Effects Of Mast Cell Stabilization Research Articles

In Vivo Pharmacological Testing of Herbal Drugs for Anti-Allergic and Anti-Asthmatic Properties.

Background:Asthma is a chronic inflammatory disease characterized by reversible airway obstruction, hyperresponsiveness, and remodeling. Asthma prevalence has increased significantly globally over the last decade, and it remains incurable to this date.Aims and Objectives:The present study evaluated some of the antiasthmatic medicinal plants to assess their mode of action.Materials and Method:Animal models for milk-induced leukocytosis, milk-induced eosinophilia, mast cell degranulation, clonidine-induced catalepsy, and active paw anaphylaxis were used to assess the pharmacological effects of Ammi visnaga, Medicago sativa, and Urtica dioica.Results:Mice pretreated with diazepam, methanolic extract of M. sativa, and U. dioica exhibited significant (P < 0.05) inhibition in milk-induced leukocytosis. However, only M. sativa showed statistically significant (P < 0.05) results. All plants showed a statistically significant (P < 0.05) tendency to decrease milk-induced eosinophilia. Methanolic extracts of all plants significantly (P < 0.05) protected mast cells against degranulation by clonidine. A. visnaga and U. dioica significantly (P < 0.05) protected mice against clonidine-induced catalepsy. An acute treatment by M. sativa potentiated the catalepsy, while it significantly inhibited the catalepsy (P < 0.05) upon chronic treatment. In the allergic inflammation model, methanolic extracts of all plants under study decreased paw thickness in a statistically significant manner (P < 0.05).Conclusion:All the three plants in this study demonstrated anti-inflammatory and antihistaminic effects, as well as decreased paw thickness, validate anti-allergic properties. A. visnaga showed a mast cell-stabilizing effect. A. visnaga and U. dioica inhibited the histamine-mediated clonidine-induced catalepsy from mast cells which proves the antihistaminic activity of these plants.

Bronchodilator and Mast Cell Stabilizer Effect of Siddha Formulation Seenthil Chooranam

The present study aimed to evaluate anti-asthmatic activity of a classical Siddha formulation Seenthil chooranam (SC) by mast cell stabilizing effect and broncho dilator property by in-vivo method. Preliminary phytochemical and HPTLC analysis of SC were determined as per standard protocols. Phytochemical analysis of aqueous extract gave positive test for carbohydrates, phenols, glycosides, saponins, flavonoids, tannins and terpenoids. HPTLC finger print analysis of the aqueous extract showed the presence of possible number of components. The results of the in-vivo study demonstrate that SC has potent broncho dilator property with significant (***p<0.001) mast cell stabilizing activity and decrease in leukocytosis in dose dependent manner. These findings are clearly indicative of the role of SC as potent inhibitor of mast cell degranulation and ability to control the leukocytosis, have bronchodilation and hence can be used for the management of asthma supporting the traditional claims

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

Background: Macrolides, such as clarithromycin, have antiallergic properties. Since exocytosis in mast cells is detected electrophysiologically via changes in membrane capacitance (Cm), the absence of such changes due to the drug indicates its mast cell-stabilizing effect. Methods: Employing the whole-cell patch clamp technique in rat peritoneal mast cells, we examined the effects of clarithromycin on Cm during exocytosis. Using a water-soluble fluorescent dye, we also examined its effect on deformation of the plasma membrane. Results: Clarithromycin (10 and 100 μ<smlcap>M</smlcap>) significantly inhibited degranulation from mast cells and almost totally suppressed the GTP-γ-S-induced increase in Cm. It washed out the trapping of the dye on the surface of mast cells. Conclusions: This study provides for the first time electrophysiological evidence that clarithromycin dose-dependently inhibits the process of exocytosis. The mast cell-stabilizing action of clarithromycin may be attributable to its counteractive effect on plasma membrane deformation induced by exocytosis.

Anti-allergic actions of rottlerin from Mallotus philippinensis in experimental mast cell-mediated anaphylactic models

Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of the allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Rottlerin is an active molecule isolated from Mallotus philippinensis, a medicinal plant used in Ayurvedic Medicine System for anti-allergic and anti-helminthic treatments. The present study investigated potential anti-allergic effects of rottlerin in animal models of IgE-dependent anaphylaxis and the anti-allergic mechanisms of action of rottlerin in mast cells. Anti-allergic actions of rottlerin were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in anaphylactic contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of rottlerin was examined in RBL-2H3 mast cell line. Anti-allergic signaling mechanisms of action of rottlerin in mast cells were also examined. Rottlerin prevented IgE-mediated cutaneous vascular extravasation, hypothermia, elevation in plasma histamine level and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, rottlerin suppressed ovalbumin-induced guinea pig bronchial smooth muscle contraction. Furthermore, rottlerin concentration-dependently blocked IgE-mediated immediate release of β-hexosaminidase from RBL-2H3 mast cells. Rottlerin was found to inhibit IgE-induced PLCγ1 and Akt phosphorylation, production of IP3 and rise in cytosolic Ca2+ level in mast cells. We report here for the first time that rottlerin possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing rottlerin for the treatment of allergic asthma and other mast cell-mediated allergic disorders.

Anti‐allergic action of anti‐malarial drug artesunate in experimental mast cell‐mediated anaphylactic models

Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi-synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti-malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti-allergic effects of artesunate in animal models of IgE-dependent anaphylaxis. Anti-allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin-induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of artesunate was examined in RBL-2H3 mast cell line and in mature human cultured mast cells. Anti-allergic signaling mechanisms of action of artesunate in mast cells were also investigated. Artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, artesunate suppressed ovalbumin-mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration-dependently blocked IgE-mediated degranulation of RBL-2H3 mast cells and human culture mast cells. Artesunate was found to inhibit IgE-induced Syk and PLCγ1 phosphorylation, production of IP(3) , and rise in cytosolic Ca(+2) level in mast cells. We report here for the first time that artesunate possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders.

