Inhibitory effects of sesquiterpene lactones isolated from Eupatorium chinense L. on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice |
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Authors: | Tomohiro Itoh Masayoshi Oyama Norihiko Takimoto Chihiro Kato Yoshinori Nozawa Yukihiro Akao Munekazu Iinuma |
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Affiliation: | 1. Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan;2. Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan |
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Abstract: | Sesquiterpene lactones (SQTLs) have been shown to suppress the degranulation as inferred by histamine release in rat basophilic leukemia RBL-2H3 cells. In this study, we isolated the 9 kinds of SQTLs from Eupatorium chinense L. and examined the effects of these SQTLs on the degranulation in RBL-2H3 cells. The chemical structures of two novel compounds (SQTL-3 and 8) were determined. All the SQTLs suppressed the degranulation from Ag-stimulated RBL-2H3 cells. To disclose the inhibitory mechanism of degranulation by SQTLs, we examined the activation of intracellular signaling molecules such as Lyn, Syk, and PLCγs and intracellular free Ca2+ concentration ([Ca2+]i). None of these SQTLs showed the activation of Syk and PLCγs. The intracellular free Ca2+ concentration ([Ca2+]i) was elevated by FcεRI activation, but SQTLs treatment reduced the elevation of [Ca2+]i by suppressing Ca2+ influx. Thus, it was suggested that the suppression of Ag-stimulated degranulation by these SQTLs is mainly due to the decreased Ca2+ influx.Furthermore, in order to clarify the in vivo effect of SQTL-rich extract, we administered SQTL-rich extract to the type I allergic model mice and measured the passive cutaneous anaphylaxis (PCA) reaction induced by IgE-antigen complex. The SQTLs remarkably suppressed PCA reaction in a dose-dependent manner. Thus, it was suggested that SQTLs would be a candidate as an anti-allergic agent. |
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