Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis
Abstract
:1. Introduction
Target Tissues | Bone | Periodontal Tissue | Cartilage |
---|---|---|---|
Ginsenoside | Functions | ||
G-Rb1 | osteoblast activity ↑ | cartilage degradation ↓ | |
osteoclastogenesis ↓ | inflammatory process ↓ | ||
osteoclastic activity ↓ | antioxidant activity ↑ | ||
bone mineral density ↑ | |||
G-Rb2 | osteoblastic cell proliferation ↑ | ||
osteoblast activity ↑ | |||
osteoclastogenesis ↓ | |||
osteoclastic activity ↓ | |||
antioxidant activity ↑ | |||
G-Rb3 | osteoclastogenesis ↓ | cartilage degradation ↓ | |
osteoclastic activity ↓ | |||
matrix degradation ↓ | |||
inflammatory process ↓ | |||
gingivitis ↓ | |||
G-Rc | osteoblastic cell viability ↑ | cartilage degradation ↓ | |
osteoblast activity ↑ | |||
bone mineral density ↑ | |||
G-Rd | osteoblast activity ↑ | osteoclastogenesis ↓ | cartilage degradation ↓ |
osteoclastic activity ↓ | |||
matrix degradation ↓ | |||
inflammatory process ↓ | |||
antimicrobial process ↑ | |||
G-Re | osteoblast activity ↑ | periodontal ligament fibroblast activity ↑ | |
osteoclastogenesis ↓ | inflammatory process ↓ | ||
osteoclastic activity ↓ | |||
G-Rf | periodontal ligament fibroblast activity ↑ | cartilage degradation ↓ | |
inflammatory process ↓ | intestinal inflammatory process ↓ | ||
antioxidant activity ↑ | |||
G-Rg1 | osteogenic differentiation from BMSCs ↑ | periodontal ligament fibroblast proliferation ↑ | cartilage degradation ↓ |
adipogenic differentiation from BMSCs ↓ | periodontal ligament fibroblast activity ↑ | ||
inflammatory process ↓ | |||
pyroptotic process ↓ | |||
G-Rg2 | osteoclastogenesis ↓ | ||
osteoclastic activity ↓ | |||
G-Rg3 | osteoblast activity ↑ | cartilage degradation ↓ | |
osteoclastogenesis ↓ | |||
osteoclastic activity ↓ | |||
bone mineral density ↑ | |||
G-Rh1 | osteoblastic cell proliferation ↑ | ||
osteoblast activity ↑ | |||
antioxidant activity ↑ | |||
G-Rh2 | osteoblast activity ↑ | antimicrobial process ↑ | |
osteoclastogenesis ↓ | |||
osteoclastic activity ↓ | |||
bone mineral density ↑ | |||
G-Rk1 | inflammatory process ↓ | ||
CK | osteoblast activity ↑ | cartilage degradation ↓ | |
osteoclastogenesis ↓ | chondrocyte proliferation ↑ | ||
osteoclastic activity ↓ | chondrocyte differentiation ↑ | ||
matrix degradation ↓ | inflammatory process ↓ | ||
bone mineral density ↑ | pyroptotic process ↓ | ||
antioxidant activity ↑ | |||
NGR1 | osteoblastic viability ↑ | alveolar osteoblast activity ↑ | |
osteoblastic differentiation ↑ | |||
osteoblast activity ↑ | |||
osteoclastogenesis ↓ | |||
osteoclastic activity ↓ | |||
antioxidant activity ↑ | |||
PNS | osteoblast activity ↑ | joint destruction ↓ | |
osteoclastogenesis ↓ | inflammatory process ↓ | ||
osteoclastic activity ↓ | |||
bone mineral density ↑ | |||
