Table 3.

Effects and mechanisms of flavonoids on bone destruction in rheumatoid arthritis (RA).

Bioactivecompounds	Source	Chemical structure	Targets	Functions	References
Kaempferol	Kaempferia galanga L.		Down-regulated: MMP-1, MMP-3, COX-2, PGE2, ERK-1/2, p38, JNK, NF-κB, TRAP, CTR, MAPKs, c-Fos, NFATc1, CTSK, c-Jun Up-regulated: collagen I, Runx2, Osx, BMP-2, ATG5, beclin-1, LC3	inhibit osteoclast differentiation; promote osteoblast differentiation	(Yoon et al., 2013) (Lee et al., 2018) (Lee et al., 2014) (Kim et al., 2016)
Quercetin	Sophora japonica L.		Down-regulated: TNF-α, IL-1β, MCP-1, IL-17, ERK, IκBα, TRAP, CTSK, DC-STAMP, NFATc1, OC-STAMP, caspase3 Up-regulated: Wnt/β-catenin signaling pathway	inhibit osteoclast differentiation; promote osteoblast differentiation and inhibit osteoblast apoptosis	(Kim et al., 2019) (Guo C. et al., 2017)
Icariin	Epimedium brevicornu Maxim.		Down-regulated: TRAF6, ERK phosphorylation, NF-κB, MAPK signaling pathway	inhibit osteoclast formation and differentiation	(Kim B. et al., 2018) (Xu et al., 2019) (Hsieh et al., 2011)