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.     

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.     

Antipruritic and antiinflammatory effects of aqueous extract from Si-Wu-Tang

Si-Wu-Tang (SWT), a traditional Chinese formula, has been clinically used in the treatment of cutaneous pruritus, chronic inflammation, and other diseases. The present study was carried out to observe the antipruritic and antiinflammatory effects of SWT aqueous extract using compound 48/80 and picryl chloride (PC) models in mice. SWT (500, 1000 mg/kg p.o.) clearly reduced the scratching responses elicited by compound 48/80 in normal mice. At doses of 250 and 500 mg/kg, it inhibited the scratching responses induced by PC in mice actively sensitized with 2,4-dinitrophenol (DNP)-ovalbumin (OVA) plus alum. Furthermore, SWT (250, 500, 1000 mg/kg) significantly inhibited the footpad swelling caused by compound 48/80 in mice. In the biphasic ear skin reactions induced by PC in actively sensitized mice, SWT (250, 500 mg/kg) reduced the immediate-phase reaction, but did not affect the late-phase reaction. In vitro, SWT (50-500 microg/ml) showed a concentration-dependent inhibition of the histamine release induced by compound 48/80 from rat peritoneal mast cells. The crude drugs contained in SWT, Paeoniae Radix (25, 100 microg/ml), Rehmanniae Radix, and Chuanxiong Rhizoma (100 microg/ml), also showed a clear inhibition, but Angelica Radix did not at the concentrations examined. These findings indicate that SWT aqueous extract has antipruritic and antiinflammatory effects in mice. SWT inhibits histamine release from rat mast cells, and Paeoniae Radix probably plays a crucial role in the formula.     

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.     

Effect of Brazilian propolis on scratching behavior induced by compound 48/80 and histamine in mice

We studied the effect of Brazilian propolis on scratching behavior induced by compound 48/80 and histamine in ICR mice. Propolis granular A.P.C dose-related inhibited scratching behavior induced by compound 48/80 and significant inhibition were observed at 1000 mg/kg. However, histamine-induced scratching behavior was not inhibited by propolis granular A.P.C even at 1000 mg/kg. Propolis ethanol extract at 10 microg/ml or more inhibited histamine release from rat mast cells induced by compound 48/80. In addition, it blocked increased vascular permeability induced by compound 48/80. The inhibitory effect of propolis on scratching behavior induced by compound 48/80 was gradually enhanced by repeated administration, and 500 mg/kg propolis granular A.P.C, which caused no effect through single administration, significantly inhibited scratching behavior after repeated administration for 4 weeks. From these findings, it is assumed that the inhibition of scratching behavior induced by propolis occurs through a mast cell-dependent mechanism.     

Antipruritic and antierythema effects of ascomycete Bulgaria inquinans extract in ICR Mice

The effect of ethanol extract obtained from Bulgaria inquinans on the scratching behavior and vascular permeability changes induced by compound 48/80, histamine and serotonin in ICR mice was studied. The extract dose-dependently inhibited scratching behavior induced by compound 48/80 and serotonin. A significant inhibition was observed at doses of 300 and 600 mg/kg when Bulgaria inquinans extract was administered orally. However, no inhibitory effect was observed on the histamine-induced scratching behavior by the extract, even at a dose of 600 mg/kg. In addition, it also inhibited the increase in the vascular permeability induced by compound 48/80 and serotonin at doses of 300 and 600 mg/kg; however, it failed to inhibit the increased vascular permeability induced by histamine, even at a dose of 600 mg/kg. Bulgaria inquinans extract showed a potent inhibitory effect on histamine release induced by compound 48/80. These results suggest that Bulgaria inquinans extract is effective in cutaneous pruritus and erythema, which were probably mediated by inhibiting the release of histamine from mast cells and antagonizing the effect on serotonin.     

Roles of mast cells and histamine in mosquito bite-induced allergic itch-associated responses in mice.

We investigated itch-associated responses (scratching) to mosquito bites and the role of histamine and mast cells in mosquito-induced itching in mice. Although the first bites of mosquito Aedes albopictus did not increase scratching, repeated bites increased scratching. The response was not diminished even after an interval of 2 months. Similarly, repeated intradermal (i.d.) injections of salivary gland extract (SGE) from Aedes albopictus increased scratching after SGE injection itself and mosquito bites. The scratching peaked within 10 min and almost subsided by 60 min. The opioid antagonist naloxone (1 mg/kg, s.c.) inhibited scratching following SGE injection. Although the non-sedative H1-histamine-receptor antagonist terfenadine (30 mg/kg, p.o.) significantly suppressed scratching induced by histamine (100 nmol/site, i.d.) in either naive or mosquito-sensitized mice, it did not affect mosquito-induced scratching in mosquito-sensitized mice. Repeated injections of SGE increased scratching in mast cell-deficient (WBB6F1-W/Wv) mice as well as in normal (WBB6F1-+/+) littermates. Repeated exposure to mosquito bites roughly doubled serum concentrations of total IgE and IgG1, but not IgG2a. Repeated injections of SGE markedly increased plasma extravasation induced by mosquito bites and such an increase was almost completely suppressed by terfenadine (30 mg/kg, p.o.). The results show the presence of histamine-mediated and histamine-independent mechanisms in cutaneous itching and suggest that histamine probably released from mast cells does not play an important role in itching in immediate allergic reaction. Our murine model of mosquito itching may be useful for studying the mechanisms of immediate allergic itching.     