Ginseng Extracts | osteoblast activity ↑ | periodontal ligament fibroblast proliferation ↑ | |
osteoclastogenesis ↓ | periodontal ligament fibroblast activity ↑ | ||
bone mineral density ↑ | osteoclastogenesis ↓ | ||
osteoclastic activity ↓ | |||
matrix degradation ↓ | |||
alveolar bone protection | |||
inflammatory process ↓ | |||
antimicrobial process ↑ |
2. Panax Ginseng and Ginsenoside
3. Effects of Ginsenoside on Osteoporosis
Active Compound/Extracts | Properties | In Vitro Model | Activity and Mechanism | In Vivo Model | Activity and Mechanism |
---|---|---|---|---|---|
G-Rb1 | osteogenic | isolated osteoblasts from DEX-OP rats | ↑ ALP activity ↑ Runx2, OCN, and OPN mRNA (0.0145 mg/mL) [8] | DEX-OP rats | ↑ BMD and BV/TV ↓ DEX-induced OP through the AHR/PRELP/NF-κB signaling ↑ AHR and PRELP proteins ↓ NF-κB p65 protein (IP 3 and 6 mg/kg/day) [8] |
anti-osteoclastogenic | RAW264.7 cells | ↓ osteoclast differentiation ↓ TNFα mRNA ↓ c-Fos, NFATc1 mRNA ↓ nucleus translocation and activation of NF-κB ↓ JNK and p38 phosphorylation (0.1, 1, and 10 μM) [9] | |||
G-Rb2 | osteogenic | MC3T3-E1 cells, H2O2-induced oxidative damage model | ↑ cell proliferation ↑ ALP mRNA ↑ calcium deposition ↑ ALP, COL-1, OCN, and OPN mRNA against oxidative damage induced by H2O2 ↓ RANKL and IL-6 (0.1, 1, and 10 μM) [12] | OVX-OP mice | ↓ blood MDA in OVX mice ↑ GSH activity in OVX mice ↑ BMD in OVX mice (IP 4.6 and 18.5 μmol/kg/day) [12] |
KD-OP mice | ↑ bone volume fraction ↑ serum BALP ↑ OCN ↓ TRAP, PPAR-γ, and CTSK (IP 18.5 μmol/kg/day) [33] | ||||
anti-osteoclastogenic | RAW264.7 cells | ↓ TRAP (+) MNC generation and TRAP mRNA ↑ OPG mRNA ↓ bone resorption ↓ NFATc1, c-Fos, OSCAR, CTSK mRNA ↓ NF-κB activation ↓ STAT3 activation (0.1, 1, and 10 μM) [34] | |||
antioxidant | MC3T3-E1, H2O2-induced oxidative damage model | ↓ H2O2-induced production of ROS ↑ ALP, COL-1, OCN, and OPN mRNA against oxidative damage induced by H2O2 (0.1,1,10 μM) [12] | |||
G-Rc | osteogenic | MC3T3-E1 cells | ↑ cell viability ↑ ALP staining ↑ calcium deposition ↑ β-catenin, p-GSK-3β, Runx2, ALP, and COL-1 mRNA (25, 50, 100, 200, 400, and 800 μM) [35] | OVX-OP mice | ↑ BMD ↑ trabecular bone number ↑ microstructure of trabecular bone ↑ Runx2, ALP, COL-1, BMP-2, OCN, mRNA, protein (gavage 25 and 50 mg/kg) [35] |
G-Rd | osteogenic | MC3T3-E1 cells | ↑ ALP, COL-1, OCN, OPN, and OSX mRNA ↑ BMP-2 mRNA ↑ calcium deposition ↑ AMPK ↑ Smad1/5 phosphorylation (10, 20, and 40 μM) [36] | ||
G-Re | osteogenic | MC3T3-E1 cells | ↑ ALP activity ↑ Runx2, ALP, COL-1, OCN, and mRNA ↑ calcium deposition (5, 10, 25, 50, and 100 μM) [37] | ||
anti-osteoclastogenic | BMMs | ↓ TRAP (+) MNCs generation ↓ TRAP activity ↓ NFATc1, c-Fos, and TRAP mRNA ↓ ERK phosphorylation (1, 2.5, 5, 10, 25, 50, and 100 μM) [38] | zebrafish model | more narrow distribution of TRAP staining ↓ TRAP and CTSK mRNA [38] | |
