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标题：Induction of Apoptosis in Human Lung Fibroblasts and Peripheral Lymphocytes in Vitro by Shosaiko-to Derived Phenolic Metabolites
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作者：Zhen-Li Liu ; Sachiko Tanaka ; Hiroshi Horigome 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2002
卷号：25
期号：1
页码：37-41
DOI：10.1248/bpb.25.37
出版社：The Pharmaceutical Society of Japan
摘要：Shosaiko-to is a Kampo medicine used for the treatment of chronic hepatitis in Japan. Lately, over 200 cases of interstitial pneumonia have been reported resulting from Shosaiko-to therapy, and the number of cases increased when patients were administrated interferon (IFN)-α at the same time. However, the mechanisms of this Shosaiko-to implicated interstitial pneumonia are not fully understood. In this study, we examined by flow cytometry analysis the in vitro effects of 7 phenolic compounds (lignans and flavonoids), which were detected from human urine after administration of Shosaiko-to, and IFN-α on inducing apoptosis in human lung fibroblasts and peripheral blood mononuclear cells (PBMCs). Among the 7 compounds, baicalein and medicarpin (10 µg/ml) showed significant apoptosis-inducing effects on human PBMCs. In human lung fibroblasts, medicarpin exhibited a significantly higher activity to induce apoptosis compared to the control, and the percentage of cells undergoing apoptosis showed time- and dose-dependent increases. Baicalein (0.1 and 1 µg/ml), liquiritigenin (10 µg/ml) and davidigenin (10 µg/ml) also showed significant effects after 96 h treatment. Whereas, baicalin, oroxylin A and wogonin did not show any effect on inducing apoptosis in PBMCs and fibroblasts. Baicalein and medicarpin significantly inhibited the growth and reduced the viability of lung fibroblasts. IFN-α had no apoptosis-inducing effect, and it did not show synergistic interaction with any of the compounds derived from Shosaiko-to on inducing apoptosis in both human lung fibroblasts and PBMCs. These results suggested that phenolic compounds found in human post-administrative urine of Shosaiko-to, especially baicalein and medicarpin, exhibited a direct effect on human lung fibroblasts and immune cells to induce apoptosis.
关键词：shosaiko-to;human lung fibroblast;apoptosis;human peripheral lymphocyte;phenolic compound