Salvianolic Acid B Inhibited PPARγ Expression and Attenuated Weight Gain in Mice with High-Fat Diet-Induced Obesity

Abstract

Background/Aims: Obesity contributes to the development of cardiometabolic disorders such as type 2 diabetes, fatty liver disease and cardiovascular disease. Salvianolic acid B (Sal B) is a molecule derived from the root of Salvia miltiorrhiza (Danshen), which is a traditional Chinese medicine that is widely used to treat cardiovascular diseases. However, the role of Sal B in obesity and obesity-related metabolic disorders is unknown. In this study, we aimed to investigate the effects of Sal B on high-fat diet-induced obesity and determine the possible mechanisms involved. Methods: Male C57BL/6J mice fed a high-fat diet for 12 weeks received a supplement of Sal B (100 mg/kg/day) by gavage for a further 8 weeks. These mice were compared to control mice fed an un-supplemented high-fat diet. 3T3-L1 preadipocytes were used in vitro studies. Results: Sal B administration significantly decreased body weight, white adipose tissue weight, adipocyte size and lipid (triglyceride and total cholesterol) levels in obese mice. Eight weeks of Sal B administration also improved the intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) scores in high-fat diet-induced obese mice. In 3T3-L1 preadipocytes that were cultured in vitro and induced to differentiate, Sal B reduced the accumulation of lipid droplets and lipid content in a dose-dependent manner. Immunoblotting indicated that Sal B decreased peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) expression but increased the expression of GATA binding protein 2 and 3 (GATA 2, GATA 3) both in vivo and in vitro. Conclusion: Our data suggest that Sal B may reduce obesity and obesity-related metabolic disorders by suppressing adipogenesis. The effects of Sal B in adipose tissue may be related to its action on PPARγ, C/EBPα, GATA-2 and GATA-3.

Salvianolic Acid B Ameliorates Hyperglycemia and Dyslipidemia in db/db Mice through the AMPK Pathway

“…Although its most common use is in the treatment of cardio-cerebral vascular diseases [14][15][16], Sal B is recently reported to possess a number of potential implications in the treatment of insulin resistance, obesity, and type 2 diabetes [17][18][19][20]. Sal B or Salvia miltiorrhiza extract improved glycemic control, dyslipidemia, and insulin sensitivity in high fat diet and streptozocin-induced type 2 diabetic rats [17,19].…”

Borrelidin Isolated from <i>Streptomyces</i> sp. Inhibited Adipocyte Differentiation in 3T3-L1 Cells <i>via</i> Several Factors Including GATA-Binding Protein 3

“…The IC 50 value of borreldin (0.25 µM) was lower than those of known lipid accumulation inhibitors, berberine (approx. 2.0 µM) and salvianolic acid B (over 100 µM), 21,22) and borrelidin is probably more potent than these inhibitors. Berberine and salvianolic acid B exhibited anti-obesity effect in vivo using KK-Ay mice and high-fat dietinduced obesity mice, respectively.…”

“…Berberine and salvianolic acid B exhibited anti-obesity effect in vivo using KK-Ay mice and high-fat dietinduced obesity mice, respectively. 26,22) The accumulation of intracellular lipids has been used as a marker of adipocyte differentiation. 27) Effects of borrelidin on differentiation were evaluated by measuring the mRNA expression of adipocyte-specific genes, FABP4, LPL, HSD11β1 and GLUT4 (Fig.…”

“…GATA-2 and GATA-3 appear to act as gatekeepers to block expression of PPARγ and the role of GATA-3 was clarified using GATA-3 knockout ES cells, 19) which support studying GATA-2 and GATA-3 as suitable targets to inhibit adipocyte differentiation. Recently, berberine and salvianolic acid B were reported to up-regulate GATA-2 and GATA-3 expression during inhibition of 3T3-L1 adipocyte differentiation, 21,22) although the role of GATA-2 or GATA-3 was not defined in these reports.…”

Salvianolic Acid B Ameliorates Cognitive Deficits Through IGF-1/Akt Pathway in Rats with Vascular Dementia

“…A large number of research have been used SalB to treat cardiovascular diseases [7, 8]. Recently, SalB is demonstrated effective in diabetic rats, obesity for its role of regulating glucose and lipid metabolism [9, 10]. SalB is also widely used in diseases of nervous system.…”