TCE and PCE increase histamine release and inflammatory mediator production from antigen-stimulated mast cells via the modulation of immune responses. In addition, exposure to TCE and PCE may lead to the augmentation of allergic diseases.     

Effect of (+/-)-2-[p-(2-thenoyl)phenyl] propionic acid (suprofen) on experimental allergic reactions

The effects of (+/-)-2-[p-(2-thenoyl)phenyl] propionic acid (suprofen), a new anti-inflammatory agent, on experimental allergic reaction and antibody formation were examined. The action was compared with those of ketoprofen, ibuprofen, indomethacin, tranilast, chlorpheniramine, prednisolone and/or cyclophosphamide. Suprofen inhibited homologous PCA in rats, immunological histamine release from rat peritoneal mast cells and guinea pig lung tissues, Forssman cutaneous vasculitis (FCV) and the Arthus reaction in guinea pigs. The potency for inhibition of the PCA reaction was similar to that of ketoprofen and more potent than ibuprofen and trailast. As for the release of anaphylactic mediators, suprofen was less potent than tranilast in terms of histamine release, but not the release of the slow reacting substance of anaphylaxis (SRS-A). Suprofen inhibited FCA more potently than other nonsteroidal anti-inflammatory drugs (NSAID). The inhibition of the Arthus reaction by suprofen was similar to those of other NSAID and prednisolone. Suprofen hardly affected delayed hypersensitivity in guinea pigs and antibody (IgM or IgE) formation in mice or rats.