Abstract
Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10–20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy.
Highlights
Allergic responses, including itching, runny nose, coughing, and trouble breathing, commonly occur following the invasion of allergens [1,2,3]
Among the various allergic diseases, bronchial asthma causes an anaphylactic response triggered by the cross-linking of high-affinity Fc receptors for immunoglobulin E (IgE) located on the surface of mast cells and basophils [4,5]
Prostaglandin D2 (PGD2) is a major PG produced by mast cells, recruits Th2 cells, eosinophils, and basophils and is critical to the development of allergic diseases [12]
Summary
Allergic responses, including itching, runny nose, coughing, and trouble breathing, commonly occur following the invasion of allergens [1,2,3]. Among the various allergic diseases, bronchial asthma causes an anaphylactic response triggered by the cross-linking of high-affinity Fc receptors for immunoglobulin E (IgE) located on the surface of mast cells and basophils [4,5]. It is found that upon the stimulation of both mast cells and basophils through the activation of IgE receptors chemicals, such as histamine and serotonin, are released to evoke acute airway inflammation [6,7]. Mast cells are crucial effector cells in allergic disorders, releasing lipid mediators and eicosanoids, including prostaglandins (PGs) and leukotrienes, that cause airway constriction via smooth muscle contraction [10,11]. Prostaglandin F2α (PGF2α) exerts the potent secretagogue activity of the mucus secretion in bronchi and trachea, stimulates the contraction of uterine and bronchial smooth muscle, and participates in the inflammation modulation and blood vessel vasoconstriction [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
