Abstract
Diabetes mellitus is a clinical syndrome characterised by hyperglycaemia; its complications lead to disability and even death. Semen Cassiae is a traditional Chinese medicine, which has anti-hypertensive, anti-hyperlipidaemia, anti-oxidation, and anti-ageing properties. Our study was designed to evaluate the action of total anthraquinones of Semen Cassiae extract (SCE) on the improvement of glucose metabolism in diabetic rats and to elucidate the underlying mechanism. First, we evaluated the effect of SCE on normal rats. Next, we observed the effect of SCE using a rat model of diabetes, which was established by feeding rats with high-energy diet for 4 weeks and a single intraperitoneal injection of streptozotocin (STZ; 30 mg/kg) 3 weeks after starting the high-energy diet. Rats in different SCE groups (administered 54, 108, and 324 mg/kg/day of SCE) and metformin group (162 mg/kg/day, positive control drug) were treated with the corresponding drugs 1 week before starting high-energy diet and treatment continued for 5 weeks; meanwhile, rats in the control group were administered the same volume of sodium carboxymethyl cellulose solution (vehicle solution). One week after STZ injection, fasting blood glucose (FBG), oral glucose tolerance (OGT), fasting serum insulin (FSI) and serum lipids were quantified. Finally, the expression of proteins in the phosphatidylinositol-3-kinase (PI3K)–Akt–AS160–glucose transporter isoform 4 (GLUT4) signalling pathway was detected by western blotting. The data indicated that the levels of FBG and serum lipids were significantly lowered, and OGT and FSI were markedly increased in diabetic rats treated with SCE (108 mg/kg/day); however, SCE did not cause hypoglycaemia in normal rats. The molecular mechanisms were explored in the skeletal muscle. SCE markedly restored the decreased translocation of GLUT4 in diabetic rats. Moreover, the protein expressions of phosphorylated-AS160 (Thr642), phosphorylated-Akt (Ser473) and PI3K were significantly increased after SCE treatment in the skeletal muscle. These results indicate that SCE exerts an anti-hyperglycaemic effect by promoting GLUT4 translocation through the activation of the PI3K–Akt–AS160 signalling pathway. Our findings suggest that treatment with SCE, containing anthraquinones, could be an effective approach to enhance diabetes therapy.
Highlights
Diabetes mellitus has become a global public health problem
The current study aimed to evaluate whether the alcohol extract from Semen Cassiae has an antihyperglycaemic effect in rats with diabetes mellitus (DM) and to explore the possible underlying mechanisms
We found that Semen Cassiae extract (SCE) containing anthraquinones is effective in lowering blood glucose (BG) in diabetic rats and promoting glucose uptake by inducing the translocation of glucose transporter isoform 4 (GLUT4) in skeletal muscle through the activation of the
Summary
Diabetes mellitus has become a global public health problem. In 2015, the total number of adults worldwide suffering from DM was 415 million and every 6 s a person died from DM (5 million deaths); this includes 109.6 million people in the People’s Republic of China (ranking first in the number of diabetes patients). By 2040, 642 million adults will have diabetes and the number in China will be 150 million (International Diabetes Federation, 2015). A persistently high level of BG can lead to serious complications, including damage to the hearts, blood vessels, kidneys, eyes, and nerves. DM and its complications impose an enormous burden on medical costs. This is an urgent problem for medical scientists all over the world, including China. Many clinical trials have confirmed that the positive interventions during the early period of DM to improve glucose tolerance and FBG could effectively postpone and reduce the development from prediabetes into type 2 DM (Knowler et al, 2002; DeFronzo and Abdul-Ghani, 2011; Perreault et al, 2012)
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