ArticleCirculation2020
Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction.
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Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 76 citations in OpenAlex.
- New approach methodologies: drug screening platform to identify antifibrotic compounds.Nature protocols · 2026Review
- ML216 Alleviates Age-Related Cardiac Fibrosis by Suppressing TGF-β1 Signaling Pathway.International journal of molecular sciences · 2026Article
- Lycorine Attenuates Cardiac Fibrosis Through the Regulation of PYK2 Expression and Activity.Cardiovascular therapeutics · 2026Article
- 3D Cardiac Constructs in Drug Discovery: Current Advances and Future Challenges.Research (Washington, D.C.) · 2026Review
- Epicatechin inhibits inflammatory injury in preeclampsia extravillous trophoblasts.Reproduction (Cambridge, England) · 2025Article
- Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury.Chinese medicine · 2025Article
- miR-24-3p secreted as extracellular vesicle cargo by cardiomyocytes inhibits fibrosis in human cardiac microtissues.Cardiovascular research · 2025Article
- Gut commensal bacterium Bacteroides vulgatus exacerbates helminth-induced cardiac fibrosis through succinate accumulation.PLoS pathogens · 2025Article
- Dressed in Collagen: 2D and 3D Cardiac Fibrosis Models.International journal of molecular sciences · 2025Review
- Article
- Review
- Corynoline protects chronic pancreatitis via binding to PSMA2 and alleviating pancreatic fibrosis.Journal of gastroenterology · 2024Article
- Association of fibrotic markers with diastolic function after STEMI.Scientific reports · 2024Article
- Natural compound library screening to identify berberine as a treatment for rheumatoid arthritis.Clinical rheumatology · 2024Article
- Non-coding RNAs: targets for Chinese herbal medicine in treating myocardial fibrosis.Frontiers in pharmacology · 2024Review
- Musashi-2 causes cardiac hypertrophy and heart failure by inducing mitochondrial dysfunction through destabilizing Cluh and Smyd1 mRNA.Basic research in cardiology · 2023Article
- Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors.Journal of clinical and translational hepatology · 2023Review
- Akkermansia muciniphila participates in the host protection against helminth-induced cardiac fibrosis via TLR2.PLoS pathogens · 2023Article
- Zanubrutinib Ameliorates Cardiac Fibrosis and Inflammation Induced by Chronic Sympathetic Activation.Molecules (Basel, Switzerland) · 2023Article
- A Review of Therapeutic Strategies against Cardiac Fibrosis: From Classical Pharmacology to Novel Molecular, Epigenetic, and Biotechnological Approaches.Reviews in cardiovascular medicine · 2023Review
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Authors and funding
45 authors at 9 institutions in 4 countries.
Katharina SchimmelInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Mira JungInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Ariana FoinquinosInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Gorka San JoséProgram of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain (G.S.J., J.B., B.L., S.R., J.D., A.G.).
Javier BeaumontProgram of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain (G.S.J., J.B., B.L., S.R., J.D., A.G.).
Katharina BockInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Lea Grote-LeviInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Ke XiaoInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Christian BärInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Angelika PfanneInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Annette JustInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Karina ZimmerInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Soeun NgoyDepartment of Medicine, Divisions of Genetics and Cardiology (S.N., S.F., R.L.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Begoña LópezProgram of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain (G.S.J., J.B., B.L., S.R., J.D., A.G.).
Susana RavassaProgram of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain (G.S.J., J.B., B.L., S.R., J.D., A.G.).
Sabine SamolovacInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Heike Janssen-PetersInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Janet RemkeInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Kristian ScherfInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Seema DangwalInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Maria-Teresa PiccoliInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Felix KleemissInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Fabian Philipp KreutzerInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Franziska KennewegInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Julia LeonardyInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Lisa HobußInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Laura SanterInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Quoc-Tuan DoGreenpharma SAS, Department of Chemoinformatics, Orléans, France (Q.-T.D.).
Robert GeffersHelmholtz Centre for Infection Research, Research Group Genome Analytics, Braunschweig, Germany (R.G.).
Jan Hinrich BraesenInstitute for Pathology, Nephropathology Unit (J.H.B., J.S.), Hannover Medical School, Germany.
