PMID- 26707911 OWN - NLM STAT- MEDLINE DCOM- 20161027 LR - 20170103 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 37 IP - 2 DP - 2016 Feb TI - Inhibitory effect of fermented Arctium lappa fruit extract on the IgE-mediated allergic response in RBL‑2H3 cells. PG - 501-8 LID - 10.3892/ijmm.2015.2447 [doi] AB - Arctium lappa fruit has been used in traditional medicine, and it is known to exert beneficial effects, such as antioxidant, anti-inflammatory and anticancer effects. However, the effects of the Arctium lappa fruit on the allergic response remain unknown. In this study, we evaluated the anti-allergic effects of Arctium lappa fruit extract (AFE) and its fermented form (F-AFE) using immunoglobulin E (IgE)-activated RBL‑2H3 cells. To investigate the anti-allergic effects of AFE or F-AFE, we examined the release of beta-hexosaminidase, a key biomarker of degranulation during an allergic reaction, and the production of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) in the cells treated with or without the above-mentioned extracts. AFE weakly inhibited the release of beta-hexosaminidase, whereas F-AFE significantly suppressed the release of beta-hexosaminidase in a dose-dependent manner. Consistently, F-AFE suppressed the production of TNF-alpha and PGE2 in a dose-dependent manner. F-AFE exerted an inhibitory effect on the production of beta-hexosaminidase, TNF-alpha and PGE2 with an IC50 value of 30.73, 46.96 and 36.27 microg/ml, respectively. Furthermore, F-AFE inhibited the phosphorylation of Lyn, Fyn and Syk, which are involved in the FcepsilonRI signaling pathway, that of phosphoinositide phospholipase C (PLC)gamma1/2 and protein kinase C (PKC)delta, which are associated with the degranulation process, as well as that of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK), p38 and Akt, which are associated with cytokine expression. In the late phase, F-AFE partially suppressed the phosphorylation of cytosolic phospholipase A2 (cPLA2), but not the expression of cyclooxygenase (COX)-2. To compare and identify the major components of the two extracts, we used high-performance liquid chromatography. The levels of arctigenin, one of the major compounds, were elevated 6-fold in F-AFE compared with AFE, whereas the levels of arctiin, an arctigenin glycoside, were decreased in F-AFE by approximately 57.40%. These results suggest that arctigenin plays an important role in the anti-allergic effects of F-AFE. Taken together, F-AFE containing anti-allergic phytochemicals, including arctigenin, inhibited the activation of the FcepsilonRI receptor induced by the antigen‑IgE complex. Such effects may provide further information for the development of a phytomedicine for allergic diseases. FAU - Yoo, Jae-Myung AU - Yoo JM AD - Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea. FAU - Yang, Ju Hye AU - Yang JH AD - Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea. FAU - Yang, Hye Jin AU - Yang HJ AD - Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea. FAU - Cho, Won-Kyung AU - Cho WK AD - Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea. FAU - Ma, Jin Yeul AU - Ma JY AD - Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151228 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Plant Extracts) RN - 0 (Receptors, IgE) RN - 0 (Tumor Necrosis Factor-alpha) RN - 37341-29-0 (Immunoglobulin E) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Fyn protein, mouse) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn) RN - EC 2.7.10.2 (SYK protein, human) RN - EC 2.7.10.2 (Syk Kinase) RN - EC 2.7.10.2 (Syk protein, mouse) RN - EC 2.7.10.2 (lyn protein-tyrosine kinase) RN - EC 2.7.10.2 (src-Family Kinases) SB - IM MH - Arctium/chemistry MH - Fermentation MH - Fruit/chemistry MH - Gene Expression Regulation/drug effects MH - Humans MH - Hypersensitivity/*drug therapy/immunology/pathology MH - Immunoglobulin E/*biosynthesis/immunology MH - Intracellular Signaling Peptides and Proteins/biosynthesis MH - Plant Extracts/*administration & dosage/chemistry MH - Protein-Tyrosine Kinases/biosynthesis MH - Proto-Oncogene Proteins c-fyn/biosynthesis MH - Receptors, IgE/*biosynthesis/immunology MH - Signal Transduction/drug effects MH - Syk Kinase MH - Tumor Necrosis Factor-alpha MH - src-Family Kinases/biosynthesis EDAT- 2015/12/29 06:00 MHDA- 2016/11/01 06:00 CRDT- 2015/12/29 06:00 PHST- 2015/09/03 00:00 [received] PHST- 2015/12/15 00:00 [accepted] PHST- 2015/12/29 06:00 [entrez] PHST- 2015/12/29 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] AID - 10.3892/ijmm.2015.2447 [doi] PST - ppublish SO - Int J Mol Med. 2016 Feb;37(2):501-8. doi: 10.3892/ijmm.2015.2447. Epub 2015 Dec 28.