Correction to: Flavonoid quercetin–methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis
Unfortunately, the last co-author name was incorrect and swapped in the original publication. The complete correct name should read as below. Natkunam Ketheesan The original article has been corrected.
Flavonoid quercetin-methotrexate combination inhibits inflammatory mediators and matrix metalloproteinase expression, providing protection to joints in collagen-induced arthritis
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial tissues in joints, leading to progressive destruction of cartilage and joints. The disease-modifying anti-rheumatic drugs currently in use have side-effects. Thus, there is an urgent need for safe anti-inflammatory therapies for RA. This study aimed to evaluate the therapeutic effect of the flavonoid quercetin on arthritis in mice immunized with type II collagen (CII). An arthritis model was established in C57/BL6 mice by intradermal administration of chicken CII mixed with Freund’s complete adjuvant. Quercetin (30 mg/kg orally) and methotrexate (0.75 mg intraperitoneally twice a week) were administered to investigate their protective effects against collagen-induced arthritis (CIA). Levels of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and the matrix metalloproteinases (MMP), 3, and 9 were detected to assess the anti-inflammatory effect of quercetin. The mRNA expression of MMP3, MMP9, CCL2, and TNF-α was also measured by quantitative real-time PCR. Quercetin significantly alleviated joint inflammation by reducing the levels of circulating cytokines and MMPs. There was a significant decrease in the expression of TNFα and MMP genes in the ankle joints of arthritic mice. A significant reduction in the levels of knee-joint inflammatory mediators were observed with combined quercetin and methotrexate treatment. Thus, quercetin has the potential to prevent joint inflammation and could be used as an adjunct therapy for RA patients who have an inadequate response to anti-rheumatic monotherapy.
Redox-sensitive transcription factors play a significant role in the development of rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease which is associated with significant morbidity. Redox sensitive transcription factors including NF-κB, HIF, AP-1, and Nrf2 are intimately involved in the pathogenesis of RA. The treatment of this disease is limited by the elusive nature of the pathogenesis of RA. NF-κB is crucial for the maturation of immune cells as well as production of TNFα and MMPs, which escalate RA. HIF is essential for activation of inflammatory cells, angiogenesis and pannus formation in RA. AP-1 regulates cytokine and MMP production as well as synovial hyperplasia which are key processes in RA. Nrf2 is involved with chondrogenesis, osteoblastogenesis, prostaglandin secretion and ROS production in RA. Targeting two or more of these transcription factors may result in increased efficacy than either therapy in isolation. This review will highlight the control specific mediators on these transcription factors, the subsequent effect of these transcription factors once activated, and then mesh this with the pathogenesis of RA. The elucidation of key transcription factor regulation in the pathogenesis of RA may highlight the novel therapy interventions which may prove to have a greater efficacy than those therapies currently available.
The therapeutic potential of plant flavonoids on rheumatoid arthritis
Rheumatoid arthritis (RA) is an autoimmune condition that mainly affects peripheral joints. Although immunosuppressive drugs and non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat this condition, these drugs have severe side effects. Flavonoids are the most abundant phenolic compounds which exhibit anti-oxidant, anti-inflammatory and immunomodulatory properties. Many bioactive flavonoids have powerful anti-inflammatory effects. However, a very few have reached clinical use. Dietary flavonoids have been reported to control joint inflammation and alleviate arthritis symptoms in both human RA and animal models of arthritis. There is little scientific evidence about their mechanism of actions in RA. We review the therapeutic effects of different groups of flavonoids belonging to the most common and abundant groups on RA. In particular, the probable mechanisms of major flavonoids on cells and chemical messengers involved in the inflammatory signaling components of RA are discussed in detail.
Therapeutic effect of quercetin in collagen-induced arthritis
Quercetin, a bioactive flavonoid with anti-inflammatory, immunosuppressive,and protective properties, is a potential agent for the treatment of rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is the most commonly used animal model for studying the pathogenesis of RA. This study analysed the therapeutic role of quercetin in collagen-induced arthritis in C57BL/6 mice. The animals were allocated into five groups that were subjected to the following treatments: negative (untreated) control, positive control (arthritis-induced), arthritis+methotrexate, arthritis+quercetin, and arthritis+methotrexate+quercetin. Assessments of weight, oedema, joint damage, and cytokine production were used to determine the therapeutic effect of quercetin. This study demonstrated for the first time the anti-inflammatory and protective effects of quercetin in vivo in CIA. The results also showed that the concurrent administration of quercetin and methotrexate did not offer greater protection than the administration of a single agent. The use of quercetin as a monotherapeutic agent resulted in the lowest degree of joint inflammation and the highest protection.The reduced severity of the disease in animals treated with quercetin was associated with decreased levels of TNF-α, IL-1 β, IL-17, and MCP-1. In conclusion, this study determined that quercetin, which was non-toxic, produced better results than methotrexate for the protection of joints from arthritic inflammation in mice. Quercetin may be an alternative treatment for RA because it modulates the main pathogenic pathways of RA.