Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases

• Published in: Nature communications Vol. 10; no. 1; pp. 1981 - 16
• Main Authors: Guo, Hui-Hui, Feng, Chen-Lin, Zhang, Wen-Xuan, Luo, Zhi-Gang, Zhang, Hong-Juan, Zhang, Ting-Ting, Ma, Chen, Zhan, Yun, Li, Rui, Wu, Song, Abliz, Zeper, Li, Cong, Li, Xiao-Lin, Ma, Xiao-Lei, Wang, Lu-Lu, Zheng, Wen-Sheng, Han, Yan-Xing, Jiang, Jian-Dong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.04.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 38/1; 38/35; 38/5; 38/77; 38/89; 59/5; 639/925/352/152; 64/60; 692/698/2741/288; 692/699/75/2099; 82/16; 82/80; Accumulation; Animals; Aortic arch; Berberine; Berberine - pharmacology; Bioavailability; Caco-2 Cells; Cardiovascular Diseases - blood; Cardiovascular Diseases - drug therapy; Dyslipidemias - blood; Dyslipidemias - drug therapy; Gene expression; Hep G2 Cells; High fat diet; Humanities and Social Sciences; Humans; Hydrophobicity; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Lipid Metabolism - drug effects; Lipids; Liver; Liver - drug effects; Liver - metabolism; Magnetic Resonance Spectroscopy; Male; Metabolic Diseases - blood; Metabolic Diseases - drug therapy; Metabolic disorders; Metabolism; Mice; Micelles; multidisciplinary; Nanotechnology; Nanotechnology - methods; Polyethylene glycol; Science; Science (multidisciplinary); Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• ISSN: 2041-1723; 2041-1723
• 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. Berberine has lipid-lowering effects and other metabolic benefits, but it presents with poor bioavailability. Here the authors conjugate berberine to liver-targeting nanoparticles, and show increased accumulation of berberine in the liver, improved metabolic profiles and reduced atherosclerotic plaques in mice.