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Methylxanthine derivative, pentoxifylline attenuates inflammation via NF-κB and AP-1 pathway inhibition in murine

E H T Thulshan Jayathilaka1, Moon-Moo Kim1

  • 1Department of Cosmetics Engineering, and Graduate School of Applied Chemistry·Food Engineering, Dong-Eui University, Busan 47340, Republic of Korea.

Journal of Bioscience and Bioengineering
|February 17, 2026
PubMed

Insights

Pentoxifylline, a safe methylxanthine derivative, effectively reduces inflammation by inhibiting key inflammatory mediators and pathways. This study highlights its potential as a novel therapeutic for chronic inflammatory diseases.

Area of Science:

  • Pharmacology
  • Immunology
  • Cell Biology

Background:

  • Current anti-inflammatory therapies have limitations for chronic inflammation.
  • Safer alternatives are needed for managing chronic inflammatory conditions.

Purpose of the Study:

  • To investigate the anti-inflammatory effects of pentoxifylline, a methylxanthine derivative.
  • To evaluate the safety and efficacy of pentoxifylline in cellular models of inflammation.

Main Methods:

  • Cytotoxicity assessed using MTT assay on RAW 264.7 cells.
  • Anti-inflammatory effects evaluated via Griess assay, qRT-PCR, Western blot, gene reporter assays, and scratch assays.
  • Lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells were utilized.

Main Results:

  • Pentoxifylline demonstrated no cytotoxicity up to 20 μM.
  • Reduced nitric oxide (NO) production, inflammatory gene expression (Nos2, Tnfα, Il1β), and protein levels (iNOS, TNFα, IL1β, IL6).
  • Inhibited NF-κB and AP-1 transcriptional activity and NF-κB nuclear translocation, reducing macrophage migration.

Conclusions:

  • Pentoxifylline exhibits significant multi-target anti-inflammatory effects.
  • Demonstrates a safe therapeutic window and potential for treating inflammatory diseases.
  • Its ability to inhibit key inflammatory pathways and cell migration supports its therapeutic promise.
Keywords:
Anti-inflammatoryMethylxanthineNF-κBPentoxifyllineRAW 264.7

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