Department of Clinical immunology, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
Int J Mol Sci. 2018 Dec 6;19(12):3903. doi: 10.3390/ijms19123903.
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 ( < 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.
天然化合物黄连素已被报道具有抗糖尿病活性，并改善紊乱的脂质代谢。在我们之前的研究中，我们发现这些化合物上调了沉默调节蛋白 1 的表达——这是热量限制的关键分子，因此，研究黄连素与沉默调节蛋白 1 激活剂白藜芦醇的联合降脂活性是非常有趣的。我们的结果表明，黄连素与白藜芦醇联合使用在高脂饮食诱导的小鼠中具有增强的降血脂作用，并能够将脂肪细胞中的脂质积累降低到显著低于单药治疗的水平。在高脂饮食诱导的高血脂小鼠中，联合使用黄连素（30mg/kg/天，口服）和白藜芦醇（20mg/kg/天，口服）可使血清总胆固醇降低 27.4%±2.2%，低密度脂蛋白胆固醇降低 31.6%±3.2%，比白藜芦醇（8.4%±2.3%，6.6%±2.1%）或黄连素（10.5%±1.95%，9.8%±2.58%）单药治疗更有效（均<0.05）。在 3T3-L1 脂肪细胞中，用 12μmol/L 或 20μmol/L 黄连素联合 25μmol/L 白藜芦醇处理可观察到脂质积累的抑制作用更明显，比单独使用两种化合物更为显著。此外，白藜芦醇可以增加肝 L02 细胞内黄连素的含量。此外，与单独使用化合物相比，黄连素与白藜芦醇联合使用可显著增加 HepG2 细胞中低密度脂蛋白受体的表达，使其表达水平提高约一倍。这些结果表明，黄连素与白藜芦醇联合使用降低血脂的增强作用可能与低密度脂蛋白受体的上调有关，可能是肥胖相关疾病（如 2 型糖尿病和代谢综合征）中高脂血症的有效治疗方法。
