The analgesic and anti-inflammatory effects of 7-oxosandaracopimaric acid isolated from the roots of <Emphasis Type="Italic">Aralia cordata</Emphasis>

The root of Aralia cordata is a traditional medicine for the treatment of inflammation, fever, pain, and spasm in the various diseases in Korea. We isolated a dibenzylbutyrolactone diterpene acid, 7-oxosandaracopimaric acid (OSA), from the ether fraction of Aralia cordata MeOH extract, and studied the effect of OSA on phenylquinone (PQ)-induced writhing syndrome and PQ-induced capillary permeability increase, compound 48/80-induced histamine release by peritoneal mast cells, cycloxygenase (COX) activities, and silica-induced RAW 264.7 cell reactive oxygen species production. OSA (30 mg/kg, p.o.) significantly (p < 0.05) inhibited PQinduced writhes by 25.8% and the PQ-induced capillary permeability increase levels by 33.13% as compared with PQ control. Furthermore, OSA (10 mM) inhibited COX-1 by 22.82 ± 1.94%, and COX-2 by 15.86 ± 1.35%, respectively, to the same extent as indomethacin at the same concentration (10 mM). And OSA (3.0 mM) significantly (p < 0.05) inhibited compound 48/80-induced histamine release from rat mast cells, and its activity was similar to that of celebrex (1 mM), but no piracetam (0.1 mM) inhibited them. OSA did not inhibit ROS production in RAW 264.7 cells. These results indicated that OSA has analgesic and anti-inflammatory effects due to its inhibitory effects on capillary permeability, COX activities, and histamine release.     

Inhibitory effects of Moutan cortex on immediate allergic reactions

The anti-allergic effect of an ethanol extract from Moutan Cortex was evaluated in some animal models. The Moutan Cortex extract (30, 100 mg/kg, i.p.) dose-dependently inhibited systemic anaphylactic shock induced by compound 48/80 in mice. It also inhibited dose-dependently the scratching behavior induced by compound 48/80 or histamine at a dose of 100 mg/kg. An increase in the vascular permeability induced by compound 48/80 or histamine was also inhibited by the Moutan Cortex. In addition, in vitro studies, the Moutan Cortex inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. To investigate the active component of Moutan Cortex extract, it was suspended in water and extracted with EtOAc to yield EtOAc insoluble (A) and soluble (B) fractions. The effect of extract (B) was more potent than that of extract (A) in inhibiting histamine release. From these findings, it seems likely that the Moutan Cortex extract is effective in antagonizing certain pharmacological effects induced by compound 48/80, which is probably mediated by inhibiting the release of histamine from mast cells and antagonizing the effect on histamine. The main active component of Moutan Cortex is considered to be contained in extract (B). In conclusion, Moutan Cortex may be useful for the relief of symptoms of atopic dermatitis and other allergy-related diseases.     

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

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

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.     

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 by calcium antagonists of histamine release and calcium influx of rat mast cells: Difference between induction of histamine release by concanavalin A and compound 48/80

The relation between calcium influx and histamine release from rat mast cells was investigated. When purified mast cells pretreated with a calcium antagonist (MnCl₂ or methoxyverapamil (D-600)) were exposed to concanavalin A or compound 48/80 in Tyrode solution (pH 7.4) at 37°C, the calcium antagonists inhibited the extracellular calcium-dependent component of concanavalin A-induced histamine release. MnCl₂ also inhibited the extracellular calcium-dependent component of compound 48/80-induced histamine release, whereas D-600 did not inhibit the release. D-600 inhibited the ⁴⁵Ca uptake induced by concanavalin A, but did not inhibit the ⁴⁵Ca uptake induced by compound 48/80. It was found that the inhibitory action of calcium antagonists depended on the uptake of extracellular calcium. These observations suggest that concanavalin A and compound 48/80 stimulate different mechanisms of calcium influx. Studies on inactivation of the mechanisms of calcium influx showed that calcium influx into cells activated by concavalin A stopped when concanavalin A was washed out, whereas the influxactivated by compound 48/80 was still operative after compound 48/80 had been washed out.     

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.     

The utilization of adenosine triphosphate in rat mast cells during histamine release induced by anaphylactic reaction and compound 48/80

Summary The ATP content of rat peritoneal mast cells has been studied in relation to histamine release induced by compound 48/80 and antigen-antibody (anaphylactic) reaction in vitro. When the ATP content of actively sensitized mast cells was reduced to different levels by oligomycin, a good correlation was obtained between the ATP levels and the amounts of histamine released by the anaphylactic reaction. A similar linear relation has previously been demonstrated between the ATP levels of mast cells and histamine release induced by compound 48/80. The ATP content of mast cells was also studied at different intervals after the exposure of the cells to antigen or compound 48/80. No significant change in the ATP content was observed in untreated mast cells during the short period when histamine release occurs. If, however, the mast cells were preincubated with oligomycin or 2-deoxyglucose to reduce the rate of ATP synthesis while a large part of the histamine release remained unaffected—a decrease in the ATP content could be demonstrated in close time relation to both anaphylactic and compound 48/80-induced histamine release. The observations indicate an increased utilization of ATP in mast cells during the release process.     