G-Rg1 | osteogenic | BMSCs | ↑ osteogenic differentiation of BMMSCs (5,10,20 μg/mL) [56] | ||
antioxidant | BMSCs | ↓ adipogenic differentiation by decreasing oxidative stress ↓ adipocyte distribution aging mice (5, 10, 20 μg/mL) [56] | |||
G-Rg2 | anti-osteoclastogenic | BMMs | ↓ osteoclast differentiation ↓ c-Fos and NFATc1 mRNA ↓ TRAP, Acp5, and Oscar mRNA ↓ p38, ERK, and JNK phosphorylation (1, 5, 10, 20, and 40 μM) [39] | ||
G-Rg3 | osteogenic | MC3T3-E1 cells | ↑ phosphorylated AMPK and autophagy ↑ Runx2, ALP, COL-1, OCN, and OPN mRNA ↑ calcium deposition ↓ mTOR signaling (10 and 20 μmol/L) [17] | OVX-OP mice | ↓ OVX-induced BW increases, BMD decreases, and histological changes in femur tissues ↑ Runx2, ALP, COL-1, OCN, and OPN ↓ TRAP ↑ autophagy and AMPK signaling ↓ mTOR signaling (IP 20 mg/kg) [17] |
MC3T3-E1 cells | ↑ ALP, COL-1 mRNA (10 and 100 μg/mL) [41] | ||||
Primary osteoblasts | ↑ ALP activity ↑ calcium deposition ↓ RANKL mRNA and protein ↑ OPG mRNA and protein (1, 5, 10, 20, and 100 μM) [42] | GC-OP | ↓ DEXA-induced BW increases and BMD decreases ↓ TRACP-5b activity ↓ CTx ↑ BMP-2, BMPR1A, and Runx2 mRNA (gavage 10 and 20 mg/kg) [42] | ||
anti-osteoclastogenic | RAW264.7 cells | ↓ pit formation ↓ TRAP (+) MNC generation ↓ RANK, TRAP, and CTSK mRNA ↓ p38, ERK, and JNK phosphorylation (0.01, 0.1, 1, 10, and 100 μM) [40] | |||
G-Rh1 | osteogenic | MC3T3-E1 cells | ↑ cell growth ↑ ALP activity and COL-1 protein ↑ calcium deposition ↑ BMP-2 and Runx2 mRNA (0.01, 0.05, 0.5, and 5 μg/mL) [43] | ||
antioxidant | AMA presented MC3T3-E1 cells | ↑ glutathione ↓ ROS production enhanced by AMA (0.01, 0.05, 0.5, and 5 μg/mL) [43] | |||
G-Rh2 | osteogenic | MC3T3-E1 cells | ↑ ALP, COL-1, OCN, and OSX mRNA ↑ calcium deposition ↑ AMPK phosphorylation ↑ p38 phosphorylation [44] | C57BL/6 mice | ↑ BMD (IP 3 mg/kg) [46] |
MC3T3-E1 cells | ↑ ALP, COL-1 OCN, OPN, and OSX mRNA ↑ calcium deposition ↑ PKD and AMPK phosphorylation [45] | ||||
anti-osteoclastogenic | BMMs | ↓ TRAP (+) MNC generation ↓ c-Fos, NFATc1, TRAP, and Oscar ↓ ERK phosphorylation ↓ NF-κB (5, 10, and 20 μM) [46] | |||
CK | osteogenic | MC3T3-E1 | ↑ ALP activity ↑ Runx2, ALP, COL-1, mRNA ↑ OPG mRNA ↑ Wnt10b, Wnt11, Lrp5, β-catenin (1, 2, 4, 8, and 16 μM) [47] | rat open femoral fracture model | ↑ fracture repair (local injection 500 μM) [48] |
OVX-OP mice | ↓ osteoclast number and surface area ↑ bone structure characteristics ↑ ALP, OCN, and OPN (IHC staining) ↓ MMP-9 and CTSK (IHC staining) (IP, 10 mg/kg) [13] | ||||
BMSCs | ↑ ALP, OCN, OPN, and OSX mRNA ↑ calcium deposition ↑ nuclear translocation of β-catenin, expression of Runx2 ↑ hUVEC formation (1 and 10 μM) [48] | ||||
anti-osteoclastogenic | RAW264.7 cells, BMMs | ↓ TRAP (+) MNC generation ↓ NF-κB phosphorylation ↓ bone resorption (1 and 10 μM) [13] | |||
