Introduction
Methodology
Immunopathology of rheumatoid arthritis
Cytokine | Producer cells | Target Cell and Effect | Role in Rheumatoid Arthritis | Reference |
---|---|---|---|---|
TNF-α | Monocytes/Macrophages. | Pro-inflammatory action. Differentiation and activation of osteoclasts. Neovascularization of the endothelium. Inhibition of regulatory T lymphocytes. | Systemic bone erosion | [24] |
IL-6 | Monocytes/Macrophages. | Macrophage activation and proliferation, with differentiation into osteoclasts. Multiplication and differentiation of T lymphocytes in the Th17 subtype. | Systemic inflammation | [25] |
IL-1α/b | Monocytes/Macrophages. | Osteoclast activation. T lymphocytes differentiation. Vasodilation. | Pro-inflammatory | [26] |
IL-17 A | Th17 lymphocytes/neutrophils | Cell proliferation. IL-6 production. Chondrocyte multiplication. Myeloid cells and neutrophil chemotaxis. Endothelial neovascularization. | Pro-inflammatory | |
IL-23 | Macrophages | Development, maintenance, and expansion of Th17 lymphocytes. Induction of IL-21/IL-22 cytokine production. | Th17 lymphocytes | [29] |
IL-21 | Th17 lymphocytes/Th2 cells/NK cells | B cell maturation. Development of plasma cells and production of antibodies. | Glycosylation of arthritogenic autoantibodies | [30] |
IL-12 | Macrophages | Differentiation of Th1 lymphocytes | Cell-mediated immune responses, Th17 cell plasticity | [31] |
Phytochemical compounds in the treatment of rheumatoid arthritis
Flavonoids
Compound | Chemical structure | Mechanism of action | Effect | References |
---|---|---|---|---|
Flavonoids | ||||
Quercetin | Decreased expression of IL-17 A, IL-21, and TNF-α. Decreased migration of Th17 lymphocytes. Increased expression of IL-10. | Decreased morning pain. Anti-inflammatory activity. | ||
Hesperidin | Decreased expression of TNF-α. Decreased osteoclastogenesis. | Anti-inflammatory activity. Decreased destruction of joint cartilage. | [39] | |
Baicalin Aglycone | ** | Decreased ROS and cyclooxygenase production. Decreased activation of the NFkB signaling pathway. | Anti-inflammatory and antioxidant activity. | [9] |
Gentakwanin Hydroxygenkwanin Luteolin Apigenin | ** | Decreased NO and ROS production. Decreased production of TNF-α, IL-6, INF-γ, and IL-2. | Anti-inflammatory, immunomodulatory, and antioxidant activity. | |
Icariin | Decrease in osteoclastogenesis markers. Decrease in Th17 lymphocyte population. | Decreased destruction of bones and cartilage. Anti-inflammatory activity. | [42] | |
Liquiritin | Decreased BCL-2/BAX rate. JNKI/P38 phosphorylation. | Anti-inflammatory activity. Angiogenic activity. | [43] | |
Oroxylin A | Decreased rates of IL-1β, IL-6, TNF-γ, and IL-17. | Anti-inflammatory activity | [44] | |
Kaempferol | Decreased invasion, proliferation, and invasion of fibroblast-like synoviocytes. Decreased production of TNF-α. | Anti-inflammatory activity. Reduction of cellular infiltrate. | ||
Alkaloids | ||||
Sinomenine | Regulation of IL-6, IL-12, INF-γ, TNF-α, IL-1β, and Il-10. | Anti-inflammatory activity. | ||
Nicotine | Decreased rates of rheumatoid factor, C-reactive protein, NO, and myeloperoxidase. Reduced levels of IL-1 and IL-17. | Anti-inflammatory activity | [49] | |
Naloxone | Not specified. | Decreased joint pressure. | [50] | |
Koumine | Immunomodulation. | Attenuating RA progression. | [51] | |
Berberine | Decreased production of IL-6 and IL-17. Increased production of IL-10 and TGF-β. | Reduces synovial hyperplasia. Anti-inflammatory activity. | [52] | |
Fangchinoline | Decreased production of TNF-α, IL-6, NO, uric acid, and cerulopasmin. Decreased proliferation of chondrocytes. | Anti-inflammatory activity. Reduction of cartilage degradation. | [53] | |
Oxymatrine | Decreased production of IL-6 and IL-8. Decreased migration and invasion of fibroblast-like synoviocytes. Activation of the NFkB signaling pathway. Decreased Th17 lymphocyte population. Increased regulatory T lymphocyte population. | Anti-inflammatory activity. | [54] | |
Ellipticine | Inhibition of fibroblast-like synoviocytes proliferation. Induction of apoptosis. | Anti-inflammatory and pro-apoptotic activity. | [55] | |
Saponins | ||||
Araloside A | Decreased proliferation of fibroblast-like synoviocytes. Induction of apoptosis. Decreased production of IL-6, IL-8, Prostaglandin E2, and NO. Activation of NFkB signaling pathway. | Anti-inflammatory and pro-apoptotic activity. | [10] | |
Asperosaponin VI | Inhibits osteoclastogenesis, by inducing the expression of several genes and markers that lead to osteoclast proliferation. | Decreased bone destruction. | [15] | |
Tubeimoside I | Decreased production of IL-1β, IL-6, IL-8, and TNF-α. Decreased expression of MMP9. Attenuation of fibroblast-like synoviocytes phenotypes. | Anti-inflammatory activity. | [16] | |
Pedunculoside | Decreased migration and activation of fibroblast-like synoviocytes. Decreased production of IL-1β, IL-6, IL-8, and TNF-α. Activation of p38 protein. | Anti-inflammatory and pro-apoptotic activity. | [56] | |
Medecassoside | Decreased migration and invasion of fibroblast-like synoviocytes. Decreased production of IL-1β. Activation of NFkB signaling pathway. | Anti-inflammatory and pro-apoptotic activity. | [57] | |
Hecogenin | Decreased migration and invasion of fibroblast-like synoviocytes. Induces apoptosis by increasing caspases 3, 8, and 9. | Anti-inflammatory and pro-apoptotic activity. | ||
Platycodin D | Decreased production of IL-6 and TNF-α. | Anti-inflammatory activity. |