Asthma is chronic and multi-factorial inflammatory disease hence single allergen induced asthma in an animal is not identical to clinical asthma. Therefore, we developed a novel experimental model of asthma in rats using ovalbumin (OVA) and lipopolysaccharide (LPS) allergens. Rats were divided into four groups; normal (NC), OVA, LPS, and OVA-LPS treated. Rats were sensitized with OVA (100 μg/kg, adsorbed in 100 mg/mL aluminum hydroxide, i.p.), LPS (10 μg/kg, i.p.) and both (OVA-LPS) on 7th, 14th, 21st days and was followed by challenge with OVA (1%w/v), LPS (1%w/v), OVA (0.5%w/v) and LPS (0.5%w/v) for 30 min thrice/week for three weeks in the OVA, LPS and OVA-LPS groups, respectively. On 41 day, lung function parameters (respiration rate, tidal volume, and airflow rate), total and differential leukocytes count in the blood as well as BALf and inflammatory cytokines (IL-4, IL-5, and IL-13) in serum were measured. Histology of lungs was performed.The results suggested that the tidal volume and airflow rate were significantly decreased while respiration rate, total and differential leukocytes count in blood as well as BALf and serum cytokines level were significantly increased in the OVA-LPS as compared to NC, OVA, and LPS.In conclusion, the combination of OVA and LPS induced phenotypes of severe asthma with eosinophilic, neutrophilic and lymphocytic inflammation.
The aim of this study was to prepare and characterise oral delivery of morin hydrate-loaded micellar nanocarriers using Pluronic P127 and Pluronic F123 for the effective management of Alzheimer's disease. After administration of formulation brain and blood drug concentration were found to be highest for optimised morin hydrate-loaded micellar nanocarriers as compared to plain morin hydrate. Significant (p < 0.05) reduction in assessed pharmacodynamic parameters was observed after administration of morin hydrate-loaded micellar nanocarriers as compared to disease control group. Chronic treatment with morin-loaded micelles significantly increased the memory in AlCl induced Alzheimer's disease in Wistar rats.
Toll-like receptor-4 (TLR4) is a key component of the innate immune system and activation of TLR4 signaling has a significant role in the pathogenesis of asthma. Therefore, our objective was to identify the natural TLR4 antagonist and evaluate its activity in experimentally induced asthma. Soya lecithin origin phosphatidylcholine (soya PC) was identified as a natural TLR4 antagonist by computational study. Based on the computational study, TLR4 antagonist activity of soya PC was confirmed in in vitro lipopolysaccharide (LPS)-induced neutrophil adhesion assay. In the in vivo study, rats were sensitized with ovalbumin (OVA) (100 μg/kg, i.p.) on the 7th, 14th and 21st days and challenged intranasally with OVA (100 μg/100 μL) and LPS (10 ng/100 μL), 4 days/wk for 3 weeks. At the end of the experiment, we performed lung function parameters (respiratory rate, tidal volume, airflow rate), inflammatory cytokines (interleukin [IL]-4, IL-5, IL-13), total and differential leukocytes in blood as well as bronchoalveolar lavage fluid (BALf) and histological examinations. The computational study indicated that TLR4 antagonist activity of soya PC is due to linoleic acid (18:2) fatty acid chain. Soya PC significantly suppressed the LPS-induced neutrophil adhesion in a concentration-dependent manner to 1 μg/mL. The treatment of soya PC (5 and 10 mg/kg, 18 days, i.p.) significantly improved the lung function parameters, total and differential leukocyte counts in blood and BALf in asthmatic rats. This efficacy of soya PC was in extent similar to dexamethasone (2.5 mg/kg, 18 days, i.p.). However, soya PC was superior to dexamethasone in terms of benefits. The protective action of soya PC may be due to TLR4 antagonist activity and linoleic acid composition.
Ulcerative colitis (UC) is an inflammatory chronic disease primarily affecting the colonic mucosa; the extent and severity of colon involvement are variable. Ulcerative colitis is identified by mucus diarrhea, tenesmus, bowel distension, and anemia. 5-aminosalicylic acid drugs, steroids, and immune suppressants are used for the therapy of ulcerative colitis. The mainchallenges in the management of thediseaseare drug-related side-effects and local targeting. To overcome these challengesprobiotics and micro and Nanoparticulate systemauspiciousapproaches to overcome drug-related adverse side effects and local targeting.Upon ingestion, the probiotics can result in beneficial health effects. Probiotics and micro and nanoparticulate approaches for suitable targeting and overcome the drug-associated side effect. Probiotics are mainly used as gut modulators but are also nowadays explored for their use in ulcerative colitis.The current therapeutic goals are to achieve clinical remission along with mucosal healing, avoidance of complications such as side effects of the drug and to improve the quality of life. The use of probiotics to increase the health of the intestine and used to block or manage intestinal disorders. They may prevent the induction of inflammatory reactions. Probiotics must be inspected for efficacy in the prevention and management of a wide spectrum of gastrointestinal diseases, like antibiotic-associated diarrhea.Micro and Nanoparticulate drug delivery system has been achieving huge importance for targeting of the drug to colon locally at a controlled and sustained rate.
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