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Inula japonica extract inhibits mast cell-mediated allergic reaction and mast cell activation
Authors:Yue Lu  Ying Li  Meihua Jin  Ju Hye Yang  Xian Li  Guang Hsuan Chao  Hyo-Hyun Park  Young Na Park  Jong Keun Son  Eunkyung Lee  Hyeun Wook Chang
Affiliation:1. College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea;2. School of Pharmaceutical Sciences, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;3. Research and Development Division, Korea Promotion Institute for Traditional Medicine Industry, Gyeongsan 712-260, Republic of Korea
Abstract:

Ethnopharmacological relevance

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.

Materials and 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, Ca2+ influx, and immunoblotting of various signaling molecules.

Results

IFE inhibited degranulation and the generation of eicosanoids (PGD2 and LTC4) 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 Ca2+ and phosphorylation of the mitogen-activated protein kinases (MAPKs), PLCγ1, and cPLA2 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.
Keywords:IFE, Inulae Flos extract   BMMCs, bone marrow-derived mast cells   IL-3, interleukin-3   LTC4, leukotriene C4   SCF, stem cell factor   cPLA2, cytosolic phospholipase A2   MAPKs, mitogen-activated protein kinases   PLCγ, phospholipase Cγ   AA, arachidonic acid   ERK1/2, extracellular signal-regulated kinase 1/2   JNK, c-jun N-terminal kinases
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