antioxidant | RAW264.7 cells | ↓ ROS activity (1 and 10 μM) [13] | |||
NGR1 | osteogenic | hASCs | ↑ cell migration and osteogenic differentiation ↑ VEGF mRNA ↑ adhesion and spreading of hASCs on the bio-inert glass surface ↓ RANKL/OPG expression ratio (0.01, 0.05, 0.5, and 5 μg/mL) [49] | ||
MC3T3-E1 cells | ↑ ALP activity ↑ ALP, COL-1, and OCN mRNA ↑ calcium deposition (5, 50, 100, 200, and 1000 μg/mL) [51] | ||||
MC3T3-E1 cells | ↑ Runx2, ALP, and COL-1, OCN ↑ calcium deposition in OS injury model (10, 25, and 50 μM) [52] | ||||
anti-osteoclastogenic | Raw264.7 cells | ↓ p38, ERK1/2, JNK1/2, and NF-κB phosphorylation ↓ TRAP (+) MNC generation ↓ osteoclast bone resorption (5, 10, and 20 μM) [50] | mouse calvarial osteolysis model | ↓ mouse calvarial osteolysis (IP 10 and20 mg/kg) [50] | |
antioxidant | MC3T3-E1, H2O2-induced oxidative damage model | ↓ H2O2-induced osteoblast apoptosis ↑ osteoblast viability ↓ H2O2-induced mitochondrial ROS restored mitochondrial membrane potential and blocked JNK activated by H2O2 (10, 25, and 50 μM) [52] | |||
PNS | osteogenic | MC3T3-E1 cells | ↑ ALP activity and calcium deposition ↑ COL-1 and OCN mRNA (0.05 and 0.5 mg/mL) [53] | ||
BMSCs | ↑ ALP activity and calcium deposition ↑ ALP, Cbfa1, and bone sialoprotein mRNA ↑ p38 and ERK phosphorylation [54] | ||||
OVX-OP mice | ↑ restore bone mass ↑ CD31 and OCN ↓ serum NTX (P.O. 40 and 80 mg/kg) [55] | ||||
Ginseng extracts | osteogenic | MC3T3-E1 cells | ↓ caspase-3 and -9 mRNA ↑ Bcl2, IAPs, and XIAP mRNA ↑ Runx2, ALP, and BMP mRNA ↑ ALP activity ↑ AKT phosphorylation ↓ JNK phosphorylation (250, 500, and 1000 mg/mL) [57] | OVX-OP mice | Pg or Bo alone did not affect OVX-induced bone loss recovered bone weight (Pg:Bo) ↑ BMD (Pg:Bo = 3:1) ↓ OC formation (Pg:Bo = 3:1) ↓ blood glucose level (Pg:Bo = 3:1) (P.O. 500 mg/kg/day) [58] |
GC-OP mice | ↓ bone loss (P.O. 100 mg/kg/d or 500 mg/kg/d) [57] |
4. Effects of Ginsenosides on Periodontal Disease
Active Compound/Extracts | Properties | In Vitro Model | Activity and Mechanism | In Vivo Model | Activity and Mechanism |
---|---|---|---|---|---|
G-Rb3 | anti-osteoclastogenic | RAW264.7 cells and BMMs | ↓ TRAP (+) MNC generation ↓ NFATc1, MMP-9, CTSK, and ACP mRNA ↓ MMP-9 and CTSK proteins ↓ p38, ERK, and p65 NF-κB phosphorylation (50, 100, and 150 μM) [10] | P. gingivalis -LPS-induced periodontitis in rats | ↓ p-ERK in alveolar bone surface, blood vessels, odontoblasts, and gingival epithelia ↓ gingivitis ↓ alveolar bone resorption (gingival injection, 100 μM) [10] |
P. gingivalis -LPS-induced periodontitis in rats | ↓ alveolar bone resorption ↓ TRAP (+) MNC generation (gingival injection, 100 μM) [14] | ||||
anti-inflammatory/antimicrobial/anti-pyroptotic | P. gingivalis-LPS-stimulated hPDLCs | ↓ IL-1β, IL-6, and IL-8 mRNA ↓ p38 and p65 NF-κB, AKT phosphorylation (25, 50, and 100 μM) [14] | |||
