TABLE 3.
Effects and mechanism of Salvia miltiorrhiza and its active ingredients on osteoporosis.
| Ingredient | In vivo/In vitro | Model | Administration | Dose/Time | Treatment effect | Mechanism | Diseases | References |
|---|---|---|---|---|---|---|---|---|
| Tanshinol | In vitro | Rat primary osteoblasts | - | 1∼10 mg/L for 2 and 10 days | Promote ALP activity of rat cranial osteoblasts | - | OP | Cui et al. (2004) |
| Water extract of Salvia miltiorrhiza | In vivo; In vitro | Prednisone-induced osteoporosis in rats; rat primary cultured osteoblasts | Oral gavage | 5 g/kg/d for 12 weeks; 10∼20 g/L for 2, 10 days | Increase the number of bone trabeculae, the weight of backbone and the content of bone organic matter. Promote ALP activity of rat cranial osteoblasts | - | OP | Cui et al. (2004) |
| Tanshinol | In vivo | Dexamethasone-treated larval zebrafish | Medicated bath | 0.5∼5 μM for 3∼9 days | Reverse dexamethasone-induced inhibition of bone formation, decrease bone mass, downregulate expression of osteoblast-specific genes (Runx2, ALP, OCN, Sp7), and decrease ability to accumulate ROS production and antioxidants | - | OP | Luo et al. (2016) |
| Tanshinol | In vitro | BMSCs | - | 2 × 10−6 M for 3, 5, 7 and 24 days | Increase the activity of ALP and the expression of OCN. | Nitric oxide pathway | OP | Zhang et al. (2017b) |
| Salvianolic acid B | In vitro | BMSCs | - | 2.5 × 10−6 M for 3, 5, 7 and 24 days | Reverse the inhibitory effect of N-nitrol-arginine methyl ester on osteogenic differentiation of MSCs by reducing the expression of RANKL, and increase ALP, OCN and OPG/RANKL ratio | Nitric oxide pathway | OP | Zhang et al. (2017b) |
| Water extract of Salvia miltiorrhiza | In vivo; In vitro | OVX-induced osteoporosis rats; H2O2-induced preosteoblast cell | Oral gavage | 600 mg/kg/d for 12 weeks | Increase bone density and reduce bone separation | - | OP | Dong et al. (2018) |
| Salvianolic acid B | In vitro | Prednisone-induced osteoblasts | - | PA 48 h and Sal B 48 h | Enhancing the activity of osteoblasts and increasing the expression of Runx2, Osx, OCN, IGF-I, Col-I and HO-I genes related to bone formation and differentiation, prednisolone acetate treatment has a protective effect on osteoblasts | - | OP | Qiao et al. (2019) |
| Tanshinone ⅡA | In vitro | Dexamethasone -induced MC3T3-E1 | - | 0.001∼1,000 μM for 24 h | Reverse dex-induced apoptosis | Via inactivation of Nox4 | OP | Li et al. (2015) |
| Tanshinone ⅡA | In vivo | Growing rats | Oral gavage | 22 mg/kg/d for 1∼2 months | Significantly increase femoral bone mineral density, maximum femoral load and bone histomorphometric parameters in healthy female wistar rats, while serum OCN levels were increase and TRAP levels were decrease in the treated rats | - | OP | Yang et al. (2018) |
| Tanshinol | In vitro | C2C12; MC3T3-E1 | - | 0.0001∼1,000 μM | Alleviate microcirculation disorders and bone formation disorders reversed the accumulation of ROS, decrease cell viability, cell cycle arrest, and caspase 3-dependent apoptosis caused by oxidative stress | Downregulate FoxO3a signaling and upregulate Wnt signaling under oxidative stress | OP | Yang et al. (2013) |
| Tanshinone ⅡA | In vitro | Mouse bone marrow cells and calvarial osteoblasts | - | 0.5∼2.5 μg/mL for 7 days | Inhibit the osteoclast differentiation and reduce the formation of TRAP positive multinuclear osteoclasts | - | OP | Lee et al. (2005) |
