title: Berberine metabolites could induce low density lipoprotein receptor up-regulation to exert lipid-lowering effects in human hepatoma cells.
abstract: Berberine (BBR) is an isoquinoline alkaloid isolated from several Chinese herbal medicines, such as Coptis chinensis, Berberis aristata, and Coptis japonica. It exhibits a lipid-lowering effect by up-regulating the hepatic low density lipoprotein receptor (LDLR) expression. However, the plasma concentration of BBR is very low after oral administration for the reason that BBR is poorly absorbed and rapidly metabolized. Therefore, it is hard to explain the pharmacological effects of BBR in vivo. Here, RT-PCR, Western blotting and Oil Red O staining were used to investigate the effects of four BBR metabolites on LDLR expression and lipid accumulation in human hepatoma Hep G2 cells. Our results suggested that BBR increased the LDLR mRNA and protein levels in a time- and dose-dependent manner. Four metabolites of BBR, jatrorrhizine, columbamine, berberrubine and demethyleneberberine, were found to be able to up-regulate LDLR mRNA and protein expression. Moreover, almost all the metabolites had potent effects on inhibiting cellular lipid accumulation. These results suggest that both BBR and its metabolites exhibit lipid-lowering effects by up-regulating LDLR expression, and BBR and its metabolites might be the in vivo active forms of BBR produced after oral administration. This study provides information to help us understand the mechanisms underlying the hypolipidemic effects of BBR in vivo.
authors: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China; Department of Neurology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou 221004, PR China.
authors: Yan
authors: Y
authors: Zhou
authors: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Shijie
authors: S
authors: Cao
authors: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Ying
authors: Y
authors: Wang
authors: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Peixiang
authors: P
authors: Xu
authors: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Jiankun
authors: J
authors: Yan
authors: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Wen
authors: W
authors: Bin
authors: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: fengqiu20070118@163.com.
authors: Feng
authors: F
authors: Qiu
authors: Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: kangndd@163.com.
authors: Ning
authors: N
authors: Kang
mesh_terms: D001599:Berberine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000378:metabolism / Q000494:pharmacology; D028142:Berberis / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D039323:Coptis / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D001600:Berberine Alkaloids; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D010936:Plant Extracts; D012333:RNA, Messenger; D011973:Receptors, LDL; C055785:jatrorrhizine; D001599:Berberine; C115958:berberrubine; C477155:demethyleneberberine; C055786:columbamine
keywords: Berberine; Human hepatoma cells; LDLR; Lipid accumulation; Metabolites