Inhibition of immunologic and nonimmunologic stimulation-mediated anaphylactic reactions by the aqueous extract of Mentha arvensis

The effect of aqueous extract of Mentha arvensis L. var. piperascens Malinv. (Labiatae) (MAAE) on immunologic and nonimmunologic stimulation-mediated anaphylactic reactions was studied. Nonimmunologic anaphylactic reaction was induced by compound 48/80 injection. MAAE (0.005 to 0.5 g/kg) inhibited systemic anaphylactic reaction induced by compound 48/80. Immunologic anaphylactic reaction was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. MAAE (0.001 to 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) when intraperitoneally, intraveneously and orally administered. MAAE (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. Moreover, MAAE (0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis factor-alpha (TNF-alpha) production. These results indicate that MAAE inhibits immunologic and nonimmunologic stimulation-mediated anaphylactic reactions and TNF-alpha production from RPMC.     

Inhibition of Immunologic and Nonimmunologic Stimulation-Mediated Anaphylactic Reactions by the Aqueous Extract of Mentha arvensis

The effect of aqueous extract of Mentha arvensis L. var. piperascens Malinv. (Labiatae) (MAAE) on immunologic and nonimmunologic stimulation-mediated anaphylactic reactions was studied. Nonimmunologic anaphylactic reaction was induced by compound 48/80 injection. MAAE (0.005 to 0.5 g/kg) inhibited systemic anaphylactic reaction induced by compound 48/80. Immunologic anaphylactic reaction was generated by sensitizing the skin with anti-dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. MAAE (0.001 to 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) when intraperitoneally, intraveneously and orally administered. MAAE (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. Moreover, MAAE (0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis factor-α (TNF-α) production. These results indicate that MAAE inhibits immunologic and nonimmunologic stimulation-mediated anaphylactic reactions and TNF-α production from RPMC.     

Effect of topical application of Brazilian propolis on scratching behavior induced by compound 48/80 in mice

Background and aim: We investigated the effect of topical application of Brazilian propolis on scratching behavior induced by compound 48/80 in mice.

Results: Propolis inhibited compound 48/80-induced scratching behavior when applied immediately after treatment with propolis at a dose of 3?mg/site. Dibucaine 0.3?mg/site also significantly inhibited compound 48/80-induced scratching behavior immediately after application. On the other hand, propolis inhibited compound 48/80-induced scratching behavior even 15, 30 and 60?min after application; however, dibucaine showed no significant inhibition of compound 48/80-induced scratching behavior 15, 30 and 60?min after application. In addition, propolis had no effect on increased vascular permeability just after application, but the drug had a significant effect 15, 30 and 60?min after application. On the contrary, histamine-induced scratching behavior was inhibited significantly by propolis just after application. On the other hand, propolis significantly inhibited histamine release from rat mast cells induced by compound 48/80 at a concentration of more than 10?μg/ml.

Conclusion: From these results, it can be concluded that inhibition of scratching behavior induced by topical application occurred by both its local anesthetic and systemic action through inhibition of histamine release.     

Effects of ICI204,448, naloxone methiodide and levocetirizine on the scratching behavior induced by a κ-opioid antagonist,nor-BNI,in ICR mice

Objective: In this study, we aimed to study the effects of ICI204,448, naloxone methiodide and levocetirizine on the scratching behavior induced by intradermal injection of a ?-opioid antagonist, nor-binaltorphimine (nor-BNI), into the rostral back of ICR mice were investigated.

Materials and methods: Male ICR mice weighing 30?35 g were used. The number of scratching episodes were counted for 60 min after i.d. injection of nor-BNI.

Results: nor-BNI dose dependently increased in the number of scratching episodes in ICR mice. nor-BNI-induced scratching behavior was inhibited by not only nalfurafine but also ICI204,448, a peripherally selective ?-opioid agonist. Naloxone and naloxone methiodide, a peripherally restricted ?-opioid antagonist, also inhibited nor-BNI-induced scratching behavior. Scratching behavior induced by nor-BNI was inhibited by chlorpheniramine as well as levocetirizine, a third-generation H₁ antagonist that does not cross into the CNS.

