Berberine-loaded solid lipid nanoparticles are concentrated in the liver and ameliorate hepatosteatosis in db/db mice

• Published in: International journal of nanomedicine Vol. 10; no. default; pp. 5049 - 5057
• Main Authors: Xue, Mei, Zhang, Liang, Yang, Ming-xing, Zhang, Wei, Li, Xiu-min, Ou, Zhi-min, Li, Zhi-peng, Liu, Su-huan, Li, Xue-jun, Yang, Shu-yu
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2015; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Alanine Transaminase - blood; Animals; Aspartate Aminotransferases - blood; berberine; Berberine - blood; Berberine - chemistry; Berberine - pharmacology; Bioavailability; Body Weight - drug effects; Care and treatment; Carnitine O-Palmitoyltransferase - genetics; Carnitine O-Palmitoyltransferase - metabolism; Chinese medicine; Chromatography; Diabetes; Disease Models, Animal; Down-Regulation; Drug delivery systems; Drug dosages; Drugs; Fatty Acid Synthases - genetics; Fatty Acid Synthases - metabolism; Fatty acids; Fatty Acids, Nonesterified - blood; fatty liver; Fatty Liver - drug therapy; Glucose; hepatosteatosis; Homeostasis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Innovations; Insulin resistance; Inventors; Kinases; Lipid Metabolism - drug effects; Lipids; Lipids - chemistry; Liver - drug effects; Liver - metabolism; Liver diseases; Male; Medical research; Metabolism; Mice; Nanoparticles; Nanoparticles - chemistry; Obesity; Organ Size - drug effects; Original Research; Polymerase chain reaction; Proteins; solid lipid nanoparticles; Stearoyl-CoA Desaturase - chemistry; Stearoyl-CoA Desaturase - pharmacology; Sterol Regulatory Element Binding Protein 1 - genetics; Sterol Regulatory Element Binding Protein 1 - metabolism; Sterols; Triglycerides - metabolism; Up-Regulation; Vehicles; Beijing China; United States > US; China; fatty liver; hepatosteatosis; solid lipid nanoparticles; berberine
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S84565

Berberine (BBR) shows very low plasma levels after oral administration due to its poor absorption by the gastrointestinal tract. We have previously demonstrated that BBR showed increased gastrointestinal absorption and enhanced antidiabetic effects in db/db mice after being entrapped into solid lipid nanoparticles (SLNs). However, whether BBR-loaded SLNs (BBR-SLNs) also have beneficial effects on hepatosteatosis is not clear. We investigated the effects of BBR-SLNs on lipid metabolism in the liver using histological staining and reverse transcription polymerase chain reaction analysis. The results showed that oral administration of BBR-SLNs inhibited the increase of body weight and decreased liver weight in parallel with the reduction of serum alanine transaminase and liver triglyceride levels in db/db mice. The maximum drug concentration in the liver was 20-fold higher than that in the blood. BBR-SLNs reduced fat accumulation and lipid droplet sizes significantly in the liver, as indicated by hematoxylin and eosin and Oil Red O staining. The expression of lipogenic genes, including fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD1), and sterol regulatory element-binding protein 1c (SREBP1c) were downregulated, while lipolytic gene carnitine palmitoyltransferase-1 (CPT1) was upregulated in BBR-SLN-treated livers. In summary, we have uncovered an unexpected effect of BBR-SLNs on hepatosteatosis treatment through the inhibition of lipogenesis and the induction of lipolysis in the liver of db/db mice.