Cardioprotective effects of mast cell modulators in ischaemia-reperfusion- induced injury in rats

This study was designed to investigate the cardioprotective effects of pharmacological interventions, modulating resident cardiac mast cells, on ischemia-reperfusion-induced injury. Isolated rat hearts were mounted on Langendorff apparatus and subjected to 30-min global ischemia followed by 120-min reperfusion. The extent of mast cell degranulation was assessed by release of mast cell peroxidase (MPO). The release of lactate dehydrogenase (LDH) and creatine kinase (CK) and estimation of infarct size were used to assess the extent of myocardial injury. Left ventricle developed pressure (LVDP) and its derivatives, that is, dp/dt(max) and dp/dt(min), were recorded to evaluate the postischemic recovery of the contractility of heart. Ketotifen (0.1 microM) and low-dose carvedilol (0.1 microM), without beta-blockade activity, attenuated ischemia-reperfusion-induced mast cell degranulation along with the reduction in myocardial injury, suggesting the protective effects of mast cell stabilization during ischemia and reperfusion. Administration of compound 48/80 (1 microg/ml), a specific mast cell degranulating agent, completely degranulated cardiac mast cells before global ischemia. Moreover, it also resulted in the attenuation of ischemia-reperfusion-induced myocardial injury. Decreased release of cytotoxic mediators from already degranulated (empty) mast cells during sustained global ischemia may be responsible for the cardioprotective effects of compound 48/80. Administration of carvedilol or ketotifen after compound 48/80 perfusion did not further enhance the cardioprotective effects, suggesting that the cardiac mast cells may be the common target site for ketotifen, compound 48/80 and low-dose carvedilol.

Development and Sequels of Intestinal Inflammation in Nematode-Infected Rats: Role of Mast Cells and Capsaicin-Sensitive Afferents

Objectives: To determine whether intestinal mast cells and capsaicin-sensitive afferent nerves are involved in the development and sequels of Nippostrongylus brasiliensis-induced intestinal inflammation in rats. Methods: Two series of experiments were performed. In the first series, six groups of 8 rats were used to study the effects of mast cell stabilization by ketotifen. In the second series, six groups of 6 rats were used to study the effects of gut extrinsic sensory neuron depletion by capsaicin. For each series, four groups of rats were infected with N. brasiliensis and two groups were not infected. Results: Infection with N. brasiliensis resulted in an increase of myeloperoxidase (MPO) activity and mast cell numbers at day 12 postinfection; MPO returned to preinfection levels by day 35 while mast cell numbers remained elevated at that time. In ketotifen-treated infected rats, the increase of MPO at day 12 was less pronounced, but MPO activity remained elevated and mast cell numbers were increased at day 35. In capsaicin-treated infected rats, the MPO increase at day 12 was augmented, and MPO was still not returned to preinfection values by day 35; in contrast, the increase of mast cell numbers at days 12 and 35 was not modified by afferent nerve depletion. Conclusion: Mast cell stabilization decreased jejunal inflammation during the acute stage (day 12), but prolonged the inflammatory process until at least day 35 postinfection. The data also confirmed the protective role of gut extrinsic sensory neurons against intestinal inflammation in a model of nematode infection and revealed that these afferent nerves do not seem crucial for the development of nematode-induced hypermastocytosis.

Effects of Mast-Cell Stabilization in Cerulein-Induced Acute Pancreatitis in Rats

Acute pancreatitis is characterized by inflammationof the pancreas that ranges from mild inflammationto severe necrotizing pancreatitis (1-3).Several factors can initiate a cascade of pathologic events that results in AP (4). A key feature in thispathogenesis is inflammatory reaction. However,causes of exaggerated inflammatory reaction are notwell understood (4,5). Since the pathogenesis of pancreatitisis still unclear, most of the treatment modalitiesare largely supportive and independent of thepathogenesis (1,2).

Role of mucosal mast cells in early vascular permeability changes of intestinal DTH reaction in the rat.

Previously, it was shown that depletion and stabilization of the mucosal mast cell around the time of challenge were very effective in reducing delayed-type hypersensitivity (DTH) reactions in the small intestine of the rat. The role of mucosal mast cells in the early component of intestinal DTH reaction was further investigated in this study. In vivo small intestinal vascular leakage and serum levels of rat mast cell protease II (RMCP II) were determined within 1 h after intragastric challenge of rats that had been sensitized with dinitrobenzene 5 days before. A separate group of rats was used to study vasopermeability in isolated vascularly perfused small intestine after in vitro challenge. To investigate the effects of mast cell stabilization on the early events of the DTH reaction, doxantrazole was used. The influence of sensory nerves was studied by means of neonatal capsaicin-induced depletion of sensory neuropetides. Within 1 h after challenge, a significant increase in vascular permeability was found in vivo as well as in vitro. This was associated with a DTH-specific increase in RMCP II in the serum, indicating mucosal mast cell activation. In addition, doxantrazole treatment and caspaicin pretreatment resulted in a significant inhibition of the DTH-induced vascular leakage and an increase in serum RMCP II. These findings are consistent with an important role for mucosal mast cells in early vascular leakage changes of intestinal DTH reactions. In addition, sensory nervous control of mucosal mast cell activation early after challenge is demonstrated.