TanshinoneⅡA phenanthroimidazole derivative polarizes macrophage to improve metabolic homeostasis.

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.

• Authors: Lei Ma, Shiya Luo, Lin Zhou, Zewei Zhao, Qiao Li, Lin Xu, Baoyong Gong, Weiwei Qi, Ti Zhou, Xia Yang, Guoquan Gao, Wenjie Mei, Zhonghan Yang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 514 Issue 3 Pg. 861-867 (06 30 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31084927 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Abietanes
• Anti-Obesity Agents
• Blood Glucose
• Cytokines
• Fatty Acids, Nonesterified
• Hypoglycemic Agents
• Insulin
• Phenanthrenes
• tanshinone

Topics

• Abietanes (chemistry, pharmacology)
• Adipose Tissue (drug effects, metabolism, pathology)
• Animals
• Anti-Obesity Agents (chemistry, pharmacology)
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Cell Differentiation (drug effects)
• Cell Polarity (drug effects)
• Cytokines (blood)
• Diabetes Mellitus, Experimental (blood, drug therapy, genetics, pathology)
• Diet, High-Fat (adverse effects)
• Fatty Acids, Nonesterified (blood)
• Humans
• Hypoglycemic Agents (chemistry, pharmacology)
• Insulin (blood)
• Insulin Resistance
• Macaca fascicularis
• Macrophage Activation (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (blood, drug therapy, etiology, genetics)
• Phenanthrenes (chemistry, pharmacology)
• RAW 264.7 Cells