Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver

Molecules

Takako Yokozawa¹  KyoungMi Moon²  HaeYoung Chung²  MinJo Kim²  HyoungOh Jeong²  Bonggi Lee²  Jiwon Jeong²  DaeHyun Kim² 

[1] Graduate School of Science and Engineering for Research, University of Toyama, Toyama 930-8555, Japan;Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735, Korea;

关键词: magnesium lithospermate B;    PPARβ/δ;    ER stress;    insulin resistance;    inflammasome;    aging;   

DOI  :  10.3390/molecules23092098

来源: DOAJ

【 摘 要 】

Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction of Salvia miltiorrhiza. Magnesium lithospermate B exhibits various biological functions, including antidiabetic, neuroprotective, and antioxidant effects. However, its beneficial effects on insulin sensitivity and related signaling pathways in the liver need to be elucidated. Our previous study reported that MLB is a PPARβ/δ agonist in fibroblasts. Because insulin-sensitizing and anti-inflammatory effects of PPARβ/δ has been reported in the liver, we investigated whether MLB has a beneficial effect on insulin-, ER stress- and inflammasome-related signaling in the livers of aging and obese animal models. Western blotting and protein-ligand docking simulation showed that MLB activated PPARβ/δ and improved glucose tolerance in the livers of aging and obese animal models. MLB supplementation ameliorated aging or obesity-induced disruption of insulin signaling in the liver. Consistently, aging and obesity-induced increase in the protein levels of a gluconeogenic phosphoenolpyruvate carboxykinase was decreased by MLB. When molecular signaling pathways related to insulin signaling were examined in the liver, MLB supplementation suppressed ER stress- and inflammasome-related signaling molecules induced by aging and obesity. These results suggest that MLB may improve insulin resistance in the liver at least partially by suppressing ER stress and inflammasome formation in aging and obese animal models.

【 授权许可】

Unknown