, Volume 41, Issue 5, pp 1974–1986 | Cite as

Novel Anti-arthritic Mechanisms of Polydatin in Complete Freund’s Adjuvant-Induced Arthritis in Rats: Involvement of IL-6, STAT-3, IL-17, and NF-кB

  • Kamel M. KamelEmail author
  • Amany M. Gad
  • Suzan M. Mansour
  • Marwa M. Safar
  • Hala M. Fawzy


Articular manifestations are the main hall mark for rheumatoid arthritis; inflammation and oxidative stress are involved in its pathogenesis. This study was designed to figure out the possible therapeutic potential of polydatin on experimentally induced arthritis in rats. Polydatin (POLY) was administered (200 mg/kg, p.o.) for 21 days to complete Freund’s adjuvant (CFA; 0.1 ml, s.c.)-induced arthritic rats. Meanwhile, methotrexate (MTX; 0.75 mg/kg, i.p.) was given as a reference standard disease-modifying anti-rheumatic drug (DMARD). Both POLY and MTX significantly attenuated articular damage associated with CFA-induced arthritis. This was manifested by reducing levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and matrix metalloproteinase-3 (MMP-3), paralleled with marked decrease in hind paw and ankle diameters. Moreover, POLY and MTX downregulated gene expressions of receptor activator of nuclear factor kappa-B ligand (RANKL) as well as signal transducer and activator of transcription-3 (STAT3) besides hampering immunohistochemical staining of vascular endothelial growth factor (VEGF) and nuclear factor kappa-B (NF-κB). Furthermore, substantial decline in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level associated with significant rise in reduced glutathione content (GSH) was observed. These findings provide an innovative therapeutic approach of POLY as a natural anti-arthritic drug through modulating IL-6/STAT-3/IL-17/NF-кB cascade.

Graphical Abstract


polydatin methotrexate cytokines synovitis pannus 


Compliance and Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.


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Authors and Affiliations

  1. 1.Pharmacology DepartmentNational Organization for Drug Control and ResearchGizaEgypt
  2. 2.Pharmacology & Toxicology Department, Faculty of PharmacyCairo UniversityCairoEgypt
  3. 3.Pharmacology, Toxicology & Biochemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical IndustriesFuture University in EgyptNew CairoEgypt
  4. 4.Pharmacology & Biochemistry Department, Faculty of PharmacyThe British University in EgyptEl Sherouk CityEgypt

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