ArticleSpringerPlus2016
Natural flavonoids silymarin and quercetin improve the brain distribution of co-administered P-gp substrate drugs.
Article in SpringerPlus, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 69 citations in OpenAlex.
- Silymarin Reverses Seizure-Precipitating Effects of Alcohol and Associated Psychiatric Comorbidities, and Neurotoxicity in Pentylenetetrazol Pre-Kindled Mice.Neurotoxicity research · 2026Article
- Article
- Plant Alkaloids as Promising Anticancer Compounds with Blood-Brain Barrier Penetration in the Treatment of Glioblastoma: In Vitro and In Vivo Models.Molecules (Basel, Switzerland) · 2025Review
- A Revolutionary Approach for Combating Efflux Transporter-mediated Resistant Epilepsy: Advanced Drug Delivery Systems.Current pharmaceutical design · 2025Review
- Plants, Pills, and the Brain: Exploring Phytochemicals and Neurological Medicines.International journal of plant, animal and environmental sciences · 2025Article
- In silico evaluation of berberine and silymarin against metabolic targets: a rationale for OMICS technology-based co-formulation.In silico pharmacology · 2025Article
- Natural Products as a Tool to Modulate the Activity and Expression of Multidrug Resistance Proteins of Intestinal Barrier.Journal of xenobiotics · 2023Review
- Evaluation of phytochemical, proximate, antioxidant, and anti-nutrient properties ofInternational journal of biochemistry and molecular biology · 2023Article
- Pharmaceutical prospects of Silymarin for the treatment of neurological patients: an updated insight.Frontiers in neuroscience · 2023Review
- Silibinin Suppresses Tumor Cell-Intrinsic Resistance to Nintedanib and Enhances Its Clinical Activity in Lung Cancer.Cancers · 2021Article
- Impacts of Drug Interactions on Pharmacokinetics and the Brain Transporters: A Recent Review of Natural Compound-Drug Interactions in Brain Disorders.International journal of molecular sciences · 2021Review
- Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug-Drug Interaction Studies.Clinical pharmacokinetics · 2020Review
- Quercetin Is a Flavonoid Breast Cancer Resistance Protein Inhibitor with an Impact on the Oral Pharmacokinetics of Sulfasalazine in Rats.Pharmaceutics · 2020Article
- Article
- Overcoming transporter-mediated multidrug resistance in cancer: failures and achievements of the last decades.Drug delivery and translational research · 2019Review
- Honokiol nanomicellar formulation produced increased oral bioavailability and anticancer effects in triple negative breast cancer (TNBC).Colloids and surfaces. B, Biointerfaces · 2017Article
- A systematic review of silymarin and silibinin mechanisms for attenuating cerebral ischemia-reperfusion injuries.Avicenna journal of phytomedicineReview
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P-glycoprotein (P-gp), a well known efflux transporter in the blood brain barrier inhibits the uptake of substrate drugs into brain. The main aim of this study is to evaluate the effect of natural product based P-gp inhibitors on brain penetration of various CNS drugs which are P-gp substrates. In this study, we have evaluated the inhibitory effects of natural bioflavonoids (quercetin and silymarin) on P-gp by using digoxin and quinidine as model P-gp model substrate drugs. In vitro inhibitory effects were evaluated in Caco-2 cell lines using digoxin as a model drug and in vivo P-gp inhibiting effect was evaluated in mice model using quinidine as model drug. The accumulation and bidirectional transport of digoxin in Caco-2 cells was determined in presence and absence of quercetin and silymarin. Elacridar was used as standard P-gp inhibitor and used to compare the inhibitory effects of test compounds. The apical to basolateral transport of digoxin was increased where as basolateral to apical transport of digoxin was decreased in concentration dependent manner in the presence of elacridar, quercetin and silymarin. After intravenous administration of P-gp inhibitors, brain levels of quinidine were estimated using LC-MS method. Increased brain uptake was observed with quercetin (2.5-fold) and silymarin (3.5-fold). Though the brain penetration potential of P-gp substrates was lower than that observed in elacridar, both quercetin and silymarin improved plasma quinidine levels. Caco-2 permeability studies and brain uptake indicate that both quercetin and silymarin can inhibit P-gp mediated efflux of drug into brain. Our results suggest that both silymarin and quercetin could potentially increase the brain distribution of co-administered drugs that are P-gp substrates.
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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.