| Tanshinone Ⅰ | In vitro | Mouse bone marrow cells and calvarial osteoblasts | - | 0.5∼2.5 μg/mL for 7 days | Inhibit the osteoclast differentiation and reduce the formation of TRAP positive multinuclear osteoclasts | - | OP | Lee et al. (2005) |
| Cryptotanshinone | In vitro | Mouse bone marrow cells and calvarial osteoblasts | - | 0.5∼2.5 μg/mL for 7 days | Inhibit the osteoclast differentiation and reduce the formation of TRAP positive multinuclear osteoclasts | - | OP | Lee et al. (2005) |
| Tanshinone ⅡA | In vitro | Osteoclasts | - | 10 μg/mL for 6, 12, 24, 48 h | Inhibit osteoclast differentiation | Inhibit c-Fos and NFATc1 expression. response to RANKL. | OP | Kwak et al. (2006) |
| Cryptotanshinone | In vitro | BMMs | - | 10∼80 μM for 5 days | Inhibit RANKL-induced the increase in TRAP activity in BMMs. In addition, the expressions of osteoclastogenesis-related marker proteins and NFAT activation were suppressed by cryptotanshinone treatment in BMMs | Inhibit ERK phosphorylation and NF-κB activation | OP | Wang et al. (2019b) |
| Protocatechuic aldehyde | In vitro | Raw 264.7; BMMs | - | 1, 10, 20, 30, and 50 μg/mL for 5∼6 days | Reduce osteoclast formation and bone resorption, and suppress the expression of mRNA encoded proteins associated with osteoclasts | Regulate NF-κB and MAPK pathways | OP | Qu et al. (2021) |
| Tanshinone | In vivo; In vitro | OVX-induced osteoporosis rats; BMSCs | Tail intravenous injection | 10 mg/kg/d for 2 weeks | Potently suppress OVX-induced osteoporosis and BMSC senescence | Through upregulation of PHGDH. | OP | Wang et al. (2019b) |
| Tanshinone ⅡA | In vitro | BMSCs | - | 1, 5 μM for 7 and 24 days | Promote osteogenesis and inhibit osteoclastogenesis | Upregulate BMP and Wnt signaling | OP | Qian et al. (2015) |
| Salvianolic acid B | In vivo; In vitro | prednisone-induced osteoblasts; BMSCs | Oral gavage | 40 and 80 mg/kg/d for 12 weeks; 10−6 mol/L∼10−7 mol/L for 14 days | Treat GC-induced bone loss in rats by stimulating osteogenesis, bone marrow angiogenesis and inhibiting lipogenesis | Dkk-1/β-catenin pathway | OP | Cui et al. (2012) |
| Tanshinol | In vivo; In vitro | prednisone-induced osteoporosis in rats; EA.hy926; MG63 | Oral gavage | 25 mg/kg/d for 14 weeks | Reduce microcirculation and bone formation disorders | Downregulate Wnt and VEGF pathways | OP | Lai et al. (2021) |
| Salvianolic acid B | In vivo; In vitro | rats spinal fusion model; EA hy9.26 | Surgical implantation | The concentrations of SB in the scaffolds were 0.26% (w/w, the mass ratio of PLGA to β-TCP to SB was 80:20:0.26), 1.3% and 2.60%, 8 weeks | Enhance bone fusion by promoting osteogenesis and angiogenesis | - | Spinal fusion | Lin et al. (2019) |
Note: OP, osteoporosis; ALP, alkaline phosphatase; Runx2, Runt-related transcription factor 2; OCN, ostecalcin; Osx/Sp7, Osterix; ROS, Reactive Oxygen Species; IGF-I, insulin-like growth factor 1; Col-I, type I collagen protein; HO-I, Heme Oxygenase-1; PA, Prednisolone acetate; Nox4, NADPH Oxidase 4; TRAP, tartrate resistant acid phosphatase; BMSCs, bone mesenchymal stem cells; RANKL, Receptor activator of nuclear factor kappa-B ligand; OPG, Osteoprotegerin; NFATc1, Nuclear Factor Of Activated T Cells 1; BMMs, bone marrow-derived macrophages; ERK, Extracellular regulated protein kinases; NF-κB, Nuclear factor kappa-B; MAPK, mitogen-activated protein kinase; OVX, Ovariectomy; PHGDH, phosphoglycerate dehydrogenase; BMP, bone morphogenetic protein; GC, Glucocorticoid; DKK-1, Dickkopf-related protein; VEGF, Vascular endothelial growth factor; PLGA, poly(lactic-co-glycolic acid); β-TCP, β-Tricalcium Phosphate.