Table 2.

Herbal preparations, plant extracts, isolated compounds, and dietary antioxidants tested in animal models of rheumatoid arthritis.

Therapy	Source	Model	Effect	Reference
Huo-Luo-Xiao-Ling Dan (herbal formula)		AIA rat	↓ pannus formation, ↓ synovial mononuclear cell infiltration. ↓ bone and cartilage destruction. ↓ synovial levels of IL-18, IL-1β, MMP-2, and MMP-9.	[134]
Oldenlandia diffusa  (decoction)		CIA rat	Improves general health conditions. ↓ serum levels of IL-1β and TNF-α. ↓ redness, ↓ swelling, and ↓ hyperemia of ankle and toe joints.	[135]
Terminalia arjuna  (bark extract)		CIA rat	Antioxidant effect correlates positively with antiarthritic activity. ↓ hind paw swelling, ↓ neutrophil infiltration, ↓ articular elastase level. ↓ joint levels of nitrites and oxidized lipids. Attenuates the fall in reduced glutathione and superoxide dismutase levels. ↑ joint catalase activity.	[136]
Withania somnifera  (aqueous extract of root)		CIA rat	↓ systemic oxidative stress: ↓ lipid peroxidation levels, ↓ glutathione-S-transferase activity, ↑ glutathione content in plasma, ↑ ferric-reducing ability of plasma. ↓ arthritic index and ↓ production of C-reactive protein and antinuclear antibodies in an extent comparable to methotrexate.	[137]
Polyphenol-rich extract	Extra virgin olive oil	CIA mouse	↓ joint edema, ↓ cell migration, ↓ cartilage degradation, ↓ bone erosion. ↓ levels of proinflammatory cytokines and prostaglandin E2. ↓ expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1. ↓ translocation of NF-κB to the nucleus.	[138]
Apocynin	Commercial	ZIA mouse	Partially reverses the inflammation-induced inhibition of cartilage proteoglycan synthesis.	[139]
Coenzyme Q10	Commercial	AIA rat	Potentiates the methotrexate action to reduce hind paw volume and to lower the levels of IL-1α and oxidized lipids and proteins in plasma. Mitigates the inhibitory action of methotrexate in the phagocytic capacity, oxidative burst, and metabolic activity of peripheral blood neutrophils.	[140]
Eleutheroside E	Acanthopanax senticosus Radix eleutherococci	CIA mouse	Ameliorates arthritis severity. ↓ NF-κB activity, ↓ inflammatory cell infiltration, ↓ TNF-α and IL-6 production. ↓ pannus formation, ↓ cartilage damage, ↓ bone erosion.	[141]
Ferulic acid	Oldenlandia diffusa	CIA rat	Improves general health conditions. ↓ serum levels of IL-1β and TNF-α. ↓ redness, ↓ swelling, and ↓ hyperemia of ankle and toe joints.	[135]
Hesperidin	Commercial	CIA rat	Antiarthritic activity correlates positively with antioxidant effect. ↓ paw erythema and edema, ↓ cell infiltration. ↓ pannus formation, ↓ synovial hyperplasia, ↓ bone resorption. ↓ joint levels of neutrophil elastase, nitric oxide, and lipid peroxidation. Mitigates depletion of reduced glutathione, superoxide dismutase, and catalase.	[133, 142]
Platycodin D	Platycodi radix	CIA mice	Antiarthritic activity correlates positively with antioxidant effect. ↓ cytokine production by splenocytes. ↓ joint swelling and ↓ synovial infiltration of inflammatory cells. ↓ the levels of myeloperoxidase, oxidized lipids, IL-6, and TNF-α in the inflamed paw.	[143]
Quercetin	Commercial	AIA rat	Ameliorates clinical signs of the disease. ↓ production of inflammatory mediators and nitric oxide in macrophages.	[144]

AIA: adjuvant-induced arthritis; CIA: collagen-induced arthritis; IL: interleukin; MMP: matrix metalloproteinase; NF-κB: nuclear factor-κB; TNF-α: tumor necrosis factor-α; ZIA: zymosan-induced arthritis.