Abstract
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.
Highlights
Aging represents the accumulation of changes in a human being over time, encompassing physical, psychological, and social changes
Stress and improve insulin sensitivity. It was not directly examined in our study whether or not the Magnesium lithospermate B (MLB)-mediated amelioration of aging or obesity-induced endoplasmic reticulum (ER) stress, inflammasome formation, and disrupted insulin signaling are mediated through activating PPARβ/δ or through different mechanisms independent of PPARβ/δ
Other studies showed that PPARβ/δ agonist notably decreased insulin resistance, ER stress, and inflammasome [31,32,33,34]
Summary
Aging represents the accumulation of changes in a human being over time, encompassing physical, psychological, and social changes. Age-related diseases include diabetes, cancer, arthritis, dementia, vascular diseases, obesity, and metabolic syndrome [1]. The aging population has an increased incidence of diabetes and obesity, which are closely associated with insulin resistance [2]. Obesity is closely associated with metabolic syndrome, leading to reduced life span by increasing a risk of various diseases including stroke, diabetes, cardiovascular diseases, and cancers [3]. It is one of the most serious public health problems of the 21st century associated with aging [4]. Managing obesity-related metabolic syndrome including insulin resistance, dyslipidemia, and fatty liver may be an important strategy to ameliorate aging-related disorders
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