Warifteine and methylwarifteine inhibited the type 2 immune response on combined allergic rhinitis and asthma syndrome (CARAS) experimental model through NF-кB pathway.

CARAS is an airway inflammation of allergic individuals, with a type 2 immune response. The pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study evaluated the alkaloids warifteine (War) and methylwarifteine (Mwar) from Cissampelos sympodialis in CARAS experimental model. Therefore, BALB/c mice were ovalbumin (OVA) sensitized and challenged and treated with both alkaloids. Treated animals showed a decrease (p < 0.05) of allergic signs as sneezing and nasal rubbings, histamine nasal hyperreactivity, and inflammatory cell migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids, main eosinophils. In the systemic context, only Mwar reduced eosinophilia, however, both alkaloids reduced the serum levels of OVA-specific IgE. Histological analysis revealed that the alkaloids decreased the inflammatory cells into the subepithelial and perivascular regions of nasal tissue and the peribronchiolar and perivascular regions of lung tissue. Hyperplasia/hypertrophy of nasal and lung goblet cells were reduced in alkaloid treated animals; however, the treatment did not change the number of mast cells. The lung hyperactivity was attenuated by reducing hyperplasia of fibroblast and collagen fiber deposition and hypertrophy of the lung smooth muscle layer. The immunomodulatory effect was by decreasing of type 2 and 3 cytokines (IL-4/IL-13/IL-5 and IL-17A) dependent by the increasing of type 1 cytokine (IFN-γ) into the BALF of treated sick animals. Indeed, both alkaloids reduced the NF-кB (p65) activation on granulocytes and lymphocytes, indicating that the alkaloids shut down the intracellular transduction signals underlie the transcription of TH2 cytokine gens.

Curine inhibits mast cell-dependent responses in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum, a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice. MATERIALS AND METHODS: To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA-12 µg/mouse) and Al(OH)3 in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1h before the challenges. RESULTS: Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D2 (PGD2) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD2 and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3. CONCLUSION: Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid curine may be beneficial for the treatment of allergic disorders.

The therapeutic properties of Carapa guianensis.

Carapa guianensis Aublet (Meliaceae), also known as andiroba, is used in popular medicine in Brazil and other countries encompassing the Amazon rainforest. Virtually all parts of the andiroba tree are utilized, including the seed's oil, which is employed to treat inflammation and infections. The medicinal properties of C. guianensis have been attributed to the presence of limonoids, which are tetranortriterpenoids. We have previously demonstrated that the oil obtained from C. guianensis seeds contains different tetranortriterpenoids, including 6α-acetoxygedunin, 7-deacetoxy-7-oxogedunin, andirobin, gedunin and methyl-angolensate. The seeds oil and this fraction of tetranortriterpenoids present marked anti-inflammatory and anti-allergic properties, by inhibiting edema formation in different experimental models in rodents, via the impairment of signaling pathways triggered by histamine, bradykinin and platelet-activating factor. Tetranortriterpenoids also impaired the production of inflammatory mediators that trigger leukocyte infiltration into the inflammatory site, including the eosinophilotactic mediators interleukin (IL)-5 and CCL11/eotaxin, as well as the inflammatory cytokines tumor necrosis factor (TNF)-α and IL-1ß. This phenomenon seems to depend on the inhibition of nuclear factor κB (NFκB) activation. We have further demonstrated that each one of the five tetranortriterpenoids listed above presented inhibitory effects on the activation of different cell populations, including mast cells, eosinophils and T lymphocytes, through which they impaired allergy and inflammation. This review will discuss the therapeutic effects of C. guianensis oil and its compounds, focusing on the scientific evidences that support its traditional use in inflammatory conditions and its anti-allergic properties.

Evaluation of dispersive liquid-liquid microextraction in the stereoselective determination of cetirizine following the fungal biotransformation of hydroxyzine and analysis by capillary electrophoresis.

