ArticleJournal of experimental & clinical cancer research : CR2020
TFEB-NF-κB inflammatory signaling axis: a novel therapeutic pathway of Dihydrotanshinone I in doxorubicin-induced cardiotoxicity.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 108 citations in OpenAlex.
- Comparative extracellular and intracellular anti-Mycobacterium tuberculosis activity of three tanshinones from Salvia miltiorrhiza and oral cryptotanshinone efficacy in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- TFEB Antagonizes Cardiac Hypertrophy and Failure by Enhancing Lysosomal Capacity and Mitochondrial Function.Circulation research · 2026Article
- Doxorubicin promotes the production of inflammatory cytokines in tumor-associated macrophages through activating lactate dehydrogenase A.Cell death discovery · 2026Article
- Anthracycline-induced cardiorenal toxicity: from molecular mechanisms to clinical management.Frontiers in cardiovascular medicine · 2026Review
- Engineered endothelial cells targeting and dihydrotanshinone I loaded bacterial extracellular vesicles for atherosclerosis therapy.Bioengineering & translational medicine · 2025Article
- FAERS based disproportionality analysis and network pharmacology investigation of doxorubicin associated drug induced cardiotoxicity.Scientific reports · 2025Article
- Modulation of Macrophage Polarization by Traditional Chinese Medicine in HFpEF: A Review of Mechanisms and Therapeutic Potentials.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Dihydrotanshinone I Targets PGAM1 to Induce SYVN1-Mediated Ubiquitination and Suppress Glycolysis in Hepatocellular Carcinoma.Phytotherapy research : PTR · 2025Article
- Advances in pharmacological research on myocardial remodeling agents: A decade in review.Medicine · 2025Review
- A universal gene expression signature-based strategy for the high-throughput discovery of anti-inflammatory drugs.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Unveiling the Complexities: Exploring Mechanisms of Anthracyclineinduced Cardiotoxicity.Current cardiology reviews · 2025Review
- Cardioprotective effect ofActa biochimica et biophysica Sinica · 2024Article
- Neutrophil Biomarkers Can Predict Cardiotoxicity of Anthracyclines in Breast Cancer.International journal of molecular sciences · 2024Article
- Eupatilin attenuates doxorubicin-induced cardiotoxicity by activating the PI3K-AKT signaling pathway in mice.Molecular and cellular biochemistry · 2024Article
- DL-3-Heliyon · 2024Article
- Cardiovascular Toxicity of Antineoplastic Treatments in Hematological Diseases: Focus on Molecular Mechanisms to Improve Therapeutic Management.Journal of clinical medicine · 2024Review
- New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Review
- Role of macrophage polarization in heart failure and traditional Chinese medicine treatment.Frontiers in pharmacology · 2024Review
- Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke.Current neuropharmacology · 2024Article
- Danshen injection ameliorates unilateral ureteral obstruction-induced renal fibrosis by inhibiting ferroptosis via activating SIRT1/GPX4 pathway.Frontiers in pharmacology · 2024Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDoxorubicin is effective in a variety of solid and hematological malignancies. Unfortunately, clinical application of doxorubicin is limited due to a cumulative dose-dependent cardiotoxicity. Dihydrotanshinone I (DHT) is a natural product from Salvia miltiorrhiza Bunge with multiple anti-tumor activity and anti-inflammation effects. However, its anti-doxorubicin-induced cardiotoxicity (DIC) effect, either in vivo or in vitro, has not been elucidated yet. This study aims to explore the anti-inflammation effects of DHT against DIC, and to elucidate the potential regulatory mechanism.
methodsEffects of DHT on DIC were assessed in zebrafish, C57BL/6 mice and H9C2 cardiomyocytes. Echocardiography, histological examination, flow cytometry, immunochemistry and immunofluorescence were utilized to evaluate cardio-protective effects and anti-inflammation effects. mTOR agonist and lentivirus vector carrying GFP-TFEB were applied to explore the regulatory signaling pathway.
resultsDHT improved cardiac function via inhibiting the activation of M1 macrophages and the excessive release of pro-inflammatory cytokines both in vivo and in vitro. The activation and nuclear localization of NF-κB were suppressed by DHT, and the effect was abolished by mTOR agonist with concomitant reduced expression of nuclear TFEB. Furthermore, reduced expression of nuclear TFEB is accompanied by up-regulated phosphorylation of IKKα/β and NF-κB, while TFEB overexpression reversed these changes. Intriguingly, DHT could upregulate nuclear expression of TFEB and reduce expressions of p-IKKα/β and p-NF-κB.
conclusionsOur results demonstrated that DHT can be applied as a novel cardioprotective compound in the anti-inflammation management of DIC via mTOR-TFEB-NF-κB signaling pathway. The current study implicates TFEB-IKK-NF-κB signaling axis as a previously undescribed, druggable pathway for DIC.
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