ArticleBritish journal of pharmacology2015
Protective effect of 23-hydroxybetulinic acid on doxorubicin-induced cardiotoxicity: a correlation with the inhibition of carbonyl reductase-mediated metabolism.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 38 citations in OpenAlex.
- 23-hydroxybetulinic acid induces cell cycle arrest in esophageal cancer cells via the BUB1/STAT3 signaling pathway.Frontiers in oncology · 2026Article
- Carbonyl reductase 1: a novel regulator of blood pressure in Down syndrome.Bioscience reports · 2025Article
- Thio-ProTide strategy: A novel HActa pharmaceutica Sinica. B · 2024Article
- Study on the Effect of Pharmaceutical Excipient PEG400 on the Pharmacokinetics of Baicalin in Cells Based on MRP2, MRP3, and BCRP Efflux Transporters.Pharmaceutics · 2024Article
- In vitro evaluation of the reductive carbonyl idarubicin metabolism to evaluate inhibitors of the formation of cardiotoxic idarubicinol via carbonyl and aldo-keto reductases.Archives of toxicology · 2024Article
- Is the combinational administration of doxorubicin and glutathione a reasonable proposal?Acta pharmacologica Sinica · 2019Article
- The Main Metabolites of Fluorouracil + Adriamycin + Cyclophosphamide (FAC) Are Not Major Contributors to FAC Toxicity in H9c2 Cardiac Differentiated Cells.Biomolecules · 2019Article
- Discovery of Novel Doxorubicin Metabolites in MCF7 Doxorubicin-Resistant Cells.Frontiers in pharmacology · 2019Article
- A Review of Resveratrol as a Potent Chemoprotective and Synergistic Agent in Cancer Chemotherapy.Frontiers in pharmacology · 2018Review
- Metabolic carbonyl reduction of anthracyclines - role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents.Investigational new drugs · 2017Review
- Drug target identification using network analysis: Taking active components in Sini decoction as an example.Scientific reports · 2016Article
- Cardioprotective Potentials of Plant-Derived Small Molecules against Doxorubicin Associated Cardiotoxicity.Oxidative medicine and cellular longevity · 2016Review
- Chinese innovation in cardiovascular drug discovery.British journal of pharmacology · 2015Article
- Role of Drug Metabolism in the Cytotoxicity and Clinical Efficacy of Anthracyclines.Current drug metabolism · 2015Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe clinical use of doxorubicin, an effective anticancer drug, is severely hampered by its cardiotoxicity. 23-Hydroxybetulinic acid (23-HBA), isolated from Pulsatilla chinensis, enhances the anticancer effect of doxorubicin while simultaneously reducing its cardiac toxicity, but does not affect the concentration of doxorubicin in the plasma and heart. As the metabolite doxorubicinol is more potent than doxorubicin at inducing cardiac toxicity, in the present study we aimed to clarify the role of doxorubicinol in the protective effect of 23-HBA. EXPERIMENTAL APPROACH: Doxorubicin was administered to mice for two weeks in the presence or absence of 23-HBA. The heart pathology, function, myocardial enzymes and accumulation of doxorubicin and doxorubicinol were then analysed. A cellular pharmacokinetic study of doxorubicin and doxorubicinol, carbonyl reductase 1 (CBR1) interference and molecular docking was performed in vitro. KEY
results23-HBA alleviated the doxorubicin-induced cardiotoxicity in mice, and this was accompanied by inhibition of the metabolism of doxorubicin and reduced accumulation of doxorubicinol selectively in hearts. In H9c2 cells, the protective effect of 23-HBA was shown to be closely associated with a decreased rate and extent of accumulation of doxorubicinol in mitochondria and nuclei. siRNA and docking analysis demonstrated that CBR1 has a crucial role in doxorubicin-mediated cardiotoxicity and 23-HBA inhibits this metabolic pathway. CONCLUSIONS AND IMPLICATIONS: Inhibition of CBR-mediated doxorubicin metabolism might be one of the protective mechanisms of 23-HBA against doxorubicin-induced cardiotoxicity. The present study provides a new research strategy guided by pharmacokinetic theory to elucidate the mechanism of drugs with unknown targets.
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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.