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Troxerutin-Mediated Complement Pathway Inhibition is a Disease-Modifying Treatment for Inflammatory Arthritis.

Debasis Sahu1,2, Subasa Chandra Bishwal3, Md Zubbair Malik4

  • 1Product Development Cell, National Institute of Immunology, New Delhi, India.

Frontiers in Cell and Developmental Biology
|April 18, 2022
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Summary

Troxerutin (TXR) demonstrates significant antiarthritic effects in a rat model, reducing inflammation and disease scores. This study highlights TXR

Keywords:
adjuvant induced arthritisanti-inflammatoryantioxidantiTRAQproteomicstroxerutin

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Area of Science:

  • Pharmacology and Toxicology
  • Rheumatology
  • Proteomics

Background:

  • Troxerutin (TXR) is a known phytochemical with anti-inflammatory and hepatoprotective properties.
  • The antiarthritic potential of TXR has not been fully elucidated.
  • Adjuvant-induced arthritis (AIA) is a relevant model for studying inflammatory arthritis.

Purpose of the Study:

  • To investigate the antiarthritic effects of Troxerutin (TXR) in an adjuvant-induced arthritic (AIA) rat model.
  • To identify the underlying molecular mechanisms of TXR's action in arthritis using proteomics.
  • To establish an effective dosage and treatment duration for TXR in AIA rats.

Main Methods:

  • Adjuvant-induced arthritis (AIA) rat model was established.
  • Troxerutin (TXR) was administered orally at varying doses (50, 100, 200 mg/kg).
  • Isobaric tags for relative and absolute quantitative (iTRAQ) proteomics and Western blot analysis were used to identify deregulated proteins in joint homogenates.

Main Results:

  • TXR significantly reduced arthritis scores in a dose-dependent manner.
  • Proteomics identified 65 deregulated proteins in AIA rats, with key proteins validated by Western blot.
  • In silico analysis indicated perturbation of complement component 9 (C9) in AIA.

Conclusions:

  • Troxerutin (TXR) exhibits significant antiarthritic properties in the AIA rat model.
  • TXR's mechanism involves modulation of key proteins, including complement component 9 (C9).
  • A dosage of 200 mg/kg TXR for 15 days is effective, suggesting potential clinical utility.