Cited by 199Berberine and alkaloids researchDrug Transport and Resistance MechanismsGut microbiota and health

Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway

Open access
Sun, Runbin, Yang, Na, Kong, Bo, Cao, Bei, Feng, Dong, Yu, Xiaoyi, Ge, Chun, Huang, Jingqiu +14 more·2017·Molecular Pharmacology

Abstract

Previous studies suggest that the lipid-lowering effect of berberine (BBR) involves actions on the low-density lipoprotein receptor and the AMP-activated protein kinase signaling pathways. However, the implication of these mechanisms is unclear because of the low bioavailability of BBR. Because the main action site of BBR is the gut and intestinal farnesoid X receptor (FXR) plays a pivotal role in the regulation of lipid metabolism, we hypothesized that the effects of BBR on intestinal FXR signaling pathway might account for its pharmacological effectiveness. Using wild type (WT) and intestine-specific FXR knockout (FXR int-/-) mice, we found that BBR prevented the development of high-fat-diet-induced obesity and ameliorated triglyceride accumulation in livers of WT, but not FXR int-/- mice. BBR increased conjugated bile acids in serum and their excretion in feces. Furthermore, BBR inhibited bile salt hydrolase (BSH) activity in gut microbiota, and significantly increased the levels of tauro-conjugated bile acids, especially tauro-cholic acid(TCA), in the intestine. Both BBR and TCA treatment activated the intestinal FXR pathway and reduced the expression of fatty-acid translocase Cd36 in the liver. These results indicate that BBR may exert its lipid-lowering effect primarily in the gut by modulating the turnover of bile acids and subsequently the ileal FXR signaling pathway. In summary, we provide the first evidence to suggest a new mechanism of BBR action in the intestine that involves, sequentially, inhibiting BSH, elevating TCA, and activating FXR, which lead to the suppression of hepatic expression of Cd36 that results in reduced uptake of long-chain fatty acids in the liver.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1124/mol.116.106617

Cites

67 of 67 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Berberine enriches short-chain fatty-acid-producing bacteria, modulates bile-acid metabolism and remodels the microbiota in models of obesity and insulin resistance.

    “Berberine enriches short-chain fatty-acid-producing bacteria, modulates bile-acid metabolism and remodels the microbiota in models of obesity and insulin resistance [95,97,98,99,100,101]”

    From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [98]

    The section “BBR Modulated Bile Acid Composition and BSH Activity” (page unavailable) reports that berberine inhibited microbial bile salt hydrolase and increased tauro-conjugated bile acids, supporting the bile-acid claim. It cites prior work on changes in fecal bacterial proportions in high-fat-diet-fed mice, but does not itself establish microbiota remodeling in obesity and insulin-resistance models; no passage found reports enrichment of short-chain-fatty-acid-producing bacteria. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 68 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Sun, R., Yang, N., Kong, B., Cao, B., Feng, D., Yu, X., Ge, C., Huang, J., Shen, J., Wang, P., Feng, S., Fei, F., Guo, J., He, J., Aa, N., Chen, Q., Pan, Y., Schumacher, J. D., Yang, C. S., Guo, G. L., Aa, J., & Wang, G.
Affiliations
Rutgers, The State University of New Jersey (US)
Venue
Molecular Pharmacology
Publisher
Elsevier BV
Published
2017-02
Volume
91
Issue
2
Pages
110-122
ISSN
0026-895X (ISSN-L)
OpenAlex
W2559834790
Cited by
199
References
68
Citations by year
2026: 18 · 2025: 19 · 2024: 22 · 2023: 21 · 2022: 32 · 2021: 37 · 2020: 22 · 2019: 15 · 2018: 9 · 2017: 3
FWCI
7.28
Type
journal article
Language
en
Open access
Locations
  • Molecular Pharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM104037)
  • National Institute of Environmental Health Sciences (T32ES007148)
Topics
  • Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
berberine, hepatic lipid metabolism, bile acid metabolism, bile salt hydrolase, gut microbiota, taurocholate, CD36, fatty acid uptake, high-fat diet-induced obesity, triglyceride accumulation, hypolipidemic effect
MeSH terms
Gastrointestinal Microbiome, Receptor, Farnesoid X-Activated, Animals, Hypolipidemic Agents, Bacteria, Berberine, Bile Acids and Salts, Body Weight, Feces, Gene Expression Regulation, Intestinal Mucosa, Lithocholic Acid, Liver, Male, Mice, Inbred C57BL, Obesity, Taurocholic Acid, Triglycerides, Signal Transduction, Receptors, Cytoplasmic and Nuclear, CD36 Antigens, Lipid Metabolism, Diet, High-Fat

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review