Deaths due to asthma are often preventable, but they continue to occur as the result of poor symptom management 4, 5. The exact incidence rate of asthma occurrence is difficult to determine due to the lack of conclusive data 4. This airway restriction and constricted air passage leads to the characteristic symptoms of asthma, including coughing, wheezing, chest tightness, and shortness of breath.Ĭurrently, the principal limitation in asthma treatment is the absence of a safe, permanent cure. The excess mucus is deposited along the walls of the airways, leading to their constriction and subsequent restriction in the passage of air 2, 3. The airways become swollen, and the epithelial cells lining the airways are stimulated to over-produce mucus. Upon subsequent challenges with an allergen, the humoral response activates further T H 2- and IgE‑mediated inflammation of the airways 3. The T H 2 response subsequently activates the humoral response and the production of antibodies. When a susceptible individual is exposed to allergens, antigen-presenting cells (APCs) of the airways in the lungs are activated, leading to the release of pro-inflammatory cytokines, including TNFα, NFκB, chemokines, and other mediators that activate the T H 2 immune response 2, 3. Clinical manifestations of the disease are characterized by an infiltration of the airways with eosinophils, mast cells, and CD4 + T H 2 cells 2. Asthma affects 334 million individuals worldwide, with up to 300,000 deaths and 22 million disability-adjusted life years lost annually 1. Most over-the-counter or prescription medications, however, may result in refractory disease within a short timespan and/or are ineffective in a substantial percentage of patients. We also found that fisetin potentially acts by blocking the TH2 response, including pro-inflammatory signaling molecules such as NFκB, STAT6, HIF1α, iNOS, TNFα and IL13.Ĭonclusion: Our study showed that a low dose of fisetin (50 nM), administered orally in an aqueous solution, may offer a safe and economical therapeutic strategy for asthma.Īsthma is a debilitating disease, particularly if not managed in the early stages. Acute inflammation associated with asthma was also reduced, as determined by inhibition of cellular infiltration, serum IgE, and serum nitric oxide (NO), as well as a reduction in goblet cell hyperplasia. Results: In mice treated with fisetin, AHR was significantly reduced, as shown by plethysmography. The mice were sacrificed, and their tissues removed to evaluate a range of disease parameters. The mice were subsequently evaluated with whole-body plethysmography, 24 hours after the last intratracheal challenge, to measure airway hyper-responsiveness (AHR). Methods: We induced asthma in BALB/c mice using intraperitoneal sensitization and repeated intratracheal challenges with ovalbumin (Ova), followed by oral administration of 0.6 mg/kg (MPK) aqueous fisetin (primary stock in DMSO) before each intratracheal challenge. In this study, we investigated the use of fisetin, a readily available natural product found in fruits, such as strawberries and apples, to treat acute asthma in a preclinical mouse model. Drugs, such as corticosteroids, β2-agonists, and anticholinergics, only temporarily reduce symptoms and have various adverse effects. Currently, no permanent therapeutic strategies are available for the treatment of asthma. Background: Asthma is a very common, non-communicable, chronic respiratory disease, with a high incidence rate worldwide.
0 kommentar(er)
