Inhibition of proprotein convertase subtilisin/kexin type 9: A novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia

De-liang Liu; Li-jun Xu; Hui Dong; Guang Chen; Zhao-yi Huang; Xin Zou; Kai-fu Wang; Yun-huan Luo; Fu-er Lu

doi:10.1007/s11655-014-1775-1

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Inhibition of proprotein convertase subtilisin/kexin type 9: A novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia

Updated：2021-08-27

- Inhibition of proprotein convertase subtilisin/kexin type 9: A novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia
- Chinese Journal of Integrative Medicine Vol. 21, Issue 2, Pages: 132-138(2015)
- Affiliations：
  
  1. Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan,China
  2. Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan,China
- Author bio：
- Funds：
  
  Supported by the National Natural Science Foundation of China (No. 81173370)
- DOI：10.1007/s11655-014-1775-1
  CLC：
- Published：2015，
  
  Published Online：3 June 2014，
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Liu, Dl., Xu, Lj., Dong, H. et al. Inhibition of proprotein convertase subtilisin/kexin type 9: A novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia., Chin. J. Integr. Med. 21, 132–138 (2015). https://doi.org/10.1007/s11655-014-1775-1

De-liang Liu, Li-jun Xu, Hui Dong, et al. Inhibition of proprotein convertase subtilisin/kexin type 9: A novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia. [J]. Chinese Journal of Integrative Medicine 21(2):132-138(2015)
Liu, Dl., Xu, Lj., Dong, H. et al. Inhibition of proprotein convertase subtilisin/kexin type 9: A novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia., Chin. J. Integr. Med. 21, 132–138 (2015). https://doi.org/10.1007/s11655-014-1775-1 DOI：

De-liang Liu, Li-jun Xu, Hui Dong, et al. Inhibition of proprotein convertase subtilisin/kexin type 9: A novel mechanism of berberine and 8-hydroxy dihydroberberine against hyperlipidemia. [J]. Chinese Journal of Integrative Medicine 21(2):132-138(2015) DOI： 10.1007/s11655-014-1775-1.

摘要

To investigate the effect and molecular mechanisms of different doses of 8-hydroxy dihydroberberine (Hdber) for the treatment of hyperlipidemia in rats. 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. 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. 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.

Abstract

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)

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)

关键词

8-hydroxy dihydroberberinehyperlipidemiaratlow-density lipoprotein receptor

Keywords

8-hydroxy dihydroberberinehyperlipidemiaratlow-density lipoprotein receptor

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