Table 2 Phytochemicals used in the treatment of rheumatoid arthritis

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.

[6,7,8, 38]

 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.

[40, 41]

 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.

[45, 46]

Alkaloids

Sinomenine

Regulation of IL-6, IL-12, INF-γ, TNF-α, IL-1β, and Il-10.

Anti-inflammatory activity.

[13, 47, 48]

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.