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Cytopiloyne, a Polyacetylenic Glucoside, Prevents Type 1 Diabetes in Nonobese Diabetic Mice¹

Cicero Lee-Tian Chang^*,, Shu-Lin Chang^*,, Yi-Mei Lee^*, Yi-Ming Chiang^*, Da-Yung Chuang^*,, Hui-Kai Kuo^* and Wen-Chin Yang^2,*,

^* Agricultural Biotechnology Research Center, Academia Sinica, Taiwan, Republic of China; Department of Biological Science and Technology, National Chiao Tung University, Taiwan, Republic of China; and Department of Veterinary Medicine/Department of Life Science, National Chung Hsing University, Taiwan, Republic of China

Some polyacetylenes from the plant Bidens pilosa have been reported to treat diabetes. In this study, we report that the cytopiloyne from B. pilosa, which is structurally different from the above-mentioned polyacetylenes and inhibits CD4⁺ T cell proliferation, effectively prevents the development of diabetes in nonobese diabetic mice as evidenced by a normal level of blood glucose and insulin and normal pancreatic islet architecture. Cytopiloyne also suppresses the differentiation of type 1 Th cells but promotes that of type 2 Th cells, which is consistent with it enhancing GATA-3 transcription. Also, long-term application of cytopiloyne significantly decreases the level of CD4⁺ T cells inside pancreatic lymph nodes and spleens but does not compromise total Ab responses mediated by T cells. Coculture assays imply that this decrease in CD4⁺ T cells involves the Fas ligand/Fas pathway. Overall, our results suggest that cytopiloyne prevents type 1 diabetes mainly via T cell regulation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants (NSC91-2320-B-001-056, NSC92-2320-B-001-034, NSC93-2320-B-001-008, and 94F002-2) from the National Science Council and Academia Sinica, Taiwan, Republic of China.

² Address correspondence and reprint requests to Dr. Wen-Chin Yang, Agricultural Biotechnology Research Center, Academia Sinica, 128, Academia Road, Section 2, Nankang 115, Taipei, Taiwan, Republic of China. E-mail address: wcyang{at}gate.sinica.edu.tw

³ Abbreviations used in this paper: FasL, Fas ligand; AU, arbitrary unit.