TABLE 7.

Effects and mechanism of Salvia miltiorrhiza and its active ingredients on fracture healing.

Ingredient	In vivo/In vitro	Model	Administration	Dose/Time	Treatment effect	Mechanism	Diseases	References
Salvia miltiorrhiza injection	In vivo	Femoral fracture in C57BL mice	Oral gavage	0.5 mL/d for 14,16, 18, 22, 26, 34, 65 days	Accelerate calcium deposition	-	Delayed fracture union	Zhang (1984)
Salvianolic acid B	In vivo	Rats tibia fracture model	Intraperitoneal injection	40 mg/kg/d for 3 weeks	Increase ALP activity and the secretion of osteocalcin, and accelerate early fracture healing of the tibia in rats	-	Delayed fracture union	He and Shen (2014)
Tanshinol	In vivo	Prednisone-induced delayed fracture union mouse model	Local injection	5 mg/kg for 18 days	Accelerate callus mineralization rate and promote fracture callus formation and microstructure	-	Delayed fracture union	Liu et al. (2018)
Tanshinol	In vivo; In vitro	Nonunion rabbits; ATDC5	Loca injection	5 mg/kg for 4 weeks; 0.1∼20 μmlo/L for 24, 48 and 72 h	Stimulate bone formation in the nonunion defect rabbit model, increase the expression of P-HDAC3, collagen II, Runx2, VEGFA, and OPN in vivo; accelerate endochondral ossification turnover	HDAC3-mediated endochondral ossification	Nonunion Healing	Zhou et al. (2020)

Note: ALP, alkaline phosphatase; Runx2, Runt-related transcription factor 2; VEGFA, Vascular endothelial growth factor-A; OPN, Osteopontin; P-HDAC3, phosphorylated histone deacetylase; collagen II, Type 2 collagen.