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

Authors Xue M, Zhang L, Yang M, Zhang W, Li X, Ou Z, Li Z, Liu S, Li X, Yang S

Received 13 March 2015

Accepted for publication 11 May 2015

Published 6 August 2015 Volume 2015:10(1) Pages 5049—5057

DOI https://doi.org/10.2147/IJN.S84565

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Lei Yang

Mei Xue,1,2,* Liang Zhang,3,* Ming-xing Yang,1 Wei Zhang,1 Xiu-min Li,1,2 Zhi-min Ou,1 Zhi-peng Li,1,2 Su-huan Liu,1 Xue-jun Li,1 Shu-yu Yang1

1Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, 2Department of Pharmacology, Beijing University of Chinese Medicine, Chao Yang District, Beijing, 3Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Abstract: 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.

Keywords: berberine, solid lipid nanoparticles, fatty liver, hepatosteatosis

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