Vol. 288, Issue 2, 529-534, February 1999

Novel Terpenoid-Type Quinones Isolated from Pycnanthus angolensis of Potential Utility in the Treatment of Type 2 Diabetes

Jian Luo, Jeanne Cheung, Eileen M. Yevich, John P. Clark, Joyce Tsai, Priscilla Lapresca, Rosa P. Ubillas, Diana M. Fort, Thomas J, Carlson, Richard F. Hector, Steven R. King, Christopher D. Mendez, S. D. Jolad and Gerald M. Reaven

Shaman Pharmaceuticals, Inc., South San Francisco, California

Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP-18905 are terpenoid-type quinones that significantly lowered plasma glucose concentration (p < .05) when given orally to either ob/ob or db/db mice, both of which are hyperglycemic and hyperinsulinemic. The antihyperglycemic actions of SP-18904 and SP-18905 were associated with significant decreases in plasma insulin concentrations (p < .05), suggesting that both compounds lowered glucose by enhancing insulin-mediated glucose uptake. This was supported by the insulin suppression test in ob/ob mice. Studies in hyperglycemic, insulin-deficient mice and in vitro experiments on 3T3-L1 adipocytes further supported this conclusion. As such, these two terpenoid-type quinones represent a new class of compounds of potential use in the treatment of type 2 diabetes.