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.     

Anti-asthmatic property and possible mode of activity of an ethanol leaf extract of Polyscias fruticosa

Context: Polyscias fruticosa (L.) Harms (Araliaceae) is used as a traditional remedy for asthma in Ghana.

Objective: The objective of this study is to establish the anti-asthmatic property and a possible mode of activity of an ethanol leaf extract of P. fruticosa (PFE).

Materials and methods: The time (min) for pre-convulsive dyspnea, and time for recovery, after sensitization with 150?μg OVA and induction of bronchospasm with 1% acetylcholine or histamine in normal, and 100, 250, and 500?mg/kg PFE-treated Dunkin Hartley guinea pigs, were recorded. Atropine (0.1?mg), mepyramine (0.1?mg), and PFE (1?mg) effect on a contractile response of 2.0?×?10^?2?μg/ml acetylcholine and 5.8 × 10^?2?μg/ml histamine on the isolated guinea pig ileum was investigated. Cytological and histological studies were conducted using guinea pig peritoneal mast cells and mesenteric cells, respectively, to establish PFE effect on compound 48/80-induced mast cell degranulation.

Results: PFE (100–500?mg/kg) prolonged the onset of pre-convulsive dyspnea by 76.1–180.2% (p?≤?0.01–0.001), and decreased recovery time by 71.9–78.5% (p?≤?0.01–0.001). It also enhanced percentage protection against histamine-induced bronchospasm by 15.8–80.1-fold (p?≤?0.05–0.01), and decreased percentage recovery time 2.5–3.3-fold (p?≤?0.05–0.01). PFE significantly inhibited (60.4?±?8.3%) contractile responses of histamine and produced significant inhibition (56–79%: p?≤?0.001) of mast cell degranulation.

Conclusion: PFE has anti-asthmatic, antihistaminic, and mast cell stabilization effect making it useful in traditional asthma management.     

Arctigenin,a phenylpropanoid dibenzylbutyrolactone lignan,inhibits type I–IV allergic inflammation and pro-inflammatory enzymes

We previously reported that arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan isolated from Forsythia koreana, exhibits anti-inflammatory, antioxidant, and analgesic effects in animal models. In addition, arctigenin inhibited eosinophil peroxidase and activated myeloperoxidase in inflamed tissues. In this study, we tested the effects of arctigenin on type I–IV allergic inflammation and pro-inflammatory enzymes in vitro and in vivo. Arctigenin significantly inhibited the heterologous passive cutaneous anaphylaxis induced by ovalbumin in mice at 15 mg/kg, p.o., and compound 48/80-induced histamine release from rat peritoneal mast cells at 10 μM. Arctigenin (15 mg/kg, p.o.) significantly inhibited reversed cutaneous anaphylaxis. Further, arctigenin (15 mg/kg, p.o.) significantly inhibited the Arthus reaction to sheep’s red blood cells, decreasing the hemolysis titer, the hemagglutination titer, and the plaque-forming cell number for SRBCs. In addition, arctigenin significantly inhibited delayed type hypersensitivity at 15 mg/kg, p.o. and the formation of rosette-forming cells at 45 mg/kg, p.o. Contact dermatitis induced by picrylchloride and dinitrofluorobenzene was significantly (p < 0.05) inhibited by surface treatment with arctigenin (0.3 mg/ear). Furthermore, arctigenin dose-dependently inhibited pro-inflammatory enzymes, such as cyclooxygenase-1 and 2, 5-lipoxygenase, phospholipase A2, and phosphodiesterase. Our results show that arctigenin significantly inhibited B- and T-cell mediated allergic inflammation as well as pro-inflammatory enzymes.     

Cyclic AMP independent inhibition by papaverine of histamine release induced by compound 48/80.

