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Allergic asthma is associated with airway epithelial cell mucous metaplasia and mucin hypersecretion, but the consequences of mucin hypersecretion on airway function are unclear. Recently, a peptide derived from the myristoylated alanine-rich C kinase substrate protein NH(2)-terminal sequence (MANS) was shown to inhibit methacholine (MCh)-induced mucin secretion from airway mucous cells by >90%. We studied the effect of intranasal pretreatment with this peptide on specific airway conductance (sGaw) during challenge with MCh in mice with allergen-induced mucous cell metaplasia. sGaw was noninvasively measured in spontaneously breathing restrained mice, using a double-chamber plethysmograph. Pretreatment with MANS peptide, but not a control peptide [random NH(2)-terminal sequence (RNS)], resulted in partial inhibition of the fall in sGaw induced by 60 mM MCh (mean +/- SE; baseline 1.15 +/- 0.06; MANS/MCh 0.82 +/- 0.05; RNS/MCh 0.55 +/- 0.05 cmH(2)O/s). The protective effect of MANS was also seen in mice challenged with allergen for 3 consecutive days to increase airway hyperresponsiveness, although the degree of protection was less (baseline 1.1 +/- 0.08; MANS/MCh, 0.65 +/- 0.06; RNS/MCh 0.47 +/- 0.03 cmH(2)O/s). Because routine sGaw measurement in mice includes nasal airways, the effectiveness of MANS was also confirmed in mice breathing through their mouths after nasal occlusion (baseline 0.92 +/- 0.05; MANS/MCh 0.83 +/- 0.06; RNS/MCh 0.61 +/- 0.03 cmH(2)O/s). In all instances, sGaw in the MANS-pretreated group was approximately 35% higher than in RNS-treated controls, and mucous obstruction accounted for approximately 50% of the MCh-induced fall in sGaw. In summary, mucin secretion has a significant role in airway obstruction in a mouse model of allergic asthma, and strategies to inhibit mucin secretion merit further investigation.

Curcumin (diferuloylmethane), a natural product from the rhizomes of Curcuma longa is a yellow colored polyphenolic phytochemical which has been in use for a long time for the treatment of swelling, twisting and wounds. The Indian system of medicine uses curcumin, present in its raw form in the plant extract, as a wound healer and inhibitor of swelling. As a pure compound also, it has been found to possess antitumor, anti-cancer and anti-inflammatory activities. Several studies have clearly indicated that curcumin possesses a variety of pharmacological effects such as in wound-healing, 1) anti-oxidant 2-4) and anti-inflammatory activities. 5) Certain recent studies indicated that curcumin may exert its anti-inflammatory properties by: a) suppressing the activation of NF-kappaB through inhibition of IKK activity, 6) b) significantly inhibiting the LPS induced proinflammatory cytokines IL-1beta and IL-8 7) and c) inhibiting iNOS production and by scavenging NO radicals. 8) There is some evidence that curcumin has anti-spasmodic effect on smooth muscle of dogs' intestine in-vivo and vas-defrens of guinea pig in-vitro. 9)Based on these inflammatory and anti-spasmodic properties of curcumin, we hypothesized that it could have anti-asthmatic activity as well because asthma is a chronic airway inflammatory disorder.Asthma pathogenesis involves airway inflammation coupled with airway hyperresponsiveness (AHR) to a variety of physical and pharmacological stimuli. The incidence of asthma is on the rise globally and is reaching epidemic proportions.10) The already existing remedies for asthma are known to possess detrimental side effects on prolonged use. Therefore, there is a need to explore for new anti-asthmatic agents, preferably a plant-based drug that has negligible side effects.For our study, we selected a guinea pig model because of its marked airway reactivity and a good similarity to the airways of asthmatic human subjects. 11) To test the effect of curcumin, we sensitized the animals with ovalbumin (OVA) to develop the characteristic features of asthma: antigen induced airway constriction and airway hyperreactivity to histamine. We report here for the first time that curcumin inhibits allergen induced airway constriction and airway hyperreactivity to histamine in guinea pigs. MATERIALS AND METHODSAnimals Male guinea pigs of Dunkin-Hartley strain (National Institute of Nutrition, Hyderabad, India), 8-10 weeks old, weighing 300-350 g were used and acclimatized at least one week under laboratory conditions before conducting the experiment. Animals were allowed free access to food and water throughout the experiment. Experimental protocols were approved by the institutional ethical committee. Six groups of animals (nϭ6) were used for the study.Sensitization Animals were sensitized with 3 intra-peritoneal (i.p.) injections of 20 mg OVA (Sigma Chemical, Grade V, St. Louis, MO, U.S.A.) adsorbed on 10 mg alum, Al 2 (OH) 3 in 0.5 ml 0.9% saline on alternate days. After 3 weeks of last i.p. injection, the animals were che...

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Our study showed that luteolin treatment during and after sensitization significantly attenuated the asthmatic features in experimental mice. Therefore, luteolin could be used either as a lead molecule to identify an effective antiasthma therapy or as a means to identify novel anti-asthma targets.

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Background: Asthma is a chronic respiratory disease, which needs a safer medication preferably in inhalation form. In view of this, we have evaluated the effect of inhaled carbenoxolone (CBX), a herbal-derived compound, on asthma in a mouse model. Methods: Mice were sensitized and challenged with ovalbumin (OVA) to develop certain characteristic features of asthma such as airway hyperreactivity (AHR), airway eosinophilia, lung inflammation and mucus hypersecretion. To evaluate the effect of CBX on the above asthmatic features, CBX (2.5, 5 and 10 mg/ml, 3 ml) or vehicle (water) was given by inhalation. AHR was determined using whole-body plethysmography. Infiltration of eosinophils was estimated by microscopy. Lung inflammation and mucus hypersecretion were assessed using hematoxylin and eosin, and periodic acid-Schiff staining, respectively. Th-2 cytokines, IL-4 and IL-5 were measured in bronchoalveolar lavage (BAL) fluid and IgE in sera. To identify the possible mode of CBX action, we measured corticosterone levels in the BAL fluid and 5-lipoxygenase (5-LO) expression in the lungs. Results: CBX (5 mg/ml) inhalation markedly alleviated AHR (p = 0.0032) and reduced lung inflammation and mucus hypersecretion. Also, it prevented the increase in IL-4 (p = 0.0192), IL-5 (p = 0.0116) and eosinophils (p < 0.0005) in the BAL fluid, and OVA-specific IgE levels (p = 0.00061) in sera. 5-LO expression was also markedly reduced. However, corticosterone levels were not affected. Conclusions: Inhaled CBX alleviates the asthmatic features in mice and could be a potent nebulized therapy in clinical asthma.