TABLE 1.

The source, molecular structure, dose, cell lines and mechanism of 20 natural compounds on modulating osteoclat differentiation.

Compound name	Molecular structure	Source	Dose	In vitro studies cell lines	Mechanisms	Reference
Galangin		The rhizomes of Alpinia officinarum	0, 3, 6, 12 µM	BMMs	↓NF-κB and MAPKs signaling pathway;	Li et al. (2021a)
					↓(NFATc1, c-Jun and c-Fos)
Biochanin A		Trifolium pratense	0, 2, 4, 8, 16 µM	BMMs	↓NF-κB和/MAPKs signaling pathway;	Liao et al. (2021)
					↓(NFATc1, c-Fos ,IL-1αand IL-1β)
Vinpocetine		The alkaloid vincamine	0, 2.5, 5, 10, 20 µM	BMMs	↓NF-κB and MAPKs signaling pathway;	Zhu et al. (2020)
					↓(NFATc1, c-Fos ,TRAP and MMP-9)
Robinin		Vinca erecta Regel and Schmalh or Robinia pseudoacacia L	0, 0.25, 0.5, 1, 2,10, 20 µM	BMMs	↓NF-κB and MAPKs signaling pathway;	Hong et al. (2021)
					↓(Acp5, Cathepsin K, Atp6v0d2, Nfact1, c-Fos and Mmp9)
Urolithin B		One of gut microbial metabolites of ellagitannins	0, 10, 30, 50, 100 µM	RAW264.7 cells	↓NF-κB and MAPKs signaling pathway;	Qu et al. (2022)
					↓(c-Fos, NFATc1, Cathepsin K, TRAP, OC-STAMP and Mmp9)
Cinchonine		Cinchona bark	0, 10, 20, 30 µM	BMMs	↓AKT signaling pathway;	Jo et al. (2021)
					↓(NFATc1,AP-1, Dcstamp and Ctsk)
Cnidium lactone		Cnidium monnieri	10–6, 10–5, 10–4 mol/L	RAW264.7 cells	↓PI3K-Akt signaling pathway;	Liang et al. (2019), Wang et al. (2020)
					↓(p38,Acp5,CtsK, Atp6v0d2,Tm7sf4,Oscar and Nfatc1)
Anethole		Active agent of more than 20 plants	0, 1.25, 2.5, 7.25, 10 µM	BMMs	↓PI3K-Akt signaling pathway;	Qu et al. (2021)
					↓(TRAP, NFATc1, V-ATPase d2, c-Fos, MMP-9, CTR, DC-STAMP, cathepsin K,)
9,9′-O-di-(E)-fer-uloyl-meso-5,5′-55dimethoxysecoisolariciresinol		Litsea cubeba	0, 0.75, 1.5, 3, 15, 30 µM	BMMs	↓Akt signaling pathway ;	Yu et al. (2020)
					↓(NFATc1, c-Fos, MMP9)
Acacetin		Damiana, Saussurea involucrata plant, and black locust plants	0, 1, 5, 10, 20, 50,100 µM	BMMs	↓Akt/GSK3βsignaling pathway;	Lin et al. (2022)
					↓Ctsk, MMP9, , DC-STAMP, OSCAR, c-Fos, NFATc1 NFκB and Atp6v0d2)
Artesunate		Artemisinin	0, 1.56, 3.125, 6.25, 12.5 µM	RAW264.7 cells	↓PLCγ1-Ca2+-NFATc1 signaling pathway;	Zeng et al. (2020)
					↓(Fra-2,TRAP, Cathepsin K, β3-integrin, DC-STAMP, and Atp6v0d2)
Oleanolic acid acetate		Vigna angularis (azuki bean)	0, 5, 10, 20 µM	BMMs,	↓PLCγ1-Ca2+-NFATc1 signaling pathway;	Kim et al. (2014)
				BMCs	↓(TRAP and OSCAR)
Kirenol		Herba Siegesbeckiae	0, 1.25, 2.5, 5, 10 µM	BMMs	↓Ca2+-NFATc1 signaling pathway;	Zou et al. (2021)
					↓(NF-κB p65、 p-p38、p-ERK and c-Fos)
Asperpyrone A		Aspergillus niger	0, 0.5, 1, 2.5, 5, 10 µM	BMMs	↓Ca2+ oscillation;	Chen et al. (2019)
					↓(TRAP, NFATc1, c-Fos, Ctsk and Atp6v0d2)
Betulinic acid		The bark of the birch tree, D. kaki leaf and so on	0, 1, 5, 10 µM	BMMs	↓PLCγ1-Ca2+-NFATc1 signaling pathway;	Jeong et al. (2020)
					↓(TRAP, OSCAR, NFATc1, c-Fos, MMP9,β3-integrin, Ctsk, Mafb, Bcl6, Blimp1 and Atp6v0d2)
Loureirin B		Sanguis draxonis	0, 1, 2.5, 5, 10 µM	BMMs	↓ROS activity,MAPK-NFAT signaling pathway;	Liu et al. (2019)
					↓(Acp5, Atp6v0d2, Ctsk, MMP9 and c-Fos)
Schisandrin A		Schisandra chinensis	1, 50, 100, 200 µM	BMMs,	↓ROS activity;↑Nrf2 activity;	Ni et al. (2020)
				BMCs	↓(NFATc1,c-Fos,MMP9,TRAP)
Oroxylin A		The root of Scutellaria baicalensis Georgi	0, 1, 2.5, 5, 10 µM	BMMs	↓ROS activity;↑Nrf2 activity;	Xian et al. (2021)
					↓(c-Fos,NFATc1, Ctsk, Atp6v0d2)
Rhaponticin		Rheum undulatum L	0, 6.25, 12.5, 25, 50 µM	BMMs	↓ROS activity; ↑CAT, SOD-2 and HO-1 activity	He et al. (2021)
					↓(c-Fos,NFATc1, Ctsk, Atp6v0d2,Hprt)
Alpinetin		Alpinia Journal Pre-proof katsumadai Hayata	0, 5, 10, 15, 20, 30 µM	BMMs	↓ROS activity; ↑CAT, HO-1 and Nrf2 activity;	Wei et al. (2022)
					↓(c-Fos, Nfatc1, Ctsk, Tracp, Mmp9 and Dc-stamp)