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 effects of astemizole on immediate type hypersensitivity reactions.

Astemizole (0.5-5 mg/kg, p.o.) dose-dependently inhibited heterologous and homologous PCA reactions in rats at ID50 values of 1.48 mg/kg and 2.37 mg/kg, respectively. The inhibitory effect of astemizole on heterologous PCA was most remarkable when this compound was given p.o. 2 h prior to antigen challenge. Astemizole (0.1-5 mg/kg, p.o.) dose-dependently inhibited experimentally-induced asthma in guinea pigs at an ID50 of 0.86 mg/kg. Ex vivo, astemizole (0.5-5 mg/kg, p.o.) inhibited antigen-induced histamine release from lung pieces of sensitized guinea pigs. In in vitro experiments, the drug dose-dependently inhibited antigen-induced histamine and SRS-A releases from guinea pig lung pieces at concentrations of 0.05-10 microM. Furthermore, astemizole (0.1-10 microM) inhibited the histamine release induced by compound 48/80 and antigen-antibody reaction from rat peritoneal mast cells, and at 0.1-500 nM inhibited both leukotriene C4- and platelet-activating factor (PAF)-induced contraction of isolated guinea pig trachea at submicromolar concentrations. Astemizole not only inhibited 45Ca uptake into rat mast cells but also prevented the Ca2+ release from the intracellular Ca store induced by compound 48/80, although this compound did not affect the histamine release from permeabilized mast cells induced by Ca2+. Our results suggest that one of the antiallergic mechanisms of astemizole may be an inhibition of signal transduction from the mast cell membrane to the intracellular systems.     

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

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

Antinociceptive and antiinflammatory activities of Artemisia copa extracts.

The aqueous extract from aerial parts of Artemisia copa Phil. (Compositae), was evaluated for antinociceptive activity using writhing, formalin, and hot-plate tests in mice. A dose-related antinociceptive response was obtained in the writhing test at doses of 500 and 1000 mg/kg p.o. (percentage of inhibition 23.3 and 52.70, respectively). The extract also inhibited the second phase of formalin test (38.81%) and this effect was not antagonized by pretreatment with naloxone 5mg/kg i.p. Furthermore, no significant effect was obtained in the hot-plate test. Dichloromethane and ethanolic extracts, were analyzed for antiinflammatory activity with the carrageenan-induced paw edema in rats and the ear edema induced by 12-O-tetradecanoylphorbol-13 acetate (TPA) and arachidonic acid (AA) in mice. Both extracts showed antiinflammatory activity in the TPA (88 and 54%), and the ethanolic extract showed a 37% inhibition in AA test. No effects were seen at doses of 300 mg/kg p.o. and 100 mg/kg i.p. in the carrageenan test. The results obtained indicate that A. copa has analgesic and topical antiinflammatory activities that supports the folk medicinal use of the plant.     

Antiallergic effects of 4-[2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy]-bu tyric acid

Antiallergic effects of 4-[2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy]-buty ric acid (C4C) were studied. C4C is an active principal metabolite of an orally effective antiallergic agent, KP-136. C4C (0.2-1 mg/kg, i.v.) markedly inhibited the mast cell-mediated homologous PCA of rats and the experimental allergic asthma of rats and guinea pigs, although it had almost no effects on heterologous PCA and compound 48/80-induced cutaneous response in rats. C4C (0.2 mg/kg, i.v.) was scarcely effective on cutaneous responses induced by intradermal injection of histamine and serotonin which are principal chemical mediators of rat homologous PCA, and it blocked the decrease of skin histamine content after the PCA. In addition, C4C (0.01-0.5 micrograms/ml) inhibited the increase of 45Ca uptake of mast cells, the histamine release and the degranulation induced by the antigen-antibody interaction. These effects of C4C were much the same as those of KP-136. From the above findings, C4C is considered to be an antiallergic agent that inhibits the mast cell activation by blocking the calcium influx, and it shares similar pharmacological properties with KP-136.     

Inhibitory effects of the methanol extract of Ganoderma lucidum on mosquito allergy-induced itch-associated responses in mice

Recently, we showed that a methanol extract of Ganoderma lucidum inhibits scratching, an itch-related response, induced by intradermal injections of some pruritogens in mice. The present study investigated whether G. lucidum extract would inhibit allergic itch. In mice sensitized with an extract of salivary gland of mosquito (ESGM), an intradermal injection of ESGM elicited scratching, which was suppressed by oral administration of G. lucidum extract (100 and 300 mg/kg). The scratching was inhibited by the H? histamine-receptor antagonist azelastine, but not by the peripherally acting H?-antagonist terfenadine, at the oral dose of 30 mg/kg. In sensitized mice, ESGM increased the activity of cutaneous nerve, which was suppressed by G. lucidum extract (300 mg/kg). Although terfenadine (30 mg/kg) inhibited plasma extravasation induced by ESGM in the sensitized mice, G. lucidum extract (300 mg/kg) was without effect. These results suggest that G. lucidum extract relieves allergic itch through a peripheral action. The results support the idea that mast cells and H? histamine receptors are not the primary sites of the antipruritic action of G. lucidum extract.     

