Inula japonica extract inhibits mast cell-mediated allergic reaction and mast cell activation.
BACKGROUND
The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of bronchitis, digestive disorders, and inflammation. However, the mechanisms underlying its anti-inflammatory effects remain yet to be elucidated. The objectives of this study were 1) to assess the anti-allergic activity of the ethanol extract of flowers of Inula japonica extract (IFE) in vivo, 2) to investigate the mechanism of its action on mast cells in vitro, and 3) to identify its major phytochemical compositions.


METHODS
The anti-allergic activity of IFE was evaluated using mouse bone marrow-derived mast cells (BMMCs) in vitro and a passive cutaneous anaphylaxis (PCA) animal model in vivo. The effects of IFE on mast cell activation were evaluated in terms of degranulation, eicosanoid generation, Ca(2+) influx, and immunoblotting of various signaling molecules.


RESULTS
IFE inhibited degranulation and the generation of eicosanoids (PGD(2) and LTC(4)) in stem cell factor (SCF)-stimulated BMMCs. Biochemical analysis of the SCF-mediated signaling pathways demonstrated that IFE inhibited the activation of multiple downstream signaling processes including mobilization of intracellular Ca(2+) and phosphorylation of the mitogen-activated protein kinases (MAPKs), PLCγ1, and cPLA(2) pathways. When administered orally, IFE attenuated the mast cell-mediated PCA reaction in IgE-sensitized mice. Its major phytochemical composition included three sesquiterpenes, 1-O-acetylbritannilactone, britanin and tomentosin.


CONCLUSIONS
This study suggests that IFE modulates eicosanoids generation and degranulation through the suppression of SCF-mediated signaling pathways that would be beneficial for the prevention of allergic inflammatory diseases. Anti-allergic activity of IFE may be in part attributed particularly to the presence of britanin and tomentosin as major components evidenced by a HPLC analysis.
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Yue
Y
Lu
Ying
Y
Li
Meihua
M
Jin
Ju Hye
JH
Yang
Xian
X
Li
Guang Hsuan
GH
Chao
Hyo-Hyun
HH
Park
Young Na
YN
Park
Jong Keun
JK
Son
Eunkyung
E
Lee
Hyeun Wook
HW
Chang
D000707:Anaphylaxis / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism; D035264:Flowers; D038143:Inula / Q000737:chemistry*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism
D018926:Anti-Allergic Agents; D015777:Eicosanoids; D010936:Plant Extracts; D019089:Stem Cell Factor; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium