Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Catenarin, an anthraquinone compound, inhibits CXCR4 and CCR5 pathways to protect against type 1 diabetes in NOD mice (#197)

Wen-Chin Yang 1 , Cicero L. T. Chang 2 , Shou-Hsien Huang 1 , Ming-Yi Shen 1
  1. Academia Sinica, Taipei, Taiwan
  2. Veterinary Medicine, Chung Hsin University, Taichung, Taiwan

Inflammation contributes to leukocyte migration, termed insulitis, and β cell loss in type 1 diabetes (T1D).Naturally occurring anthraquinones are claimed as anti-inflammatory compounds; however, their actions are not clear. This study aimed to investigate the effect and mechanism of catenarin on the inflammatory disease, T1D. Catenarin and/or its anthraquinone analogs dose-dependently suppressed C-X-C chemokine receptor type 4 (CXCR4)- and C-C chemokine receptor type 5 (CCR5)-implicated chemotaxis in leukocytes. Catenarin, the most potent anthraquinone tested in the study, prevented T1D in non-obese diabetic mice. Mechanistic study showed that catenarin did not act on the expression of CCR5 and CXCR4. On the contrary, catenarin inhibited CCR5- and CXCR4-mediated chemotaxis via the reduction of the phosphorylation of mitogen-activated protein kinases (p38 and JNK) and their upstream kinases (MKK6 and MKK7) and calcium mobilization. Overall, this study demonstrates the preventive effect and molecular mechanism of action of catenarin on T1D, suggesting its novel use as a prophylactic agent in T1D.

  1. Shen, M.Y., Lin, Y.P., Yang, B.C., Jang, Y.S., Chiang, C.K., Mettling, C., Chen, Z.W., Sheu, J.R., Chang, C.T.L.*, Lin, Y.L. *, and Yang, W.C.* (2012) Catenarin prevents type 1 diabetes in non-obese diabetic mice via inhibition of leukocyte migration involving the MEK6/p38 and MEK7/JNK pathways. Evidence-Based Complementary and Alternative Medicine. 982396.
  2. Chang, C.L.T., Chen, Y.C., Chen, H.M., Yang, N.S., Yang, W.C. (2013) Natural cures for type 1 diabetes: A review of phytochemicals, Biological actions, and clinical potential. Current Medicinal Chemistry. 20(7):899-907.