Conclusion: These results suggest that scratching behavior induced by this ?-opioid antagonist, nor-BNI, is related to not only central but also peripheral opioid and H₁ receptors.     

Effects of Anemarrhena asphodeloides on IgE-mediated passive cutaneous anaphylaxis,compound 48/80-induced systemic anaphylaxis and mast cell activation

BackgroundWe investigated the effect of Anemarrhena asphodeloides Bunge (Liliaceae) water extract (AAWE) on mast cell-mediated anaphylactic reactions. Mast cell-mediated anaphylactic reaction is involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, AAWE is known to have antioxidant and anticancer activity. However, its specific effect on mast cell-mediated anaphylactic reactions is still unknown.MethodsWe examined whether or not AAWE could inhibit IgE-mediated passive cutaneous anaphylaxis (PCA), compound 48/80-induced systemic anaphylaxis, and mast cell activation.ResultsOral administration of AAWE inhibited compound 48/80-induced systemic anaphylaxis in mice. AAWE also inhibited the local allergic reaction, PCA, activated by anti-dinitrophenyl IgE antibody in rats. AAWE reduced compound 48/80-induced degranulation of rat peritoneal mast cells (RPMCs). Moreover, AAWE inhibited histamine release and calcium uptake of RPMCs induced by compound 48/80 in a dose-dependent manner. AAWE also significantly inhibited secretion of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in phorbol 12-myristate 13-acetate plus calcium ionophores A23187-stimulated RPMCs.ConclusionsThese results suggest that AAWE suppresses compound 48/80-induced mast cell activation by inhibition of cellular mechanisms in signaling pathways, and would be beneficial for treatment of mast cell-mediated anaphylactic response.     

Plasma extravasation induced by dietary supplemented histamine in histamine-free mice

Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC-/- mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC+/+ mice but no extravasation in HDC-/- mice. Interestingly, orally administered histamine was distributed in the skin in HDC-/- mice and in these histamine-supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow-derived mast cells of HDC-/- mice took up histamine from the histamine-supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate-type response, the delayed-type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC+/+ and HDC-/- mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate-type allergy model.     

Inhibition of immediate-type allergic reactions by Prunella vulgaris in a murine model.

We studied the effect of aqueous extract of Prunella vulgaris (Labiatae) (PVAE) on immediate-type allergic reactions. PVAE (0.005 to 1 g/kg) dose-dependently inhibited systemic anaphylactic shock induced by compound 48/ 80 in rats. When PVAE was given as pretreatment, at concentrations ranging from 0.005 to 1 g/kg, the serum histamine levels induced by compound 48/ 80 were reduced in a dose-dependent manner. PVAE (0.001 to 1 g/kg) inhibited the passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody dose dependently. PVAE also inhibited the histamine release induced by compound 48/80 or anti-DNP IgE from the rat peritoneal mast cells (RPMC). The level of cyclic AMP in RPMC, when PVAE was added, significantly increased, compared with that of normal control. Moreover, PVAE (0.01 and 0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis factor-alpha production from RPMC. These results indicate that PVAE inhibits immediate-type allergic reactions in rats.     

