Table 4 The effect of NCs on MSCs differentiation in inflammatory environment
Natural product | Disease/back ground | MSC source | Effect | Results | Related mechanism /signaling pathway | References |
|---|---|---|---|---|---|---|
Astragalus | ||||||
Astragaloside IV 20–200 µM 40 mg/kg | Iron loading | Bone marrow | Osteogenic differentiation↑ Adipogenic differentiation↓ | Reduced adipogenesis and increased the osteogenic-related proteins (OCT4, SOX2, OCN, ALP) Reduced bone loss in mice | Iron homeostasis and metabolism | [46] |
Salvia miltiorrhiza Bunge | ||||||
SAC 5Â mM | LPS | Periodontal ligament | Osteogenic differentiation | Enhanced ALP activity and the ability of mineralization, osteogenic-related proteins (BMP-2, OCT4, SOX2, RUNX2) | N/A | [33] |
Ginsenoside | ||||||
Rb1 10−8 M/10−6 M 3 or 6 mg/kg | OVX osteoporosis | Bone marrow | Osteogenic differentiation | Increased ALP activity, mineralization, and the expression of osteogenic-related proteins in normal BMSCs in vitro; but did not have an effect on bone loss, dyslipidemia, and excessive oxidative stress in OVX osteoporosis rats | N/A | [23] |
Wedelolactone | ||||||
2 μg/mL | TNF-α | Dental pulp | Osteogenic differentiation | Promoted the nuclear accumulation of β-catenin, stimulated the expression of odontoblast-related marker genes (Dmp1, DSPP, Runx2) | Sema3A/NRP1/β-catenin↑ TNF-α/NF-κB↓ | [49] |
Osthole | ||||||
50–100 μM | Alcohol/alcohol-induced ONFH | Bone marrow | Osteogenic differentiation↑ adipogenic differentiation↓ | Rescued ALP activity and the expression of osteogenic genes (Col-I, Ocn and Opn) and proteins (RUNX2, COL-I, OCN) Decreased the expression of pivotal adipokines (Leptin and PPARγ) | Wnt/β-catenin ↑ | [48] |
10–7 M | Periodontitis | Periodontal ligament | Osteogenic differentiation | Reversed the expression of osteogenic-related genes and proteins (ALP, RUNX2, OSX), increased ALP staining and mineralization | MOZ & MORF ↑ Histone acetylation (H3K9 &H3K14) | [60] |
Berberine | ||||||
1–10 μM | LPS | Bone marrow | Osteogenic differentiation↑ Adipogenic differentiation↓ | Reverses the LPS-induced decrease in osteogenic gene expression and increase in adipogenic gene expression levels | AMPK ↑ | [31] |
EGCG | ||||||
0.52 μg/kg | Bone fracture | Tibial fracture mice | Osteogenic differentiation | Enhanced callus formation, increased bone volume, and subsequently improved the mechanical properties of the tibial bone | BMP-2 ↑ | [63] |
5–40 μM | Hypoxia | Bone marrow | Osteogenic differentiation | Upregulated the hypoxia-suppressed expression of RUNX2, BMP-2, ALP, and PINP | miR-210 ↑ | [62] |
Resveratrol | ||||||
200 μM | TNF-α | Bone marrow | Osteogenic differentiation↑ Adipogenic differentiation↓ | Upregulated ALP and Alizarin Red accumulation and osteoblast-related factors expression (COL-I, RUNX2) Downregulated Oil Red O accumulation and lipid drops | Hippo ↓ YAP/RUNX2 ↑ | [29] |
25 μM | Osteolysis induced by titanium | Bone marrow | Osteogenic differentiation | Promoted osteogenic differentiation and enhanced bone microstructure around the prosthesis. Enhanced the osteogenic genes (β-catenin, Runx2, Ocn) | Wnt/β-catenin ↑ | [54] |
15 μg/cm2 | Sterile inflammation with titanium implants | Bone marrow | Osteogenic differentiation | Enhanced the expression of osteogenesis-related genes (Ocn, Runx2, Opn, and Col-I), ALP activity and calcium deposition | NF-κB ↓ | [30] |
5 μM | TNF-β | Adipose tissue | Osteogenic differentiation | Reversed TNF-β-promoted impairments in MSCs osteogenesis | TNF-β/ NF-κB ↓ SIRT 1/Runx2↑ | [56] |
1 μM | Amyotrophic lateral sclerosis | Bone marrow | Neuronal differentiation | Increased neuroprogenitor markers expression (nestin, Musashi, CD133, GFAP) and promoted the neurite numbers and lengths | SIRT 1/AMPK↑ | [39] |
10 nM | TNF-α Periodontitis | Periodontal ligament | Osteogenic differentiation | Preserved the aggregate formation ability and osteogenesis | NFκB ↓ AMPK ↑ | [55] |
5 µM | TNF-α | Dental pulp | Osteogenic differentiation | Upregulated the expression of RUNX2, BMP-2, COL-I, and enhanced ALP staining in condition of 10 ng/ml TNF-α | SIRT1-Wnt/β-catenin ↑ | [53] |
< 50 µM | IL-1β | Bone marrow | Chondrogenic differentiation | Maintained chondrocyte markers (Col2, aggrecan and Sox9) mRNA expressions in inflammation | N/A | [27] |
Naringin | ||||||
0.1 µM | Hydroperoxide | Adipose tissue | Osteogenic differentiation | Reversed the H2O2-induced decrease in ALP activity, osteogenic gene expression (Runx2, Osx) | Wnt/β-catenin ↑ | [52] |
0.1 µM | TNF-α | Bone marrow | Osteogenic differentiation | Rescued the TNF-α-induced decrease in ALP activity, osteogenic gene expression (Runx2, Osx) | NF-κB↓ | [51] |