Abstract

Macrophages  infiltrated in adipose tissue play a key role in obesity. Some  traditional pharmaceutical compounds may shift the polarization of  recruited macrophages to improve metabolic homeostasis. TanshinoneⅡA  (TAN2A) is a major active component of Salvia miltiorrhiza, a  traditional anti-inflammatory cardiovascular medicine. In our study, we  firstly constructed a phenanthroimidazole derivative of TAN2A named  TAN20 by chemical synthesis, then identified its structure by  chromatography and hydrogen spectroscopy, and finally examined its  effects on immunometabolic responses. We found that TAN20 significantly  induced the alternatively-activated (M2) rather than the  classically-activated macrophages (M1), mainly through releasing the  type II cytokines. Such effects were more pronounced than that from  TAN2A. Compared to TAN2A, TAN20 substantially reduced body weight,  decreased serum free fatty acid and HOMA-IR, and increased insulin  sensitivity in obesity-induced diabetic mice. These effects of TAN20  were further validated on diabetic cynomolgus monkeys, which are closer  to human physiological conditions. Taken together, our findings  explicitly showed that TAN20 significantly polarized the macrophage and  improved metabolic homeostasis in obesity-induced diabetic models,  suggesting that TAN20 may be a potential drug against diabetes and  obesity.