Date Published: February 3, 2019
Author(s): Douglas B. Aidoo, David D. Obiri, Newman Osafo, Aaron O. Antwi, Leslie B. Essel, Babatunde M. Duduyemi, Martins Ekor.
Bergapten (5-methoxypsoralen, 5-MOP) is a plant-derived furocoumarin with demonstrated anti-inflammatory action. The present study investigated its effects on allergic inflammation in two related pathways of mast cell degranulation. Compound 48/80 and lipopolysaccharide (LPS) were used to activate the IgE-independent pathway while bovine serum albumin (BSA) was used as allergen for the IgE-dependent pathway. The modulatory effect of bergapten on mast cell degranulation, neutrophil extravasation, protein concentration, lung histopathology, and oxidative stress was assessed. Bergapten at 10, 30, and 100 μg/ml for 15 min stabilized mast cells in rat mesenteric tissue from disruption in vitro and when administered in vivo at 3, 10, and 30 mg kg−1 for 1 h protected mice from fatal anaphylaxis induced by compound 48/80. Similarly, treatment of LPS-challenged mice with bergapten (3, 10, and 30 mg kg−1) for 24 h significantly decreased neutrophil infiltration into bronchoalveolar lavage fluid, mean protein concentration, and inflammatory cell infiltration of pulmonary tissues when compared to the saline-treated LPS-challenged control. In addition, lung histology of the bergapten-treated LPS-challenged mice showed significantly less oedema, congestion, and alveolar septa thickening when compared to the saline-treated LPS-challenged disease control. LPS-induced oxidative stress was significantly reduced through increased tissue activities of catalase and superoxide dismutase and reduced malondialdehyde levels on treatment with bergapten. In the triple antigen-induced active anaphylaxis, daily administration of bergapten at 3, 10, and 30 mg kg−1 for 10 days, respectively, protected previously sensitized and challenged mice against anaphylactic shock. Overall, our study demonstrates the ability of bergapten to attenuate allergic airway-induced hypersensitivity in murine models of inflammation, suggesting its possible therapeutic benefit in this condition.
Allergy is one of the common diseases which affect mankind, and it is also responsible for significant morbidity and mortality. The prevalence of allergic diseases such as anaphylaxis, asthma, rhinitis, and atopic dermatitis has increased in recent times despite the general health improvement in the population [1, 2].
We explored the effects of bergapten (5-MOP) on allergic inflammation in two related pathways of mast cell degranulation: an IgE-independent pathway in which, respectively, compound 48/80 and lipopolysaccharide (LPS) were used to induce inflammation and an IgE-dependent pathway in which bovine serum albumin (BSA) was used as a source of allergen. The former is mediated by interaction of IgG with macrophages and basophils as the major pathways while the latter is elicited by aggregation of IgE bound to high affinity receptors (FcεRI) on surface of mast cells and basophils .
Taken together, the present study reveals the potential benefit of bergapten in managing allergy-related inflammatory conditions as demonstrated by its ability to attenuate allergic airway-induced hypersensitivity in murine models of inflammation.