G-Rd | anti-osteoclastogenic | RAW264.7 cells and BMMs | ↓ TRAP (+) MNC generation ↓ RANKL-induced ACP, NFATc1, and MMP-9 mRNA (50 and 100 μM) [72] | ligature-induced periodontitis in mouse | ↓ CEJ–ABC distances ↓ alveolar resorption (gingival injection 300 μM) [72] |
anti-inflammatory/antimicrobial/anti-pyroptotic | hGFs via LPS stimulation | ↓ LPS-stimulated IL-1β, IL-6, and CXCL8 mRNA ↓ LPS-stimulated IL-1β, IL-6, and IL-8 secretion (100 and 200 μM) [72] | ligature-induced periodontitis in mouse | ↓ bacteria colonies (gingival injection 300 μM) [72] | |
P. gingivalis | ↓ total biomass of bio films (100 and 200 μM) [72] | ||||
G-Re, Ra8, Rf | osteogenic | hPDLCs | ↑ calcium deposition ↑ Runx2, ALP, and OPN mRNA (40 μM) [67] | ||
anti-inflammatory/antimicrobial/anti-pyroptotic | P. gingivalis -LPS-stimulated hPDLCs | ↑ HO-1 protein via the nuclear translocation of Nrf2 ↑ The HO-1 protein is regulated by EGFR ↓ PGE2, NO, and IL-6, TNF-α secretion ↓ COX2 and NOS protein (5, 10, 20, and 40 μM) [67] | |||
G-Rg1 | osteogenic | hPDLCs | ↑ cell proliferation ↑ Runx2, ALP, COL-1, OCN, and OPN mRNA ↑ calcium deposition (10 μmol/L) [68] | ||
hDPSCs | ↑ cell proliferation ↑ DSPP, ALP, and OCN mRNA ↑ BMP-2 and FGF-2 protein (5 μmol/L) [70] | ||||
hDPSCs | ↑ cell proliferation ↑ ALP activity ↑ calcium deposition ↑ DSPP and DMP-1 mRNA (0.5, 2.5, 5, and 10 μmol/L) [18] | ||||
anti-inflammatory/antimicrobial/anti-pyroptotic | hPDLCs | ↑ cell viability ↓ pyroptosis ↓ lactate dehydrogenase, IL-1β, and IL-18 secretion ↓ aberrant mitochondrial fission and mtROS production ↑ ATP content and mitochondrial membrane potential level ↑ Drp1 phosphorylation ↓ NLRP3, ASC, Caspase-1, and GSDMD-NT mRNA (50, 100, and 200 μM) [69] | |||
G-Rh2 | anti-inflammatory/antimicrobial/anti-pyroptotic | Streptococcus mutans, Streptococcus sobrinus, and Streptococcus sanguinis | ↓ biomass accumulation ↓ bacterial growth ↓ extracellular polysaccharide synthesis disrupts cell membranes ↓ acetaldehyde/alcohol dehydrogenase mRNA (6.25, 12.5, 25, 50, and100 ng μL−1) [73] | ||
P. gingivalis | ↑ clearance of P. gingivalis [74] | ||||
NGR1 | osteogenic | hAOBs | ↑ ALP activity ↑ Runx2, OCN, and OPN ↓ p50 and p-p65 ↓ DKK1 mRNA ↑ AXIN2 and β-catenin mRNA ↑ calcium deposition (2.5, 5, 10, 20, and 40 μmol/L) [71] | ||
Ginseng extracts | osteogenic | hPDLCs | ↑ Runx2, ALP, COL-1, and OPN mRNA protein ↑ Calcium deposition (50, 100, 150, and 200 μg/mL) [78] | ligature-induced periodontitis in mouse P. gingivalis -LPS-induced periodontitis in rats | ligature-induced periodontitis in mouse ↑ alveolar bone volume after tooth extraction ↑ BMD of the tooth socket P. gingivalis-LPS-induced periodontitis in rats ↓ alveolar bone loss restored BMD loss ↓ inflammatory invasion of periodontal cells (gingival injection 50 mg/kg) [78] |
