ArticlePloS one2014
Mitochondria and NMDA receptor-dependent toxicity of berberine sensitizes neurons to glutamate and rotenone injury.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Anti-seizure Effects and Mechanisms of Berberine: A Systematic Review.Current pharmaceutical biotechnology · 2024Pooled it
- Unlocking the healing power of Berberine: A promising aid for multiple sclerosis.IBRO neuroscience reports · 2026Review
- A Fluorescence-Based Acetylcholinesterase Inhibition Assay for Bioactivity-Guided Identification of Neuroactive Protoberberine Alkaloids fromMolecules (Basel, Switzerland) · 2026Article
- Mitochondrial protective effects of ellagic acid in a rat model of sporadic Alzheimer's disease induced by STZ.Scientific reports · 2026Article
- Neuroprotective mechanisms of nutraceutical berberine: Preclinical evidence and future perspectives.Advances in neurotoxicology · 2026Article
- Ocular Toxicity and Mechanistic Investigation for Berberine and Its Metabolite Berberrubine on Zebrafish.Molecules (Basel, Switzerland) · 2025Article
- Polyphenols in the Central Nervous System: Cellular Effects and Liposomal Delivery Approaches.International journal of molecular sciences · 2025Review
- Natural Products in the Clinical Management of Metabolic Syndrome.Handbook of experimental pharmacology · 2025Review
- Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety.Expert opinion on drug metabolism & toxicology · 2024Review
- Review
- Berberine, a Herbal Metabolite in the Metabolic Syndrome: The Risk Factors, Course, and Consequences of the Disease.Molecules (Basel, Switzerland) · 2022Review
- Research progress on the pharmacological effects of berberine targeting mitochondria.Frontiers in endocrinology · 2022Review
- Apoptosis Induction, a Sharp Edge of Berberine to Exert Anti-Cancer Effects, Focus on Breast, Lung, and Liver Cancer.Frontiers in pharmacology · 2022Review
- Biological Activity of Berberine-A Summary Update.Toxins · 2020Review
- Caspase inhibition rescues F1Fo ATP synthase dysfunction-mediated dendritic spine elimination.Scientific reports · 2020Article
- Potential protective roles of phytochemicals on glutamate-induced neurotoxicity: A review.Iranian journal of basic medical sciences · 2020Review
- Article
- Article
- Excitatory pathway engaging glutamate, calcineurin, and NFAT upregulates IL-4 in ischemic neurons to polarize microglia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation.Molecular brain · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The global incidence of metabolic and age-related diseases, including type 2 diabetes and Alzheimer's disease, is on the rise. In addition to traditional pharmacotherapy, drug candidates from complementary and alternative medicine are actively being pursued for further drug development. Berberine, a nutraceutical traditionally used as an antibiotic, has recently been proposed to act as a multi-target protective agent against type 2 diabetes, dyslipidemias, ischemic brain injury and neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. However, the safety profile of berberine remains controversial, as isolated reports suggest risks with acute toxicity, bradycardia and exacerbation of neurodegeneration. We report that low micromolar berberine causes rapid mitochondria-dependent toxicity in primary neurons characterized by mitochondrial swelling, increased oxidative stress, decreased mitochondrial membrane potential and depletion of ATP content. Berberine does not induce caspase-3 activation and the resulting neurotoxicity remains unaffected by pan-caspase inhibitor treatment. Interestingly, inhibition of NMDA receptors by memantine and MK-801 completely blocked berberine-induced neurotoxicity. Additionally, subtoxic nanomolar concentrations of berberine were sufficient to sensitize neurons to glutamate excitotoxicity and rotenone injury. Our study highlights the need for further safety assessment of berberine, especially due to its tendency to accumulate in the CNS and the risk of potential neurotoxicity as a consequence of increasing bioavailability of berberine.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.