Anti-inflammatory efficacy of some potentially bioactive natural products against rheumatoid arthritis

Abstract

Abstract Arthritis is a distinguished inflammatory disease whose onset is mostly proportional with increasing age. Its prominent symptoms include joint pain, stiffness, and decreased range of motion of the affected joints, as well as redness, warmth, and swelling in the joint. Among several kinds of arthritis, rheumatoid arthritis is most fatal kind of inflammatory joint disease affecting people worldwide. Rheumatoid arthritis is a painful autoimmune disease that leads to synovial fibroblast hyperproliferation and massive infiltration of inflammatory immune cells, including CD4+ T\xa0cells and innate immune cells such as macrophages, into the joints. Various proinflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-10, and IL-18 promote autoimmunity, chronic inflammation, and tissue destruction. Major anti-inflammatory drugs (such as non-steroidal anti-inflammatory drugs and corticosteroids) suppress inflammation-induced pain by inhibiting the activation and production of various enzymes (such as cyclooxygenase [COX]-1 and COX-2), cytokines (such as TNF-α and IL-1β), and transcription factors (such as nuclear factor-κB [NF-κB], c-Jun N-terminal kinases, and p38 kinases). The negative impacts of such anti-inflammatory medications are adverse effects including Cushing habitus, hypertension, hyperglycemia, gastrointestinal ulceration, and bleeding. Alternatives to these drugs are traditional medicines and natural products, which via their ameliorative activity and minimal side effects offer great hope as promising therapeutic candidates. This further spurs the identification of potential bioactive compounds and their development into drugs to treat this inflammatory disease. Several polyphenolic compounds, terpenoids, and alkaloids are well-known to exhibit significant anti-inflammatory activity in\xa0vivo as well as in\xa0vitro. They induce the apoptosis of activated T\xa0cells and effector T\xa0cells and inhibit the expression of proinflammatory genes (IL-1β, IL-6, and TNF-α), chemokines (chemokine [C-C motif] ligand [CCL]-2/monocyte chemoattractant protein [MCP]-1, CCL-7/MCP-3), and enzymes (COX-1 and COX-2). They interfere with receptor activator of nuclear factor κ-B ligand–mediated osteoclast differentiation by downregulating mitogen-activated protein kinases and the NF-κB pathway and suppressing nuclear factor of activated T\xa0cells, cytoplasmic 1, tartrate-resistant acid phosphatase, and osteoclast-associated immunoglobulin-like receptor messenger RNA expression to prevent the progression of this disease. Some of them also hinder arthritic progression and improve the histology of affected joints by decreasing lipid peroxidation and increasing the level of antioxidants (such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase) as well as Heme oxygenase-1 expression levels.