Bee venom ameliorates compound 48/80-induced atopic dermatitis-related symptoms

Honeybee (Apis mellifera L.) venom (BV) has been traditionally used for the treatment of pain and inflammatory diseases such as itchy skin problems. However, the precise mechanism of BV in ameliorating the scratching behavior is not fully understood. Objective: In order to evaluate the effect of BV on atopic dermatitis-related symptoms in mice, we used a mouse skin scratching model induced by compound 48/80. The anti-itch effect of BV was investigated in a compound 48/80-induced mouse scratching behavior model. BALB/c mice were injected intraperitoneally with vehicle (saline 0.9%) or BV (0.01 and 0.1 mg/kg). One hour after treatment, the animals received a subcutaneous injection of compound 48/80. Intraperitoneal administration of BV (0.01 and 0.1 mg/kg) attenuated compound 48/80-induced scratching behaviors. The anti-scratching behavior effect of BV was in proportional to its vascular permeability effects. Treatment with BV also inhibited the degranulation of mast cells and the production of pro-inflammatory cytokines in compound 48/80-treated skin tissues. According to these results, BV may improve atopic dermatitis-related symptoms by inhibiting the mast cell degranulation and pro-inflammatory cytokine expression.     

Comparison of mouse strain skin sensitivities to anaphylactic mediators and susceptibility to passive cutaneous anaphylactic reactions.

CFW, ICR, and C57Bl/6J mouse strains were examined and compared for their levels of skin sensitivity to histamine and mellitin (a potent mast cell degranulator) and for their susceptibilities to immunoglobulin E-induced passive cutaneous anaphylactic (PCA) reactions. ICR mice were found to exhibit the highest level of sensitivity to histamine and mellitin, whereas C57Bl/6J exhibited the least. CFW mice proved to be the best PCA recipients, whereas ICR mice were the poorest. On the basis of this evidence, no direct correlation is indicated between level of sensitivity to anaphylactic mediators and degree of susceptibility to immunoglobulin E-induced PCA reactions.     

INHIBITION OF IMMEDIATE-TYPE ALLERGIC REACTIONS BY PRUNELLA VULGARIS IN A MURINE MODEL

We studied the effect of aqueous extract of Prunella vulgaris (Labiatae) (PVAE) on immediate-type allergic reactions. PVAE (0.005 to 1 g/kg) dose-dependently inhibited systemic anaphylactic shock induced by compound 48/80 in rats. When PVAE was given as pretreatment, at concentrations ranging from 0.005 to 1 g/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. PVAE (0.001 to 1 g/kg) inhibited the passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody dose dependently. PVAE also inhibited the histamine release induced by compound 48/80 or anti-DNP IgE from the rat peritoneal mast cells (RPMC). The level of cyclic AMP in RPMC, when PVAE was added, significantly increased, compared with that of normal control. Moreover, PVAE (0.01 and 0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-mediated tumor necrosis factor-α production from RPMC. These results indicate that PVAE inhibits immediate-type allergic reactions in rats.     

Isodon japonicus decreases immediate-type allergic reaction and tumor necrosis factor-alpha production

BACKGROUND: The immediate-type allergic reaction is involved in many allergic diseases such as asthma, allergic rhinitis and sinusitis. The discovery of drugs for the treatment of immediate-type allergic disease is a very important subject in human health. Isodon japonicus Hara (Labiatae) (IJAE) has been used for centuries as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of IJAE on the immediate-type allergic reaction and studied its possible mechanisms of action, focusing on the mast cell-mediated allergic reaction. METHODS: IJAE extracts were anally administered to mice for high and fast absorption. Compound 48/80-induced mortality and compound 48/80- or immunoglobulin E (IgE)-induced histamine release were measured to evaluate the antiallergic effects of IJAE. The effect of IJAE on the model of local allergic reaction in vivo, passive cutaneous anaphylaxis (PCA), was investigated. The production of tumor necrosis factor-alpha (TNF-alpha) was measured by Western blotting. RESULTS: IJAE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. IJAE decreased the PCA reaction activated by anti-dinitrophenyl (DNP) IgE antibody. IJAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, IJAE decreased the production of TNF-alpha in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated human mast cells. CONCLUSION: Our findings provide evidence that IJAE inhibits mast cell-derived immediate-type allergic reactions, and also demonstrate the involvement of TNF-alpha in these effects. We propose the clinical use of IJAE in mast cell-mediated immediate-type allergic diseases.     

