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
Affiliations
Tapan Behl
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India
Tanuj Upadhyay
Amity Institute of Pharmacy, Amity University Gwalior, Gwalior 474005, Madhya Pradesh, India
Sukhbir Singh
Department of Pharmacology, Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India
Sridevi Chigurupati
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia
Amal M. Alsubayiel
Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia
Vasudevan Mani
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia
Celia Vargas-De-La-Cruz
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
Diana Uivarosan
Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
Cristiana Bustea
Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
Cristian Sava
Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
Manuela Stoicescu
Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
Andrei-Flavius Radu
Faculty of Medicine and Pharmacy, Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410073 Oradea, Romania
Simona Gabriela Bungau
Faculty of Medicine and Pharmacy, Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410073 Oradea, Romania
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.