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.
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From The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2021) · cites this paper as [79]
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- Authors
- Zhou, Y., Cao, S., Wang, Y., Xu, P., Yan, J., Bin, W., Qiu, F., & Kang, N.
- Affiliations
- Shenyang Pharmaceutical University (CN)
- Corresponding author
- Qiu, Feng
- Kang, Ning
- Venue
- Fitoterapia
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 92
- Pages
- 230-237
- ISSN
- 0367-326X (ISSN-L)
- OpenAlex
- W1976833660
- Cited by
- 81
- References
- 30
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 7 · 2020: 11 · 2019: 4 · 2018: 8 · 2017: 10 · 2016: 6 · 2015: 7 · 2014: 2
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Fitoterapia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
- Keywords
- berberine, LDL receptor, hypolipidemic effect, jatrorrhizine, columbamine, berberrubine, hepatic lipid accumulation, hepatoma cells, isoquinoline alkaloids, oral bioavailability
- MeSH terms
- Hypolipidemic Agents, Berberine, Berberine Alkaloids, Dose-Response Relationship, Drug, Carcinoma, Hepatocellular, Humans, Lipoproteins, LDL, Liver Neoplasms, Plant Extracts, Receptors, LDL, RNA, Messenger, Up-Regulation, Berberis, Coptis, Lipid Metabolism, Hep G2 Cells
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