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Int J Mol Sci. 2018 Dec 6;19(12). pii: E3903. doi: 10.3390/ijms19123903.

Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy.

Zhu X1,2,3, Yang J4,5, Zhu W6, Yin X7,8, Yang B9, Wei Y10, Guo X11.

Author information

1
Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China. zhuxf@xxmu.edu.cn.
2
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China. zhuxf@xxmu.edu.cn.
3
Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Medical University, Xinxiang 453003, China. zhuxf@xxmu.edu.cn.
4
Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China. yjy289688354@163.com.
5
Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Medical University, Xinxiang 453003, China. yjy289688354@163.com.
6
Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China. zzwwjj0304@163.com.
7
Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China. xiao143134@163.com.
8
Henan Key Laboratory of Immunology and Targeted Drugs, Xinxiang Medical University, Xinxiang 453003, China. xiao143134@163.com.
9
Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China. ybbcyh@163.com.
10
Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China. weiyihui1@163.com.
11
Department of Microbiology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China. guoxiaofang_1981@126.com.

Abstract

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1-a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (30 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.

KEYWORDS:

berberine; high fat diet; low-density-lipoprotein receptor; resveratrol; sirtuin 1

PMID:
30563192
PMCID:
PMC6321535
DOI:
10.3390/ijms19123903
[Indexed for MEDLINE]
Free PMC Article

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