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Amentoflavone Induces Ferroptosis to Alleviate Proliferation, Migration, Invasion and Inflammation in Rheumatoid

Yan Ma1, Hongjun Lin2, Yunman Li3

  • 1Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, 100020, Beijing, People's Republic of China.

Cell Biochemistry and Biophysics
|October 1, 2024
PubMed

Insights

Amentoflavone (AMF) inhibits rheumatoid arthritis progression by inducing ferroptosis in fibroblast-like synoviocytes. This polyphenol compound targets PIN1, reducing cell proliferation, migration, invasion, and inflammation, offering a potential new treatment for RA.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Rheumatoid arthritis (RA) is a systemic autoimmune disease impacting global health.
  • Fibroblast-like synoviocytes (FLS) are key drivers of RA pathogenesis.
  • Novel therapeutic strategies targeting RA-FLS are urgently needed.

Purpose of the Study:

  • To investigate the therapeutic potential of Amentoflavone (AMF) on RA-FLS.
  • To elucidate the mechanism by which AMF affects RA-FLS biological behaviors.
  • To determine AMF's role in regulating PIN1 and ferroptosis in RA.

Main Methods:

  • Human RA-FLS (MH7A) treated with AMF or PIN1-targeting siRNAs.
  • Assays for cell viability (CCK-8), proliferation (EDU), migration (wound healing), and invasion (Transwell).
  • ELISA for inflammatory factors, ferroptosis analysis (Fe2+, lipid ROS, protein levels), pull-down assay, and Western blotting.

Main Results:

  • AMF and PIN1 knockdown suppressed RA-FLS proliferation, migration, invasion, and inflammation.
  • AMF promoted lipid peroxidation and ferroptosis in RA-FLS.
  • AMF directly inhibited PIN1 expression; PIN1 overexpression reversed AMF's effects on ferroptosis.

Conclusions:

  • AMF inhibits RA-FLS proliferation, migration, invasion, and inflammation by inducing ferroptosis via PIN1 inhibition.
  • AMF demonstrates promise as a therapeutic agent for rheumatoid arthritis.
  • Targeting PIN1-mediated ferroptosis represents a potential strategy for RA treatment.
Keywords:
AmentoflavoneFerroptosisInflammationMigrationRheumatoid arthritis

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