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Mol Biosyst. 2015 Feb;11(2):463-74. doi: 10.1039/c4mb00500g. Epub 2014 Nov 20.

A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine.

Author information

1
State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism and Pharmacokinetics, Jiangsu Key laboratory of drug design and optimization, China Pharmaceutical University, Nanjing 210009, China. jiyea@cpu.edu.cn.

Abstract

Clinical and animal studies demonstrated that orally administered berberine had a distinct lipid-lowering effect. However, pharmacokinetic studies showed that berberine was poorly absorbed into the body so the levels of berberine in the blood and target tissues were far below the effective concentrations revealed. To probe the underlying mechanism, the effect of berberine on the biological system was studied on a high-fat-diet-induced hamster hyperlipidemia model. Our results showed that intragastrically-administered berberine was poorly absorbed into circulation and most berberine accumulated in gut content. Although the bioavailability of intragastrically administered berberine was much lower than that of intraperitoneally administered berberine, it had a stronger lipid-lowing effect, indicating that the gastrointestinal tract is a potential target for the hypolipidemic effect of berberine. A metabolomic study on both serum and gut content showed that orally administered berberine significantly regulated molecules involved in lipid metabolism, and increased the generation of bile acids in the hyperlipidemic model. DNA analysis revealed that the orally administered berberine modulated the gut microbiota, and berberine showed a significant inhibition of the 7α-dehydroxylation conversion of cholic acid to deoxycholic acid, indicating a decreased elimination of bile acids in the gut. However, in model hamsters, elevated bile acids failed to downregulate the expression and function of CYP7A1 in a negative feedback loop. It was suggested that the hypocholesterolemic effect of orally administered berberine involves modulating the turnover of bile acids and the farnesoid X receptor signal pathway.

PMID:
25411028
PMCID:
PMC4302037
DOI:
10.1039/c4mb00500g
[Indexed for MEDLINE]
Free PMC Article

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