Evaluation of the effect of Myrica sapida on bronchoconstriction and bronchial hyperreactivity

The present investigation was undertaken to evaluate the bronchodilator and bronchial hyperreactivity of the stem bark of Myrica sapida. Experimental models studied were histamine induced bronchospasm in guinea pigs, bronchoalveolar lavage fluid (BALF) in egg albumin sensitized guinea pigs, histamine release from the lung tissues of sensitized guinea pigs and histopathological studies. Ethanolic extract of M. sapida (75 mg/kg, p.o., for 7 days) showed significant protection against histamine aerosol induced bronchospasm. Significant decrease in the total and differential leukocyte counts in BALF and prevention of egg albumin induced histamine release from chopped lung tissues of sensitized guinea pigs was observed on chronic administration of ethanolic extract of M. sapida (75 mg/kg, p.o., for 15 days). Histological examination of the section of lung from sensitized guinea pigs treated with ethanolic extract of M. sapida (75 mg/kg, p.o., for 15 days) was comparable to that of the control group. These results suggest that M. sapida possesses not only bronchodilator activity but also decreases bronchial hyperresponsiveness by decreasing the infiltration of inflammatory mediators like eosinophils, neutrophils in BALF and inhibiting histamine release from lungs of sensitized guinea pigs.     

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

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

An experimental evaluation of anticonvulsant activity of Vitex-negundo

Maximal electroshock seizures (MES) in albino rats and pentylenetetarazole (PTZ) induced seizures in albino mice were used to study anticonvulsant activity of Vitex-negundo leaf extract. The ethanolic leaf extract of Vitex-negundo was administered orally in graded doses (250, 500 and 1000 mg/kg p.o) in both the experimental models and the effects were compared with diphenylhydantoin in MES method and valporic acid in PTZ induced seizures method as standard control respectively. The Vitex-negundo in the doses (250, 500 and 1000 mg/kg, p.o) did not show protection against MES to any significant extent but significant post-ictal depression was observed in the dose of 1000 mg/kg body weight in comparison to control. However, sub-protective dose of test drug (100 mg/ kg, p.o) potentiated the anticonvulsant action of diphenylhydantoin. The test drug in the dose (1000 mg/kg, po) showed 50% protection in clonic seizures and 24-hour mortality against PTZ induced seizures. It also decreased number and duration of convulsions significantly. Vitex-negundo potentiated anticonvulsant activity of valporic acid. The anticonvulsant activity of Vitex-negundo has not been found equi-effective with standard drugs. These findings suggest that Vitex-negundo possesses anticonvulsant activity particularly against PTZ induced convulsions. Moreover, the potentiation of diphenylhydantoin and valporic acid by Vitex-negundo indicates that it may be useful as an adjuvant therapy along with standard anticonvulsants and can possibly lower the requirement of diphenylhydantoin and valporic acid.     

Histamine release inhibitory activity of Piper nigrum leaf

Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.     

Effect of Lo Han Kuo (Siraitia grosvenori Swingle) on nasal rubbing and scratching behavior in ICR mice

We studied the effect of Lo Han Kuo (Siraitia grosvenori Swingle) on histamine-induced nasal rubbing and compound 48/80-induced skin scratching behavior in ICR mice. An extract and glycoside (a complex of sweet components) of Lo Han Kuo were used in the study. Both the extract and glycoside caused no significant effect on nasal rubbing or scratching behavior, even at a dose of 1000 mg/kg when administered in a single dose. However, the effect of Lo Han Kuo became clear after repeated administration, and 300 and 1000 mg/kg of both extract and glycoside significantly inhibited nasal rubbing and skin scratching behavior after consecutive treatment for 4 weeks. Both the extract and glycoside inhibited the histamine release induced by compound 48/80 at concentrations of 300 and 1000 microg/ml. From these results, it is assumed that the inhibition of nasal rubbing and skin scratching behavior induced by Lo Han Kuo occurs through a mast cell-dependent mechanism.     

蛇床子素抗变态反应的研究

蛇床子素能较强地抑制小鼠被动皮肤过敏(PCA)反应,对整体豚鼠组胺性喘息具有保护作用,对慢反应物质(SRS-A)引起的豚鼠离体回肠收缩以及豚鼠离体回肠的Schultz-Dzle反应呈明显的拮抗和阻断作用,并能抑制大鼠腹腔肥大细胞脱颗粒。上述作用均呈一定的剂量依赖关系。     

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.