Table I.

Role of RSV in different rheumatic diseases.

Disease	Disease mechanism	The therapeutic mechanism of RSV	Dose of RSV	Efficacy
T1DM	Islet resident DC uptake of beta cell antigens, presenting to naïve T cells and promoting Th1 differentiation will activate B lymphocytes that will produce autoantibodies against beta cells. Th1 will also activate macrophage and neutrophil migrations to the islet that will promote beta cell destruction by increasing ROS (19,66–69).	RSV acts via SIRT1 to inhibit apoptotic cell injury during oxidative stress and increases antioxidant capacity by reducing ROS. In addition, it plays a role in restoring beta cells in the islets (19,70).	Orally 250 mg/kg, orubcutaneous injection 25 mg/kg or 10 mg/kg intraperitoneally (71,72).	Reversing higher stages of insulitis in the islets of Langerhans. Decrement in glycosuria (71,72).
IBD	The activation of neutrophils and macrophages in the epithelium leads to the production of inflammatory mediators, such as ROS and TNF-α. Antigen recognition by naïve T lymphocytes induces the differentiation to Th1 and Th17 profiles in Crohn's disease, and to Th2 and Th17 profiles in ulcerative colitis, with the release of inflammatory cytokines, especially TNF-α (19,71–75).	RSV is capable of acting on the inhibition of inflammatory cytokines and neutralizing ROS (19).	Orally 20 mg/kg or 500 mg/day (74,75).	NF-κB activity, plasma levels of inflammatory factors and highly sensitive C-reactive protein were reduced (76,77).
PsO	The immune complex activates resident DC cells and then releases IL-23 to activate T lymphocytes, promoting differentiation into Th17. IL-16 promotes differentiation into Th1. These cells produce three major cytokines, IL-17, IL-22 and IFN, which promote the proliferation of keratinocytes (78–80).	Inhibiting the production of IL-17 and directly inhibiting the proliferation of keratinocytes (19).	Orally 400 mg/kg/day (81).	Reduces the thickness of the animal's skin (81).
RA	T cells secrete cytokines to activate B cells, and autoantibody production increases. Th17 response increased with the increase of the pro-inflammatory cytokine IL-17. In addition, TNF-α and IL-1 production increased, stimulating synovial cells. Synovial fibroblasts at the site of inflammation increased COX2/PGE2 and decreased SIRT1. Macrophages increase the recruitment of neutrophils at the site of inflammation through increased ROS production and activation of MPO and NF-κB (19,82–85).	RSV is able to act by reducing the production of autoantibodies, Th17 population, oxidative stress and NF-κB activation and reduces COX2 and PGE2 expression and activates SIRT1 (86–89).	Orally 20 mg/kg (91).	Inhibits levels of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-6, IL-1, MPO and IL-4. It also inhibited NF-κB activation. Reduce the production of autoantibodies (89,90).
ALS	TAR DNA-binding protein 43 accumulation in the motor neuron cytoplasm deregulates mitochondrial biogenesis and SOD1 function, increasing glutamate and free radicals in the cytosol. Microglia detect an abnormal cell and activate naïve T-cell differentiation in the Th1 pattern that releases cytokines (TNF-α, INF, IL-1, IL-2, IL-6, and IL-7) (91,92).	RSV acts by activating SIRT1 and regulates its substrate expression, increases the SOD1 useful life, reduces ROS, and acts in mitochondrial biogenesis as an antioxidant and antiapoptotic (93).	Orally high fat diet containing 4 g resveratrol per kg diet (93).	It can reduce motor neuron degeneration and delay muscle atrophy (19,93).
AIH	Dense lymphoplasmic inflammatory infiltration occurs in the portal vein bundle (94,95). Activation and clonal expansion of T cells lead to the release of autoantibodies and pro-inflammatory cytokines by B cells (96).	RSV against concanavalin-A-(ConA-) induced liver injury by significantly inhibiting IL-2, IL-6, TNF-α (97).	Orally 30 mg/kg (98).	Inflammatory cytokines and infiltration of macrophages, neutrophils and T cells in the mouse liver were significantly reduced, and ConA-mediated downregulation of SIRT1 in the liver was reversed (98).

AIH, autoimmune hepatitis; ALS, amyotrophic lateral sclerosis; RA, rheumatoid arthritis; PsO, psoriasis; IBD, inflammatory bowel disease; T1DM, type 1 diabetes; RSV, resveratrol; DC, dendritic cell; IL, interleukin; Th, T-helper; ROS, reactive oxygen species; SIRT1, sirtuin-1; TNF-α, tumor necrosis factor alpha; IL, interleukin; IFN, interferon; COX, cyclooxygenase-2; PGE2, prostaglandin E2; MPO, myeloperoxidase; NF-κB, nuclear factor κ light chain enhancer of activated B cells; SOD1, superoxide dismutase 1; ConA, concanavalin A.