The intestinal absorption of berberine(Ber) and its structural modified compound 8-hydroxy dihydroberberine(Hdber) was compared, and their effects on the intestinal absorption of sugar by perfusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography(HPLC) was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than 10%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 μg/mL. However, Hdber presented stronger activity than Ber(P<0.01). It is suggested that Hdber is absorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.
Objective:To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine(Hdber) for the treatment of hyperlipidemia in rats.Methods: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-A Ⅰ) 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.Results:Compared with the control group of rats,the model group demonstrated a deteriorated blood lipid profile and exhibited increased expression levels of PCSK-9protein in their liver tissues(P<0.01).In addition,the high-fat diet decreased the expression levels of LDL-R,SREBP-2and 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.Conclusions:Hdber is effective in the treatment of hyperlipidemia in ra
