Tanshinoneâ
¡A phenanthroimidazole derivative polarizes macrophage to improve metabolic homeostasis.
Biochem Biophys Res Commun
; 514(3): 861-867, 2019 06 30.
Article
em En
| MEDLINE
| ID: mdl-31084927
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. Tanshinoneâ
¡A (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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenantrenos
/
Tecido Adiposo
/
Fármacos Antiobesidade
/
Abietanos
/
Diabetes Mellitus Experimental
/
Hipoglicemiantes
/
Obesidade
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China