ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine (Hdber) for the treatment of hyperlipidemia in rats.</p><p><b>METHODS</b>A rat model of hyperlipidemia was established by feeding rats a high-fat diet for 4 weeks in 70 rats of 80 animals, and 10 rats were randomly selected as control group. The hyperlipidemic rats were then randomly divided into the following groups: a model group (MOD); a berberine group [BBR, 156 mg/(kg day)]; Hdber groups, which were treated with different doses of Hdber [78, 39 and 19.5 mg/(kg day)]; and a simvastatin group [SIM, 4 mg/(kg day)]. The corresponding therapy was administered to the rats of each treatment via gastric tubes. Normal animals were used as a control group. The blood levels of various lipids, including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acid (FFA), apolipoprotein AI(Apo-AI) and apolipoprotein B (Apo-B) were examined. The protein expressions of low-density lipoprotein receptor (LDL-R), sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and proprotein convertase subtilisin/kexin type 9 (PCSK-9) in liver tissues were determined by Western blot analysis.</p><p><b>RESULTS</b>Compared with the control group of rats, the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9 protein in their liver tissues (P<0.01). In addition, the high-fat diet decreased the expression levels of LDL-R, SREBP-2 and HMGCR proteins in murine liver tissues. However, the addition of berberine or Hdber reversed the blood lipid profile changes (P<0.05 or P<0.01), decreased the expression levels of PCSK-9 proteins (P<0.01), and increased the expression levels of LDL-R proteins in the hyperlipidemic rats (P<0.01). These compounds did not significantly influence the expression levels of SREBP-2 and HMGCR proteins in the hyperlipidemic rats.</p><p><b>CONCLUSIONS</b>Hdber is effective in the treatment of hyperlipidemia in rats. The therapeutic mechanisms of Hdber may be associated with increasing the expression of LDL-R protein and decreasing the expression of PCSK-9 protein in liver tissues.</p>
Subject(s)
Animals , Male , Apolipoprotein A-I , Blood , Apolipoproteins B , Blood , Berberine , Pharmacology , Therapeutic Uses , Hydroxymethylglutaryl CoA Reductases , Metabolism , Hyperlipidemias , Blood , Drug Therapy , Lipids , Blood , Liver , Metabolism , Proprotein Convertase 9 , Rats, Wistar , Receptors, LDL , Metabolism , Serine Endopeptidases , Metabolism , Sterol Regulatory Element Binding Protein 2 , MetabolismABSTRACT
The effect of Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats was investigated. The rat model of type 2 diabetes was established by feeding on a high-fat diet for 8 weeks and by subsequently intravenous injection of small doses of streptozotocin. Rats in treatment groups, including the Fructus Mume formula treatment group (FM), the cold property herbs of Fructus Mume formula treatment group (CFM), the warm property herbs of Fructus Mume formula treatment group (WFM), were administrated with Fructus Mume formula and its separated prescription extract by gavage, while the rats in diabetic model group (DM) and metformin group (MET) were given by gavage with normal saline and metformin correspondingly. The body weight before and after treatment was measured, and the oral glucose tolerance test (OGTT) and the insulin release test (IRT) were performed. The homeostasis model assessment-insulin resistance index (HOMA-IR) was calculated. The protein and mRNA expression levels of Insr, β-arrestin-2, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were detected by using Western blotting and RT-PCR respectively. The results demonstrated that, as compared with DM group, OGTT, IRT (0 h, 1 h) levels and HOMR-IR in treatment groups were all reduced, meanwhile their protein and mRNA expression levels of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were obviously increased, and their protein and mRNA expression levels of β-arrestin-2 in the liver and skeletal muscle tissues were also markedly increased. It was suggested that the Fructus Mume formula and its separated prescription extracts could effectively improve insulin resistance in type 2 diabetic rats, which might be related to the up-regulated expression of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues, and β-arrestin-2 in the liver and skeletal muscle tissues.
ABSTRACT
The effect of Fructus Mume formula and its separated prescription extract on insulin resistance in type 2 diabetic rats was investigated. The rat model of type 2 diabetes was established by feeding on a high-fat diet for 8 weeks and by subsequently intravenous injection of small doses of streptozotocin. Rats in treatment groups, including the Fructus Mume formula treatment group (FM), the cold property herbs of Fructus Mume formula treatment group (CFM), the warm property herbs of Fructus Mume formula treatment group (WFM), were administrated with Fructus Mume formula and its separated prescription extract by gavage, while the rats in diabetic model group (DM) and metformin group (MET) were given by gavage with normal saline and metformin correspondingly. The body weight before and after treatment was measured, and the oral glucose tolerance test (OGTT) and the insulin release test (IRT) were performed. The homeostasis model assessment-insulin resistance index (HOMA-IR) was calculated. The protein and mRNA expression levels of Insr, β-arrestin-2, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were detected by using Western blotting and RT-PCR respectively. The results demonstrated that, as compared with DM group, OGTT, IRT (0 h, 1 h) levels and HOMR-IR in treatment groups were all reduced, meanwhile their protein and mRNA expression levels of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were obviously increased, and their protein and mRNA expression levels of β-arrestin-2 in the liver and skeletal muscle tissues were also markedly increased. It was suggested that the Fructus Mume formula and its separated prescription extracts could effectively improve insulin resistance in type 2 diabetic rats, which might be related to the up-regulated expression of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues, and β-arrestin-2 in the liver and skeletal muscle tissues.