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Establishing a Cell-Based High-Content Screening Assay for TCM Compounds with Anti-Renal Fibrosis Effects.

Xi-Ting Wang1, Xue-Jiao Sun1, Cheng Li1

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This study developed a high-content screening (HCS) method to find traditional Chinese medicine (TCM) compounds that fight renal fibrosis. Eight effective compounds were identified, offering new avenues for chronic kidney disease treatment.

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Area of Science:

  • Nephrology
  • Pharmacology
  • Drug Discovery

Background:

  • Renal fibrosis is a key factor in chronic kidney disease (CKD) progression, with limited treatment options beyond renal replacement therapy.
  • Traditional Chinese Medicine (TCM) offers a promising source for novel antifibrotic compounds.
  • Developing effective screening methods is crucial for identifying these compounds.

Purpose of the Study:

  • To establish a robust cell-based high-content screening (HCS) assay for identifying TCM compounds with antifibrotic properties.
  • To screen a library of 344 TCM molecules for potential anti-renal fibrosis activity.
  • To validate identified compounds and explore novel therapeutic agents for CKD.

Main Methods:

  • Optimized experimental parameters for a stable and reproducible NRK49F cell-based model.
  • Validated the HCS model using a known TGF-β1 receptor inhibitor (SB525334) and established TCM antifibrotics (curcumin, emodin).
  • Screened a library of 344 TCM compounds using the validated HCS assay and performed verification experiments on positive hits.

Main Results:

  • A high-content screening (HCS) model was successfully developed and validated for identifying anti-renal fibrosis compounds.
  • Out of 344 TCM molecules screened, 16 showed prospective inhibitory activity.
  • Eight compounds demonstrated significant anti-renal fibrosis effects, including six novel agents: Ligustrazine, Glycyrrhizic acid, Astragaloside iv, Hydroxysafflor Yellow A, Crocin, and Gypenosides.

Conclusions:

  • The developed HCS assay is a reliable and effective tool for discovering TCM compounds with anti-renal fibrosis activity.
  • This study identified several promising compounds, including novel agents, for the potential treatment of renal fibrosis and CKD.
  • The HCS approach can be broadly applied to identify lead compounds from TCM for various diseases.