Compound 48/80-induced histamine release from isolated rat peritoneal mast cells was inhibited in a dose-dependent manner by papaverine (ic₅₀ approx 20 μM). This effect of papaverine was not influenced by PGE₁ (14–140 μM), even though PGE₁ markedly increased must cell cAMP levels. Papaverine (0.5 mM) completely inhibited histamine release without causing any change in cAMP levels. Theophylline (0.1 and 0.5 mM) potentiated histamine release induced by submaximal concentrations of compound 48/80, while cAMP levels were increased. IBM X was as potent as papaverine in causing inhibition of mast cell phosphodiesterase. IBM X (0.14–0.7 mM) had no effect on histamine release but caused a 6–20 fold increase in mast cell cyclic AMP. Papaverine inhibition of histamine release was gradual at the onset and was parallelled by a depletion of mast cell ATP content. The inhibition of 48/80-induced histamine release and depletion of mast cell ATP levels was reversed by glucose. It is concluded that papaverine induced inhibition of 48/80-induced histamine release is independent of cAMP, is unrelated to phosphodiesterase inhibition but is dependent upon inhibition of energy production.     

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.     

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.     

Antiallergic and anti-inflammatory properties of the ethanolic extract from Gleditsia sinensis

This study was carried out to determine the effects of the 70% ethanolic extract from the anomalous fruits of Gleditsia sinensis LAM. (AFGS) on experimental allergic reactions and inflammation. AFGS (200, 500, 1000 mg/kg, p.o.) dose-dependently inhibited the systemic anaphylactic shock induced by compound 48/80 in mice and cutaneous reactions induced by histamine or serotonin in rats. At doses of 500 and 1000 mg/kg, AFGS showed a clear inhibition on homologous passive cutaneous anaphylaxis in rats. In vitro, AFGS significantly reduced histamine release from rat peritoneal mast cells triggered by compound 48/80 at concentrations of 20 and 50 micro/ml. Moreover, AFGS (500, 1000 mg/kg, p.o.) showed a significant inhibition on the hind paw edema in rats and ear swelling in mice caused by carrageenin and croton oil, respectively. It also clearly inhibited the vascular permeability induced by acetic acid in mice at a dose of 1000 mg/kg. These findings demonstrate that the ethanolic extract from the anomalous fruits of Gleditsia sinensis possesses antiallergic and anti-inflammatory activities, which may be mediated by reducing the release of mediators such as histamine from mast cells and weakening the inflammatory action of these mediators.     

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.     

Effect of chloroquine on isolated mast cells.

Chloroquine liberated a relatively low amount of histamine from isolated rat mast cells. In a dose-dependent way, this drug inhibited histamine liberation from mast cells stimulated with compound 48/80, A23187, concanavalin A plus phosphatidylserine (Con A + PS) and abolished histamine liberation induced by exaprolol. The degranulation was decreased in cells stimulated with 48/80, Con A + PS and exaprolol. Chloroquine significantly inhibited the formation of thromboxane B2 in mast cells stimulated with 48/80, Con A + PS and A23187. We assume that chloroquine interferes with mast cells at a plasmic membrane site as well as intracellularly.     

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.     

The anti-allergic activity of the acetate fraction of Schinus terebinthifolius leaves in IgE induced mice paw edema and pleurisy

Schinus is a genus of the Anacardiaceae family and contains Schinus terebinthifolius, the Brazilian pepper tree that is widely used in folk medicine. We investigate the anti-allergic activity of the ethyl acetate fraction of S. terebinthifolius Raddi (ST fraction). HPLC analysis reveled that gallic acid, methyl gallate and 1,2,3,4,6-pentagalloylglucose are the major aromatic components of the fraction. Oral pre-treatment with the ST fraction (100 mg/kg) significantly inhibited paw edema induced by compound 48/80 (100 ng/paw) and to a lesser extent, the allergic paw edema (OVA, 3 mug/paw). The ST fraction (100 and 200 mg/kg) also inhibited the edema induced by histamine (100 mug/paw), preventing mast cell degranulation and, consequently, histamine release in Wistar rat peritoneal mast cells induced by C 48/80 (5 mug/mL). This histamine inhibition was also observed after mast cell pre-treatment with both methyl gallate and 1,2,3,4,6-pentagalloylglucose (100 mug/mL), the isolated compounds from the ethyl acetate fraction. Pre-treatment with the ST fraction (100 mg/kg) significantly inhibited total leukocyte and eosinophil accumulation in pleural cavities 24 h after the intrathoracic injection of OVA (12.5 mug/cavity). This effect was related to the inhibition of CCL11/eotaxin and CCL5/RANTES in pleural lavage fluid. Pre-treatment with this fraction (100 mg/kg) failed to reduce the cell influx that was observed after LPS-injection into pleural cavity (250 ng/cavity). These findings demonstrate the anti-allergic effect of the ST fraction, which includes the inhibition of edema formation and histamine release caused by mast cell degranulation and eosinophil influx into the pleural cavity probably reflected by the decreased levels of chemokines in recovered pleural lavage fluid.     

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.