Evidence map›Paper›PMID 27367504›Full record

ArticleInvestigative ophthalmology & visual science2016

Beneficial Effects of Berberine on Oxidized LDL-Induced Cytotoxicity to Human Retinal Müller Cells.

Dongxu Fu, Jeremy Y Yu, Anna R Connell, Shihe Yang, Michelle B Hookham, Rebecca McLeese, Timothy J Lyons

Open access · goldAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 48 citations in OpenAlex.

  1. Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026
    Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Role of Autophagy in Type 2 Diabetes Mellitus: The Metabolic Clash.Journal of cellular and molecular medicine · 2024
    Review
  7. Review
  8. Article
  9. Review
  10. Review
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  12. Article
  13. Review
  14. Article
  15. Review
  16. Effects of Modified Low-Density Lipoproteins and Fenofibrate on an Outer Blood-Retina Barrier Model: Implications for Diabetic Retinopathy.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2020
    Article
  17. Article
  18. Review
  19. Article
  20. The Roles of AMPK in Revascularization.Cardiology research and practice · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Dongxu FuCentre for Experimental Medicine School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
Jeremy Y YuCentre for Experimental Medicine School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
Anna R ConnellCentre for Experimental Medicine School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
Shihe YangSection of Endocrinology and Diabetes, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.
Michelle B HookhamCentre for Experimental Medicine School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
Rebecca McLeeseCentre for Experimental Medicine School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
Timothy J LyonsCentre for Experimental Medicine School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
Queen's University Belfast · GBUniversity of Oklahoma Health Sciences Center · US

Funding

THE ROLE OF COMPLEX 1 IN MITOCHONDRIAL DYSFUNCTION & FREE RADICAL PROD IN TYPE 1P20RR024215 · NCRR · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SHORT, KEVIN R. · 2007 to 2011
$11.7M
NCRR NIH HHS P20 RR024215
6 · The paper itself

Abstract

purposeLimited mechanistic understanding of diabetic retinopathy (DR) has hindered therapeutic advances. Berberine, an isoquinolone alkaloid, has shown favorable effects on glucose and lipid metabolism in animal and human studies, but effects on DR are unknown. We previously demonstrated intraretinal extravasation and modification of LDL in human diabetes, and toxicity of modified LDL to human retinal Müller cells. We now explore pathogenic effects of modified LDL on Müller cells, and the efficacy of berberine in mitigating this cytotoxicity.

methodsConfluent human Müller cells were exposed to in vitro-modified 'highly oxidized, glycated (HOG-) LDL versus native-LDL (N-LDL; 200 mg protein/L) for 6 or 24 hours, with/without pretreatment with berberine (5 μM, 1 hour) and/or the adenosine monophosphate (AMP)-activated protein kinase (AMPK) inhibitor, Compound C (5 μM, 1 hour). Using techniques including Western blots, reactive oxygen species (ROS) detection assay, and quantitative real-time PCR, the following outcomes were assessed: cell viability (CCK-8 assay), autophagy (LC3, Beclin-1, ATG-5), apoptosis (cleaved caspase 3, cleaved poly-ADP ribose polymerase), oxidative stress (ROS, nuclear factor erythroid 2-related factor 2, glutathione peroxidase 1, NADPH oxidase 4), angiogenesis (VEGF, pigment epithelium-derived factor), inflammation (inducible nitric oxide synthase, intercellular adhesion molecule 1, IL-6, IL-8, TNF-α), and glial cell activation (glial fibrillary acidic protein).

resultsNative-LDL had no effect on cultured human Müller cells, but HOG-LDL exhibited marked toxicity, significantly decreasing viability and inducing autophagy, apoptosis, oxidative stress, expression of angiogenic factors, inflammation, and glial cell activation. Berberine attenuated all the effects of HOG-LDL (all P < 0.05), and its effects were mitigated by AMPK inhibition (P < 0.05).

conclusionsBerberine inhibits modified LDL-induced Müller cell injury by activating the AMPK pathway, and merits further study as an agent for preventing and/or treating DR.

Indexed as

Analysis of VarianceAntioxidantsApoptosisAutophagyBerberineBiomarkersCells, CulturedCell SurvivalDiabetic RetinopathyEpendymoglial CellsEye ProteinsHumansInterleukin-6Interleukin-8Lipoproteins, LDLNerve Growth FactorsAntioxidantsBerberineBiomarkersEye ProteinsInterleukin-6Interleukin-8Lipoproteins, LDLNerve Growth FactorsNitric Oxide Synthase Type IINOS2 protein, humanoxidized low density lipoproteinPigment Epithelium-Derived FactorReactive Oxygen SpeciesSerpinsTumor Necrosis Factor-alpha

Identifiers

PMID27367504
PMCPMC4961062
OpenAlexW2474525937

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.