hPDLCs | ↑ cell proliferation (0.25 and 2 mg/mL) [79] | P. gingivalis -LPS-induced periodontitis in rats | ↓ alveolar bone loss ↓ MMP-9 around the gingival connective tissue (gingival injection 150, 300, and 360 mg/kg) [80] | ||
anti-osteoclastogenic | RAW264.7 cells | ↓ LPS-stimulated TRAP(+) MNC generation (0.08, 0.4, and 2 mg/mL) [79] | |||
anti-inflammatory/antimicrobial/anti-pyroptotic | P. gingivalis -LPS-stimulated hPDLCs | ↓ TNF-α, IL-1β, and IL-6 secretion ↓ PGE2 and NO secretion ↓ NOS and COX2 protein ↑ HO-1 protein (50, 100, 150, and 200 μg/mL) [78] | |||
hPDLCs, RAW264.7 cells | ↓ LPS-induced MMP-2 in PDLF ↓ LPS-stimulated activation of JNK and ERK in RAW264.7 cells ↓ LPS-stimulated degradation of IKB in RAW264.7 cells ↓ MMP-9 and iNOS in RAW264.7 cells ↓ NOS in RAW264.7 cells (0.08, 0.4, and 2 mg/mL) [79] | ||||
hGFs and hPDLCs | ↓ TNF-α and IL-6 secretion (0.156, 0.312, and 0.625 mg/mL) [80] | ||||
P. gingivalis | Symphytum officinale (S), Panax Ginseng (G), and metronidazole (F) S+F: biofilm inhibition (98.7%) G+F: biofilm inhibition (98.2%) [81] |
5. Effects of Ginsenosides on Osteoarthritis
Active Compound/Extracts | Chondroprotective | Anti-Inflammatory/Anti-Pyroptotic | ||
---|---|---|---|---|
Experimental Model | Activity and Mechanism | Experimental Model | Activity and Mechanism | |
G-Rb1 | chondrocytes with osteoarthritis | ↓ intracellular ROS production (30 and100 μg/kg) [11] | ||
hollow trephine on femur trochlea-induced rabbit OA | ↓ PGE2 and MMP-3 serum level ↑ TIMP-1 mRNA ↓ MMP-13-, MMP-3, and MMP-1 mRNA ↓ p-Akt, p-P65, and p-p38 protein ↓ chondrocyte-related irregularities (implant, 30 and 100 μg/kg) [11] | |||
MIA-induced OA | ↑ histological structure ↓ IL-1β, IL-6, and TNF-α in joint tissues ↓ miR-12-5p levels ↑ FGF-18 (gavage, 5 mg/kg) [15] | |||
MIA-induced OA in OVX rat | ↑ BMP-2 and COL-2A mRNA ↓ MMP-13, COX2, and TGF-β mRNA ↓ pathological changes in MIA-induced OA in OVX rats ↓ cartilage and GAG degradation (intraarticularly injection, 3 and 10 μg/kg) [87] | MIA-induced OA in OVX rats | ↓ IL-1β, IL-6, MCP-1/CCL-2, COX2, and PGE2 serum level (intra-articular injection, 3 and 10 μg/kg) [87] | |
G-Rb3 | S12 murine articular cartilage cell line | ↓ MMP-3 secretion (1, 10, and 100 μg/mL) [88] | ||
G-Rc | chondrocyte (IL-1β-treated SW1353) | ↓ MMP-13 secretion (5, 10, 15, and 20 μM) [89] | ||
G-Rd | S12 murine articular cartilage cell line | ↓ MMP-3 secretion (1,10,100 μg/mL) [88] | ||
chondrocyte (IL-1β-treated SW1353) | ↓ MMP-13 secretion (5, 10, 15, and 20 μM) [89] | |||
G-Rf | chondrocyte (IL-1β-treated SW1353) | ↓ MMP-13 secretion (5, 10, 15, and 20 μM) [89] | TNF-α-stimulated HT-29 cells, RAW264.7 cells | ↓ IL-1β, IL-6, TNF-α, NO, and ROS secretion ↓ TNF-α/LPS-induced NF-κB phosphorylation [90] |
