ArticlePloS one2014
Evaluation of the cardiotoxicity of mitragynine and its analogues using human induced pluripotent stem cell-derived cardiomyocytes.
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 34 papers, 1 of them a synthesis that pooled it.
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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.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Qualitative content analysis of public responses to an FDA inquiry on the impact of scheduling changes to kratom.The International journal on drug policy · 2022Pooled it
- Brugada Phenocopy Induced by Kratom Overdose.CJC open · 2026Article
- A Review of Kratom Product Evolution and Its Associated Health Outcomes.Substance abuse and rehabilitation · 2026Review
- Chronic kratom use as a precipitant for acquired Brugada syndrome.HeartRhythm case reports · 2025Article
- Kratom Cardiotoxicity: Reversible Brugada Pattern and QTc Prolongation.JACC. Case reports · 2025Article
- Exploring the Therapeutic Potential of Mitragynine and Corynoxeine: Kratom-Derived Indole and Oxindole Alkaloids for Pain Management.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Kratom: A Narrative Review of the Possible Clinical Uses and Dangers of This Opioid-Like Plant.Cureus · 2024Review
- Article
- Ventricular fibrillation during football training as a consequence of kratom and caffeine use in an adolescent: case report.European heart journal. Case reports · 2024Article
- A Critical Review of the Neuropharmacological Effects of Kratom: An Insight from the Functional Array of Identified Natural Compounds.Molecules (Basel, Switzerland) · 2023Review
- The potential of plant extracts in cell therapy.Stem cell research & therapy · 2022Review
- The Chemical and Pharmacological Properties of Mitragynine and Its Diastereomers: An Insight Review.Frontiers in pharmacology · 2022Review
- Understanding Kratom Use: A Guide for Healthcare Providers.Frontiers in pharmacology · 2022Review
- Psychoactive Substances of Natural Origin: Toxicological Aspects, Therapeutic Properties and Analysis in Biological Samples.Molecules (Basel, Switzerland) · 2021Review
- The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Frontiers in pharmacology · 2021Review
- Assessment of Cardiovascular Functioning Among Regular Kratom (Frontiers in pharmacology · 2021Article
- Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review.Pain and therapy · 2020Review
- Mitragynine, an euphoric compound inhibits hERG1a/1b channel current and upregulates the complexation of hERG1a-Hsp90 in HEK293-hERG1a/1b cells.Scientific reports · 2019Article
- Kratom policy: The challenge of balancing therapeutic potential with public safety.The International journal on drug policy · 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
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa), a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other chemical constituents isolated using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). METHODS AND
resultsThe rapid delayed rectifier potassium current (IKr), L-type Ca2+ current (ICa,L) and action potential duration (APD) were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM) was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM) suppressed IKr in hiPSC-CMs by 67%∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM) significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90) (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively) and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression, and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine.
conclusionsOur study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.
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