State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing City Key Laboratory of Drug Delivery Technology and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Nat Commun. 2019 Apr 30;10(1):1981. doi: 10.1038/s41467-019-09852-0.
Cardiovascular and metabolic disease (CMD) remains a main cause of premature death worldwide. Berberine (BBR), a lipid-lowering botanic compound with diversified potency against metabolic disorders, is a promising candidate for ameliorating CMD. The liver is the target of BBR so that liver-site accumulation could be important for fulfilling its therapeutic effect. In this study a rational designed micelle (CTA-Mic) consisting of α-tocopheryl hydrophobic core and on-site detachable polyethylene glycol-thiol shell is developed for effective liver deposition of BBR. The bio-distribution analysis proves that the accumulation of BBR in liver is increased by 248.8% assisted by micelles. Up-regulation of a range of energy-related genes is detectable in the HepG2 cells and in vivo. In the high fat diet-fed mice, BBR-CTA-Mic intervention remarkably improves metabolic profiles and reduces the formation of aortic arch plaque. Our results provide proof-of-concept for a liver-targeting strategy to ameliorate CMD using natural medicines facilitated by Nano-technology.
心血管和代谢疾病（CMD）仍然是全球范围内导致过早死亡的主要原因。小檗碱（BBR）是一种具有多种代谢紊乱作用的降脂植物化合物，是改善CMD 的有前途的候选药物。肝脏是 BBR 的作用部位，因此肝脏部位的积累对于发挥其治疗效果可能很重要。在这项研究中，设计了一种由α-生育酚疏水性核心和原位可分离的聚乙二醇-硫醇壳组成的理性胶束（CTA-Mic），以有效递送至肝脏沉积 BBR。生物分布分析证明，胶束辅助可使 BBR 在肝脏中的积累增加 248.8%。在 HepG2 细胞和体内可检测到一系列与能量相关的基因上调。在高脂肪饮食喂养的小鼠中，BBR-CTA-Mic 干预可显著改善代谢谱并减少主动脉弓斑块的形成。我们的结果为使用纳米技术改善心血管和代谢疾病的天然药物的肝脏靶向策略提供了概念验证。
