Polyphenols targeting MAPK mediated oxidative stress and inflammation in rheumatoid arthritis

Tapan Behl, Tanuj Upadhyay, Sukhbir Singh, Sridevi Chigurupati, Amal M. Alsubayiel, Vasudevan Mani, Celia Vargas-De-la-cruz, Diana Uivarosan, Cristiana Bustea, Cristian Sava, Manuela Stoicescu, Andrei Flavius Radu, Simona Gabriela Bungau

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder, predominantly symmetric, which causes joint inflammation, cartilage degeneration and bone erosion, resulting in deformity and the loss of physical function. Although the management of RA has steadily improved, the pathophysiological mechanism is incompletely elucidated, and therapeutic options are still limited. Due to shortcomings in the efficacy or safety profiles of conventional RA therapies, therapeutic alternatives have been considered. Therefore, natural extracts containing polyphenolic compounds can become promising adjuvant agents for RA global management, due to their antioxidant, anti-inflammatory and apoptotic properties. Polyphenols can regulate intracellular signaling pathways in RA and can generate different immune responses through some key factors (i.e., MAPK, interleukins (ILs 1 and 6), tumor necrosis factor (TNF), nuclear factor light k chain promoter of activated receptor (NF-κB), and c-Jun N-terminal kinases (JNK)). The critical function of the Toll like-receptor (TLR)-dependent mitogen-activating protein kinase (MAPK) signaling pathway in mediating the pathogenic characteristics of RA has been briefly discussed. Oxidative stress can trigger a change in transcription factors, which leads to the different expression of some genes involved in the inflammatory process. This review aims to provide a comprehensive perspective on the efficacy of polyphenols in mitigating RA by inhibiting signaling pathways, suggesting future research perspectives in order to validate their use.

Original languageEnglish
Article number6570
Issue number21
StatePublished - 1 Nov 2021
Externally publishedYes

Bibliographical note

Funding Information:
Funding: The publication of this paper was supported by the University of Oradea, Oradea, Romania through an internal project.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Flavonoids
  • Interleukin
  • Oxidative
  • Rheumatoid arthritis
  • Stilbenes
  • TNF


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