Polyphenols Targeting MAPK Mediated Oxidative Stress and Inflammation in Rheumatoid Arthritis
Authors: Simona Gabriela Bungau
Tapan Behl
Vasudevan Mani
Cristiana Bustea
Tanuj Upadhyay
Manuela Stoicescu
Amal M Alsubayiel
Cristian Sava
Sridevi Chigurupati
Celia Vargas-De-La-Cruz
Andrei-Flavius Radu
Diana Uivarosan
Sukhbir Singh
Journal: Molecules (2021)
Discipline: CHEMISTRY
Keywords: TLR/MAPK; TNF; flavonoids; interleukin; oxidative
Affiliations: Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India., Amity Institute of Pharmacy, Amity University Gwalior, Gwalior 474005, Madhya Pradesh, India., Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia., Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia., Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia., Faculty of Pharmacy and Biochemistry, Academic Department of Pharmacology, Bromatology and Toxicology, Centro Latinoamericano de Enseñanza e Investigación en Bacteriología Alimentaria, Universidad Nacional Mayor de San Marcos, Lima 15001, Peru., Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania., Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania., Faculty of Medicine and Pharmacy, Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410073 Oradea, Romania.

Abstract:  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. 

Retracted: No

PubPeer comments:
 *Tortured phrases* are present in this paper: * **chain response** (*chain reaction*) * **redox flagging** (*redox signaling*) * **hyaluronic corrosive** (*hyaluronic acid*) and a few others. Could the authors please explain how this happened? ,