Modulation of humoral immune responses by endogenous opioids

The effects of opioid agonists and antagonists were investigated on humoral immune mechanisms in mice and rats. Opioid agonists like morphine, Leu-enkephalin, and Met-enkephalin, enhanced antigen-induced histamine release from mixed peritoneal cells of rats in vitro; this enhancement was effectively antagonized by naloxone, an opioid antagonist. Naloxone, per se, decreased anaphylactic mortality in doses of 10 mg/kg, while it increased mortality in a dose of 1 mg/kg. Reduced IgE antibody titer, measured by passive cutaneous anaphylaxis, decreased hemagglutination titer to sheep red blood cells, blocked histamine release from mixed peritoneal cells of rats in vitro induced by antigen, but had no significant effect when histamine release was induced by compound 48/80. Thus, it appears that endogenous opioids are involved in humoral immune responses.     

Effect of Terbutaline, a β2-adrenergic Receptor Stimulating Compound, on Cutaneous Responses to Histamine, Allergen, Compound 48/80, and Trypsin

The beta-adrenoceptor stimulating agent terbutaline (2 ng-2 microgram) injected intradermally in eight atopic subjects produced a dose-dependent inhibition of the skin reactions induced by subsequently injected allergen. After injection of 0.5 microgram terbutaline inhibition of the flare and weal responses was demonstrable throughout the observation period of 90 min. The flare response induced by histamine, the histamine liberator compound 48/80 and the proteolytic enzyme trypsin was not inhibited by terbutaline in the doses used, suggesting a selective action of terbutaline on the allergen-induced response. The weal response elicited by histamine and compound 48/80 was slightly reduced by 2 microgram terbutaline. It is suggested that pretreatment of the skin with terbutaline interferes with the ability of the cutaneous mast cells to respond to challenge with allergen and that terbutaline produces this effect in doses lower than those needed to counteract the permeability increasing effect of released mediator substances.     

Inhibition of passive cutaneous anaphylaxis by several histamine (H1) and serotonin antagonists in the rat

Drugs of the pizotifen type (pizotifen, cyproheptadine), possessing high H₁-antihistamine and high antiserotonin activities in animal expreiments, exert potent inhibitory actions on the passive cutaneous anaphylaxis (PCA) reaction in the rat. The drug pipethiadene, a 4,9-dihydrothieno(2,3-c)-2-benzothiepin derivative also belongs to this group.Selective histamine H₁-antagonists alone are unable to cause pronounced reduction of the intensity of the PCA reaction in the rat, but in local reactions induced in rats by compound 48/80, histamine H₁-receptors seem to play major role.     

Inhibition of vascular permeability increase in mice. An additional anti-allergic mechanism of glucocorticoids

Effects of glucocorticoids on IgE antibody-mediated 48-hour homologous passive cutaneous anaphylaxis (PCA) and skin reactions caused by mediator releasers and vascular permeability increasing factors were investigated comparatively. Both PCA and skin reactions were evoked in the mouse ear and these reactions were quantitatively evaluated by measuring the amount of dye extravasated into the ear. The glucocorticoids hydrocortisone, prednisolone and dexamethasone inhibited the PCA significantly. The maximum inhibitory effects of these glucocorticoids were obtained when administered 8 h prior to the antigenic challenge. Dexamethasone significantly inhibited the skin reactions caused by compound 48/80, Ca ionophore A 23187 and hypotonic salt solution. Dexamethasone also significantly inhibited the skin reactions caused by histamine, serotonin, platelet-activating factor, leukotrienes C4 and D4, and bradykinin. The maximum inhibitory effects of dexamethasone on these skin reactions were observed when administered 12-6 h before. These results support the previous observations that glucocorticoids inhibit the increase of vascular permeability caused by various stimuli, and indicate that the inhibition of vascular permeability increase contributes at least in part to the inhibitory effects on the PCA and the mediator releaser-induced skin reactions. Furthermore, the inhibition of vascular permeability increase by glucocorticoids might play an important role in their anti-allergic actions.     

