title: Inhibitory effect of fermented Arctium lappa fruit extract on the IgE-mediated allergic response in RBL‑2H3 cells.
abstract: 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 β-hexosaminidase, a key biomarker of degranulation during an allergic reaction, and the production of pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) in the cells treated with or without the above-mentioned extracts. AFE weakly inhibited the release of β-hexosaminidase, whereas F-AFE significantly suppressed the release of β-hexosaminidase in a dose-dependent manner. Consistently, F-AFE suppressed the production of TNF-α and PGE2 in a dose-dependent manner. F-AFE exerted an inhibitory effect on the production of β-hexosaminidase, TNF-α and PGE2 with an IC50 value of 30.73, 46.96 and 36.27 µg/ml, respectively. Furthermore, F-AFE inhibited the phosphorylation of Lyn, Fyn and Syk, which are involved in the FcεRI signaling pathway, that of phosphoinositide phospholipase C (PLC)γ1/2 and protein kinase C (PKC)δ, 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 FcεRI receptor induced by the antigen‑IgE complex. Such effects may provide further information for the development of a phytomedicine for allergic diseases.
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea.
authors.forename: Jae-Myung
authors.initials: JM
authors.lastname: Yoo
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea.
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea.
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Daegu 41062, Republic of Korea.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
mesh_terms: D031170:Arctium / Q000737:chemistry; D005285:Fermentation; D005638:Fruit / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D051076:Proto-Oncogene Proteins c-fyn / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha; D019061:src-Family Kinases / Q000096:biosynthesis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010936:Plant Extracts; D017455:Receptors, IgE; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases