Inhibition of proprotein convertase subtilisin/kexin type 9: a novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia.
Chin J Integr Med
; 21(2): 132-8, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-24893659
ABSTRACT
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-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.RESULTS:
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.CONCLUSIONS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Berberina
/
Serina Endopeptidases
/
Hiperlipidemias
Limite:
Animals
Idioma:
En
Revista:
Chin J Integr Med
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China