Inhibitory effects of sesquiterpene lactones isolated from Eupatorium chinense

详细信息    查看全文

• 作者：Tomohiro Itoh ; Masayoshi Oyama ; Norihiko Takimoto ; Chihiro Kato ; Yoshinori Nozawa ; Yukihiro Akao ; Munekazu Iinuma
• 关键词：Allergy ; Rat basophilic leukemia RBL-2H3 cells ; Sesquiterpene lactone ; degranulation ; Eupatorium chinense L.
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2009
• 出版时间：15 April 2009
• 年：2009
• 卷：17
• 期：8
• 页码：3189-3197
• 全文大小：3040 K

文摘

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.