Table 2.
Roles and mechanisms of various major types of ginsenosides
| Saponin | Osteogenesis | Osteoclastogenesis | |||
|---|---|---|---|---|---|
| In vitro | In vivo | Cells, effect and mechanism | |||
| Cells | Effect and mechanism | Animal model | Effect and mechanism | ||
| 1. Ginsenoside Rb1 | hAPDSCs (ALP activity, calcium mineralization↑) | Dose-dependently promote the osteogenic activity of hADSCs (0.5–6.0 μmol/L) [53] | RAW264.7 cells (RANKL↓, TRAP staining and activity ↓); inhibit osteoclast differentiation [61] | ||
| rMSCs(ALP activity↑, Runx-2, OCN, OPN, ALP expression↑) | Dose-dependently promote the osteogenic activity of rMSCs (0.01–1 μmol/L) [62] | OVX rats (serum analysis, mechanical testing, Masson Goldner trichrome staining, bone histomorphometry analysis) | No obvious effect on OVX rats [62] | Raw264.7 cells (c-Fos and NFATc1↓); inhibit osteoclast differentiation through JNK, p38 MAPKs and the NF-κB pathways [74] | |
| 2. Ginsenoside Rb2 | MC3T3-E1 (ALP activity↑, calcium mineralization, mRNA expressions of ALP, Col-1, OCN and OPN↑) | Promote the differentiation of osteoblasts and resist oxidative damage caused by H2O2 [54] | OVX rats (ROS measurement, Van Gieson staining) | BMD↑, MDA↓, GSH↑, Rb2 may partially improve the microstructure and bone mass of trabecular OVX mice, prevent and treat osteoporosis [54] | MC3T3-E1(RANKL↓, IL-6↓) [48]; RAW264.7 cell, inhibit osteoclast differentiation through NF-κB-STAT3 signalling pathways↓ [75] |
| 3. Ginsenoside Rc | RAW264.7 cells (RANKL↓, TRAP staining and activity ↓ ) [61] | ||||
| 4. Ginsenoside Rd | MC3T3-E1 (ALP activity, calcium mineralization↑, BMP-2 secretion↑, ALP, OCN, Col-1, BMP-2 expression↑) | Promotes osteogenesis through the AMPK-BMP-2 -smad signalling pathway [63] | BMMs (TRAP activity↓) inhibit osteoclast differentiation but cytotoxic [76] | ||
| 5. Ginsenoside Re | MC3T3-E1 (ALP staining and activity, Runx-2, Col-1, OCN, OPN expression↑) | Promote osteoblast differentiation [64] | Zebrafish scales (Alizarin red S staining) | Promote mineralization of zebrafish scales [64] | RAW264.7 cells (RANKL↓, TRAP staining and activity ↓) [61] BMMs and zebrafish scales (TRAP staining and activity↓) inhibit osteoclast differentiation through ERK and RANKL-induced signalling pathway [76] |
| 6. Ginsenoside Rf | RAW264.7 cells (RANKL↓, TRAP staining and activity ↓) [61] | ||||
| 7. Ginsenoside Rg1 | BMSCs (ALP staining↑, calcification↑ BMP-2, Runx2, OCN, Col-1 and ALP expression↑) | Promote the osteogenesis through GR-dependent BMP/Smad signalling pathway [55] | Rat tibial fracture model (Micro-CT scanner HE, Safranin-O/Fast Green and immunohistochemical staining) | Promoted the transformation from the fibrous callus to osteogenic callus, increased bone strength and accelerated fracture healing [55] | RAW264.7 cells (RANKL↓, TRAP staining and activity ↓) [61] |
| hPDLSCs (ALP activity↑, Runx-2, Col-1, OCN, OPN expression ↑) | Enhance osteogenic differentiation [56] | ||||
| hDPCs (ALP activity↑ mineralized calcium nodules↑) | Enhance osteogenic differentiation [57] | ||||
| hDPSCs (BMP-2, FGF-2 secretion↑, DSPP, ALP, OCN, BPM-2 and FGF2 mRNA↑) | The Roche Nimblegen Whole Human Genome Expression profile microarray; seven statistically significant pathways, gene expressions of DSPP↑ and DMP1↑ [58] | ||||
| 8. Ginsenoside Rh1 | MC3T3-E1 (ALP activity↑, Runx-2, Col-1, OCN expression↑, mineralized calcium nodules↑, glutathione contents↑) | Promote osteogenic differentiation and inhibit AMA-enhanced ROS [59] | |||
| 9. Ginsenoside Rh2(S) | MC3T3-E1 (ALP staining, calcification↑ ALP, Runx2, OSX, OCN, OPN and Col-1 expression↑) | Stimulated the differentiation and the mineralization through PKD/p38 MAPK and PKD/AMPK signalling pathway [70, 71] | |||
| 10. C-K | MC3T3-E1 (ALP activity, Col-1 content, and mineralization ↑ ALP, Runx2 and Col-1 expression↑) | Inhibited H2O2-induced ROS NO production and inflammation; stimulated osteoblast differentiation [72] | |||
| MC3T3-E1 (ALP activity, ALP, Col-1, and Runx2 expression↑) | Induce osteogenic differentiation through WNT signalling pathway [73] | ||||
| 11. Rg5:Rk1 | MC3T3-E1ALP activity↑, calcification↑ BMP-2, Runx2 and Col-1 expression↑ | They speculated that osteogenesis-promoting effect is achieved through the BMP-2/Runx2 pathway [60] | |||
| 12. Ginseng water extract: 1.19% Rb1, 0.12% Rb2, 0.57% Rg1, 0.07% Rc, 0.64% Re, and 0.04% Rf | OVX (µ-CT, Bone histomorphometric analysis) | Ginseng can prevent bone loss and trabecular microstructure deterioration caused by OVX. Ginseng may be a good drug for the prevention and treatment of postmenopausal osteoporosis [61] | RAW264.7 cells (RANKL↓, TRAP staining and activity ↓) The ginseng water extract and the five ginsenosides except Rb2 can inhibit osteoclast differentiation [61] | ||
↑: up-regulation ↓: down-regulation