Jessica SchmitzInstitute for Pathology, Nephropathology Unit (J.H.B., J.S.), Hannover Medical School, Germany.
Christina BrandenbergerInstitute of Functional and Applied Anatomy (C. Brandenberger), Hannover Medical School, Germany.
Dominik N MüllerExperimental and Clinical Research Center, a cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Germany (D.N.M., N.W.).
Nicola WilckExperimental and Clinical Research Center, a cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Germany (D.N.M., N.W.).
Volkhard KaeverResearch Core Unit Metabolomics, Institute of Pharmacology (V.K., H.B.), Hannover Medical School, Germany.
Heike BähreResearch Core Unit Metabolomics, Institute of Pharmacology (V.K., H.B.), Hannover Medical School, Germany.
Sandor BatkaiInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Jan FiedlerInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Kevin M AlexanderCardiovascular Institute, Stanford University School of Medicine, CA (K.S., S.D., K.M.A., R.L.).
Bradley M WertheimDepartment of Medicine, Division of Pulmonary and Critical Care Medicine (B.M.W.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Sudeshna FischDepartment of Medicine, Divisions of Genetics and Cardiology (S.N., S.F., R.L.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Ronglih LiaoCardiovascular Institute, Stanford University School of Medicine, CA (K.S., S.D., K.M.A., R.L.).
Javier DiezProgram of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain (G.S.J., J.B., B.L., S.R., J.D., A.G.).
Arantxa GonzálezProgram of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain (G.S.J., J.B., B.L., S.R., J.D., A.G.).
Thomas ThumInstitute of Molecular and Translational Therapeutic Strategies (K.S., M.J., A.F., K.B., L.G.-L., K.X., C. Bär, A.P., A.J., K.Z., S.S., H.J.-P., J.R., K.S., S.D., M.-T.P., F.K., F.P.K., F.K., J.L., L.H., L.S., S.B., J.F., T.T.), Hannover Medical School, Germany.
Norwegian Womens Public Health Association · NOMedizinische Hochschule Hannover · DEInstituto de Salud Carlos III · ESBrigham and Women's Hospital · USCardiovascular Institute of the South · USMax Delbrück Center · DECheminPharma (United States) · USHelmholtz Centre for Infection Research · DEUniversidad Rey Juan Carlos · ES
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMyocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector cells of fibrosis in the heart. Therefore, our aim was to develop novel antifibrotic therapeutics based on naturally derived substance library screens for the treatment of cardiac fibrosis.
methodsAntifibrotic drug candidates were identified by functional screening of 480 chemically diverse natural compounds in primary human cardiac fibroblasts, subsequent validation, and mechanistic in vitro and in vivo studies. Hits were analyzed for dose-dependent inhibition of proliferation of human cardiac fibroblasts, modulation of apoptosis, and extracellular matrix expression. In vitro findings were confirmed in vivo with an angiotensin II-mediated murine model of cardiac fibrosis in both preventive and therapeutic settings, as well as in the Dahl salt-sensitive rat model. To investigate the mechanism underlying the antifibrotic potential of the lead compounds, treatment-dependent changes in the noncoding RNAome in primary human cardiac fibroblasts were analyzed by RNA deep sequencing.
resultsHigh-throughput natural compound library screening identified 15 substances with antiproliferative effects in human cardiac fibroblasts. Using multiple in vitro fibrosis assays and stringent selection algorithms, we identified the steroid bufalin (from Chinese toad venom) and the alkaloid lycorine (from
conclusionsWe identified the molecules bufalin and lycorine as drug candidates for therapeutic applications in cardiac fibrosis and diastolic dysfunction.
Indexed as
Amaryllidaceae AlkaloidsAnimalsApoptosisBufanolidesCardiomyopathiesCardiovascular AgentsCell ProliferationCells, CulturedDiastoleDisease Models, AnimalExtracellular MatrixFibroblastsFibrosisHigh-Throughput Screening AssaysHumansHypertensionAmaryllidaceae AlkaloidsbufalinBufanolidesCardiovascular AgentslycorineMicroRNAsMIRN671 microRNA, humanPhenanthridinesSELENOP protein, humanSelenoprotein PdiastolefibrosishypertensionmicroRNAs
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