title: Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma.
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.
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. aceflavor@hotmail.com.
authors.forename: Daekeun
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. sinhyepark@hallym.ac.kr.
authors.forename: Sin-Hye
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. yeanjungchoi@gmail.com.
authors.forename: Yean-Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. royalskim@hallym.ac.kr.
authors.forename: Yun-Ho
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. lucia.dwiantika@gmail.com.
authors.forename: Lucia Dwi
authors.initials: LD
authors.lastname: Antika
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. nurinahabibah@gmail.com.
authors.forename: Nurina Umy
authors.initials: NU
authors.lastname: Habibah
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. mitholy@hallym.ac.kr.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Kang
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea. yhkang@hallym.ac.kr.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D000818:Animals; D001249:Asthma / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D002417:Cattle; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D004032:Diet; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006596:Hexosaminidases / Q000378:metabolism; D006967:Hypersensitivity / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D054467:Phospholipases A2; D011453:Prostaglandins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D012710:Serum Albumin, Bovine; D000072377:Syk Kinase; D013997:Time Factors
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D044949:Kaempferols; D011453:Prostaglandins; D012710:Serum Albumin, Bovine; C006552:kaempferol; D051546:Cyclooxygenase 2; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C000606898:Syk protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D054467:Phospholipases A2; D006596:Hexosaminidases
keywords: airway thickening; asthma; bronchoconstriction; cyclooxygenase 2; kaempferol