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

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.

Recent developments in solid lipid nanoparticle and surface-modified solid lipid nanoparticle delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases

“…In addition, the same research group also found that the bioavailability of the berberine in the liver was 20 times higher than in blood, which led to a reduction in diabetes-associated complications such as lipolysis enhancement and lipogenesis inhibition. 52 These studies confirm that delivery of the bioactive compound to the systemic circulation in a highly active way can enhance not only specific activities but also improve the associated complications. The bioavailability of certain other compounds such as curcumin, resveratrol, or quercetin was effectively enhanced through SLN delivery systems, but their activity in a diabetic animal model remains limited.…”

The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches

“…Entrapping berberine into solid lipid nanoparticles (SLNs) or berberine-loaded SLNs were studied for effect on lipid metabolism in the liver in db/db mice [60]. The maximum drug concentration in the liver was 20-fold higher than that in the blood.…”

Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect

“…The instrument and parameter configurations referred to the literature. 24 Pharmacokinetic data were processed using PKSolver 2.0, a freely available add-in Excel program.…”