Stachys riederi inhibits mast cell-mediated acute and chronic allergic reactions

The effect of aqueous extract of Stachys riederi var. japonica Miq. (Labiatae) (SRAE) on the mast cell-mediated allergic and inflammatory reactions were investigated. SRAE inhibited systemic allergic reaction induced by compound 48/80. SRAE dose-dependently inhibited passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE. SRAE also dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. Moreover, SRAE inhibited the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated human mast cells (HMC-1 cells). These results provide evidences that SRAE may be beneficial in the treatment of acute and chronic allergic diseases.     

Artemisia iwayomogi inhibits immediate-type allergic reaction and inflammatory cytokine secretion

The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. The discovery of drugs for the treatment of immediate-type allergic diseases is a very important subject in human health. In this study, we investigated the effect of Artemisia iwayomogi (AIAE) on mast cell-mediated allergic reaction and inflammatory cytokine secretion. AIAE inhibited compound 48/80-induced systemic reactions in mice. AIAE decreased the passive cutaneous anaphylaxis (PCA) reaction activated by antidinitrophenyl (anti-DNP) IgE antibody. AIAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, AIAE attenuated the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 secretion in human mast cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.     

Artemisia iwayomogi Inhibits Immediate-Type Allergic Reaction and Inflammatory Cytokine Secretion

The immediate-type allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. The discovery of drugs for the treatment of immediate-type allergic diseases is a very important subject in human health. In this study, we investigated the effect of Artemisia iwayomogi (AIAE) on mast cell-mediated allergic reaction and inflammatory cytokine secretion. AIAE inhibited compound 48/80-induced systemic reactions in mice. AIAE decreased the passive cutaneous anaphylaxis (PCA) reaction activated by antidinitrophenyl (anti-DNP) IgE antibody. AIAE dose-dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE. Furthermore, AIAE attenuated the phorbol 12‐myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor-α and interleukin-6 secretion in human mast cells. These results provide evidence that AIAE may be beneficial in the treatment of allergic diseases.     

Anti-allergic effects of Sanguisorba officinalis on animal models of allergic reactions

We investigated the effect of aqueous extract of Sanguisorba officinalis L.(Rosaceae) root (SOAE) on the immediate-type allergic reactions in vivo and in vitro. SOAE (0.01 to 1 g/kg) inhibited systemic allergic reaction induced by compound 48/80. When SOAE was employed in a systemic allergic reaction test, the plasma histamine levels were reduced in a dose-dependent manner. SOAE (0.001 to 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE. SOAE (0.001 to 1 mg/mL) also 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 (cAMP) in RPMC, When SOAE was added, significantly increased compared with that of normal control. Moreover, SOAE (0.01 to 1 mg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production. These results suggest that SOAE may be beneficial in the regulation of immediate-type allergic reaction.     

Effect of leaves of Eriobotrya japonica on anaphylactic allergic reaction and production of tumor necrosis factor-α

Leaves of Eriobotrya japonica Lindl. (Rosaceae) (LEJL) have been used as traditional medicines for inflammatory diseases and chronic bronchitis. However, its effect on mast cell-mediated anaphylactic reaction is not known. The anaphylactic allergic reaction is involved in many allergic diseases such as asthma and allergic rhinitis. In this report, we investigate the effect of LEJL on the anaphylactic allergic reaction and studied its possible mechanisms of action. LEJL inhibited compound 48/80-induced systemic anaphylactic reactions and serum histamine release in mice. LEJL dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis and histamine release from mast cells. Furthermore, LEJL decreased the production of tumor necrosis factor-α in phorbol 12-myristate 13-acetate and A23187-stimulated human mast cells. These findings provide evidence that LEJL could be a candidate as an anti-allergic agent.