G-Rg1 | IL-1β-induced chondrocyte | ↓ MMP-13, COX2, and PGE2 mRNA, protein ↓ COL-2 and aggrecan degradation (0.1, 1, and 10 μg/mL) [20] | ||
ACLT–OA rats | ↓ cartilage degeneration ↓ COL-2 loss and MMP-13 level (0.1, 1, and 10 μg/mL) [20] | |||
G-Rg3 | chondrocyte (IL-1β-treated SW1353) | ↓ MMP-13 secretion (5, 10, 15, and 20 μM) [89] | ||
G-Rk1 | LPS-stimulated RAW264.7 cells | ↓ NO, IL-6, IL-1β, TNF-α, and MCP-1 mRNA ↓ NF-κB and Jak2/STAT3 phosphorylation (10, 20, and 40 μmol/L) [91] | ||
CK | H2O2-stimulated MC3T3-E1 | ↑ ALP and COL-1 activity ↑ calcium deposition ↑ ALP and COL-1 mRNA [92] | H2O2-stimulated MC3T3-E1 cells | ↓ H2O2-induced ROS and NO ↓ IKK and IL-1β [92] |
PMCs | ↓ MMP-3 and MMP-13, ADAMTS5 secretion ↓ IL-6 secretion ↓ IL-1β protein (10, 20, and 50 μM) [93] | PMCs | ↓ NLRP3, GSDMD-NT, and caspase-1 protein (10, 20, and 50 μM) [93] | |
immature murine articular chondrocytes (iMACs) | ↑ chondrocyte proliferation ↑ chondrocyte differentiation ↓ cellular senescence and apoptosis-related gene expression [19] | |||
chondrocytes | ↓ MMP-3, MMP-13, ADAMTS4, and ADAMTS5 mRNA ↑ COL-2A mRNA ↓ IRE1α activation (0.3, 3, and 30 nM) [16] | chondrocytes | ↓ Caspase-1, GSDMD protein (0.3,3,30 nM) [16] | |
destabilization of the medial meniscus (DMM) of mice | ↓ OARSI score ↑ COL-2 ↓ MMP-13 (diet supplement, 40 mg/kg) [93] | destabilization of the medial meniscus (DMM) of mice | ↓ NLRP3 and GSDMD-NT protein 13 (diet supplement, 40 mg/kg) [93] | |
destabilization of the medial meniscus (DMM) of mice | ↑ aggrecan, COMP ↓ number of MMP-13-positive cells and TUNEL-positive cells ↓ number of pIkBα-positive cells ↓ AKT1, Annexin A2, and NFkB ↓apoptosis in osteoarthritic cartilage [19] | |||
MIA-induced rat OA | ↓ OARSI score ↓ MMP-13, IRE1α, and TXNIP level (gavage, 20 and 80 mg/kg/200 mL saline) [16] | MIA-induced rat OA | ↓ IL-1β, IL-18, and TNF-α serum levels ↓ caspase-1 activity and NLRP3 level (gavage, 20 and 80 mg/kg/200 mL saline) [16] | |
PNS | AIA rabbit | ↓ articular chondrocyte apoptosis ↓ lumbar vertebral and articular bone destruction ↓ arthritic muscular fiber atrophy ↓ inflammatory cell numbers ↑ bone density and microarchitecture (gavage, 75 mg/kg/day) [94] |
6. Conclusions
Funding
Conflicts of Interest
Abbreviations
References
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Ko, S.-Y. Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis. Int. J. Mol. Sci. 2024, 25, 5828. https://doi.org/10.3390/ijms25115828
Ko S-Y. Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis. International Journal of Molecular Sciences. 2024; 25(11):5828. https://doi.org/10.3390/ijms25115828
Chicago/Turabian StyleKo, Seon-Yle. 2024. "Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis" International Journal of Molecular Sciences 25, no. 11: 5828. https://doi.org/10.3390/ijms25115828