We developed a capillary electrophoresis (CE) and dispersive liquid-liquid microextraction (DLLME) method to stereoselectively analyze hydroxyzine (HZ) and cetirizine (CTZ) in liquid culture media. The CE analyses were performed on an uncoated fused-silica capillary; 50mmolL(-1) sodium borate buffer (pH 9.0) containing 0.8% (w/v) S-ß-CD was used as the background electrolyte. The applied voltage and temperature were +6 kV and 15 °C, respectively, and the UV detector was set to 214 nm. Chloroform (300 µL) and ethanol (400 µL) were used as the extraction and disperser solvents, respectively, for the DLLME. Following the formation of a cloudy solution, the samples were subjected to vortex agitation at 2000 rpm for 30s and to centrifugation at 3000 rpm for 5 min. The recoveries ranged from 87.4 to 91.7%. The method was linear over a concentration range of 250-12,500 ng mL(-1) for each HZ enantiomer (r>0.998) and 125-6250 ng mL(-1) for each CTZ enantiomer (r>0.998). The limits of quantification were 125 and 250 ng mL(-1) for CTZ and HZ, respectively. Among the six fungi studied, three species were able to convert HZ to CTZ enantioselectively, particularly the fungus Cunninghamella elegans ATCC 10028B, which converted 19% of (S)-HZ to (S)-CTZ with 65% enantiomeric excess.

Anti-allergic potential of herbs and herbal natural products - activities and patents.

The increase of allergic diseases has accompanied the global population growth and the major challenge is to reduce morbidity. The currently available treatments present limitations regarding efficacy and safety. Hence, patients with chronic allergic conditions seek alternatives to achieve better control of symptoms. Many natural products have been identified as potential anti-allergic agents. In addition, plant formulations have demonstrated, in general, to be safe in clinical trials and demonstrate additional effects along with Western medicines such as synergism and modulation of the immune system. It is known that plants represent a source of new therapeutic agents and some of them have shown mechanisms of action similar to synthetic agents. However, in general, herbs and their combination are patented mainly by Asian countries to be used in food and drinks or cosmetics and dietary supplements and the anti-allergic mechanisms of action are not yet fully elucidated. In this review, we highlight relevant patent and studies with cultivated plants, plant formulations, and secondary metabolites that have been evaluated with respect to its anti-allergic potential.

Monoterpenes isolated from Minthostachys verticillata (Griseb.) Epling essential oil modulates immediate-type hypersensitivity responses in vitro and in vivo.

In a previous work, we have demonstrated that Minthostachys verticillata essential oil has immunomodulatory effects in vitro on cells from allergic patients. Here we characterized main components of M. verticillata essential oil and also tested if these compounds modulate In vitro and in vivo the immediate-type allergic reaction. Gas chromatography was used to identify main components of the essential oil. Pulegone (63.4 %), menthone (15.9 %), and limonene (2.1 %) were found as main classes. IL-13 levels were evaluated from lymphocytes cultures stimulated with allergen alone or combined with monoterpenes. All compounds stimulated cell proliferation but, interestingly, promoted a reduction of IL-13 values, limonene and the mixture of the three compounds being the most active. ß-Hexosaminidase release was determined from basophils to which essential oil or monoterpenes were added. We observed that, whichever combination of monoterpenes was used, ß-hexosaminidase release was diminished in all cases. Obtained values were even lower than those of antiallergic drug desloratadine. Essential oil and limonene inhibited mast cell activation and degranulation in the skin when testing passive cutaneous anaphylaxis, limonene being the most active. In conclusion, limonene was the compound that showed the most potent immunomodulatory activity. This fact suggests that it constitutes a promising natural alternative for a novel treatment of allergic diseases.

