TABLE 6.

Effects and mechanism of Salvia miltiorrhiza and its active ingredients on osteonecrosis of the femoral head.

Ingredient	In vivo/In vitro	Model	Administration	Dose/Time	Treatment effect	Mechanism	Diseases	References
Salvia miltiorrhiza injection	In vivo	Rabbit model of avascular necrotic femoral head	Injection	2 mL for 3 weeks and 6 weeks	Promote vascular recanalization by increasing the expression of VEGF and BMP-2 in femoral vein head	-	ONFH	Wu et al. (2019)
Salvianolic acid B	In vivo	Steroid-induced osteonecrosis of the femoral head in rats	Injection	40 mg/kg/d for 3 weeks	Increase the expression levels of Runx2 and Col-I	Inhibit the expression levels of PPARγ and AP2 proteins	ONFH	Li and Wang (2017)
TanshinoneⅠ	In vivo	Steroid-induced osteonecrosis of the femoral head rats	Intraperitoneal injection	5, 10 mg/kg/d for 4 weeks	Increase alkaline phosphatase activity and expressions of osteoblastic markers including OCN, Col-I, OPN, and Runx2 and decreased TRAP and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5	Activate the Nrf2 Signaling Pathway	SIONFH	Xu et al. (2021)

Note: ON-FH, osteonecrosis of the femoral head; SIONFH, steroid-induced femoral head necrosis; VEGF, Vascular endothelial growth factor; BMP-2, bone morphogenetic protein-2; Runx2, Runt-related transcription factor 2; Col-I, type I collagen protein; OCN, Ostecalcin; OPN, Osteopontin; TRAP, Tartrate resistant acid phosphatase; (PPAR)γ, peroxisome proliferator-activated receptor; AP2, Adipocyte protein 2.