Berberine-loaded solid lipid nanoparticles are concentrated in the liver and ameliorate hepatosteatosis in db/db mice.
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.
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China ; Department of Pharmacology, Beijing University of Chinese Medicine, Chao Yang District, Beijing, People's Republic of China.
Mei
M
Xue
Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
Liang
L
Zhang
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Ming-xing
MX
Yang
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Wei
W
Zhang
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China ; Department of Pharmacology, Beijing University of Chinese Medicine, Chao Yang District, Beijing, People's Republic of China.
Xiu-min
XM
Li
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Zhi-min
ZM
Ou
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China ; Department of Pharmacology, Beijing University of Chinese Medicine, Chao Yang District, Beijing, People's Republic of China.
Zhi-peng
ZP
Li
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Su-huan
SH
Liu
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Xue-jun
XJ
Li
Xiamen Diabetes Institute, the First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China.
Shu-yu
SY
Yang
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001599:Berberine / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009929:Organ Size / Q000187:drug effects; D013230:Stearoyl-CoA Desaturase / Q000737:chemistry / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D008055:Lipids; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D001599:Berberine; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
berberine; fatty liver; hepatosteatosis; solid lipid nanoparticles