Anti-allergic effect of bee pollen phenolic extract and myricetin in ovalbumin-sensitized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The bee pollen is used in folk medicine to alleviate allergic reactions. The bee pollen phenolic extract (BPPE) consists in phenolic compounds (flavonoids) from plants picked by Apis mellifera bee. AIM OF THIS STUDY: Here we evaluated the anti-allergic property of the BPPE and the flavonoid myricetin (MYR) in murine model of ovalbumin (OVA)-induced allergy. MATERIALS AND METHODS: The study focused on the BPPE or myricetin treatment of OVA-sensitized BALB/c mice and their effects on the IgE and IgG1 production, pulmonary cell migration, eosinophil peroxidase (EPO) activity and anaphylactic shock reaction. RESULTS: The BPPE treatment (200mg/kg) showed inhibition of the paw edema, IgE and IgG(1) OVA-specific production, leukocyte migration to the bronchoalveolar lavage (BAL) and EPO activity in lungs. In addition, BPPE treatment showed partial protection on the anaphylactic shock reaction induced by OVA. Treatment with myricetin (5 mg/kg) also inhibited pulmonary cell migration and IgE and IgG(1) OVA-specific production. CONCLUSIONS: These results support the hypothesis the myricetin is one of the flavonoids of BPPE responsible for the anti-allergic effect and a potential tool to treat allergies.

Pharmacological study of anti-allergic activity of Syzygium cumini (L.) Skeels.

Myrtaceae is a plant family widely used in folk medicine and Syzygium and Eugenia are among the most important genera. We investigated the anti-allergic properties of an aqueous leaf extract of Syzygium cumini (L.) Skeels (SC). HPLC analysis revealed that hydrolyzable tannins and flavonoids are the major components of the extract. Oral administration of SC (25-100 mg/kg) in Swiss mice (20-25 g; N = 7/group) inhibited paw edema induced by compound 48/80 (50% inhibition, 100 mg/kg; P

Pharmacological study of anti-allergic activity of Syzygium cumini (L) Skeels

Myrtaceae is a plant family widely used in folk medicine and Syzygium and Eugenia are among the most important genera. We investigated the anti-allergic properties of an aqueous leaf extract of Syzygium cumini (L.) Skeels (SC). HPLC analysis revealed that hydrolyzable tannins and flavonoids are the major components of the extract. Oral administration of SC (25-100 mg/kg) in Swiss mice (20-25 g; N = 7/group) inhibited paw edema induced by compound 48/80 (50 percent inhibition, 100 mg/kg; P <= 0.05) and, to a lesser extent, the allergic paw edema (23 percent inhibition, 100 mg/kg; P <= 0.05). SC treatment also inhibited the edema induced by histamine (58 percent inhibition; P <= 0.05) and 5-HT (52 percent inhibition; P <= 0.05) but had no effect on platelet-aggregating factor-induced paw edema. SC prevented mast cell degranulation and the consequent histamine release in Wistar rat (180-200 g; N = 7/group) peritoneal mast cells (50 percent inhibition, 1 æg/mL; P <= 0.05) induced by compound 48/80. Pre-treatment of BALB/c mice (18-20 g; N = 7/group) with 100 mg/kg of the extract significantly inhibited eosinophil accumulation in allergic pleurisy (from 7.662 ± 1.524 to 1.89 ± 0.336 x 10(6)/cavity; P <= 0.001). This effect was related to the inhibition of IL-5 (from 70.9 ± 25.2 to 12.05 ± 7.165 pg/mL) and CCL11/eotaxin levels (from 60.4 ± 8.54 to 32.8 ± 8.4 ng/mL) in pleural lavage fluid, using ELISA. These findings demonstrate an anti-allergic effect of SC, and indicate that its anti-edematogenic effect is due to the inhibition of mast cell degranulation and of histamine and serotonin effects, whereas the inhibition of eosinophil accumulation in the allergic pleurisy model is probably due to an impairment of CCL11/eotaxin and IL-5 production.

Studies on anti-allergic constituents in the leaves and stems of Anchientia salutaris var. martiana (Violaceae).

The anti-allergic active fractionation of hexane extracts of the leaves and stems of Anchietia salutaris var. martiana (family Violaceae) was performed by monitoring their activities with an in vitro bioassay system measuring the inhibitory effects on induced histamine release from guinea pig lung cells. Three known pentacyclic triterpenes (friedelin, alpha-amyrin, beta-amyrin) were isolated, but these compounds were inactive. Aliphatic hydrocarbons and methyl esters of fatty acids (palmitic, oleic, linoleic, linolenic acids) were detected in active fractions. All compounds isolated were detected for the first time in this medicinal plant.