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| Active ingredients | Differentiated cells | Stem cells or model | Pathways | Effects | References |
|
| Astragaloside IV | Endothelial cell-like cells | Rat mesenchymal stem cells | N/A | 1. Differentiated into endothelial cell-like cells and promoted tube formation in vitro
2. Upregulated the expression of Cx37, Cx40, and Cx43 and enhanced gap junctional intercellular communication (GJIC) function | [22] |
| Neuronal cells | Rat neural stem cells | Sonic hedgehog | 1. Differentiation into dopamine neurons
2. Promoted the expressions of Shh, Nurr1, and Ptx3 mRNAs | [14] |
|
| Astraisoflavan | Neuronal cells | Rat neural stem cells | Sonic hedgehog | 1. Differentiation into dopamine neurons
2. Promoted the expressions of Shh, Nurr1, and Ptx3 mRNAs | [14] |
|
| Aucubin | Neuronal cells | Rat neural stem cells and neural precursor cells | N/A | 1. Promoted lengthening and thickness of axons and remyelination at 3 weeks after sciatic nerve injury
2. Promoted differentiation of neural precursor cells into GABAergic neurons | [16, 17, 129] |
|
| Baicalin | Cardiomyocytes | Murine embryonic stem cells | N/A | 1. Increased the proportion of a-actinin-positive cardiomyocytes
2. Upregulated cardiac specific genes a-MHC, MLC-2v, and ANP | [36] |
| Neuronal cells | Neural stem cells derived from the cortex of embryonic E15-16 SD rats | N/A | 1. Increased the percentages of mature neuronal marker MAP-2-positive staining cells and decreased glial marker GFAP staining cells
2. Downregulated the expression of p-stat3 and Hes1 but upregulated the expressions of NeuroD1 and Mash1 | [13] |
| Osteoblasts | N/A | Wnt/β-catenin signaling | 1. Increased significantly the osteoblastic mineralization levels of mRNAs encoding the bone differentiation markers OCN, OPN, and COL-1 | [54] |
|
| Bavachalcone | Endothelial cells | Rat bone marrow mesenchymal stem cells and rat hindlimb ischemia model | RORα-erythropoietin-AMPK axis | 1. Promoted rat bone marrow-derived cells to differentiate into EPC significantly
2. Stimulated blood flow recovery in ischemic hindlimbs, increased circulating EPC, and promoted capillary neovascularization | [19] |
|
| Berberine | Osteoblasts | Bone marrow-derived mesenchymal stem cells | Wnt/β-catenin signaling | Promoted osteogenic differentiation and osteogenic genes Runx2, OPN, and OCN expression | [132] |
|
| Catalpol | Osteoblasts | Bone marrow mesenchymal stem cells | Wnt/β-catenin signaling | 1. Enhances the osteogenic differentiation
2. Significantly enhanced osteoblast-specific gene expression, alkaline phosphatase activity, and calcium deposition | [53] |
|
| Curcumin | Cardiomyocytes | Human embryonic stem cells | NO-cGMP signaling | 1. Promoted differentiation into cardiomyocytes
2. Significantly increased the gene expression and protein levels of NKX2.5, cTNI, MHCs, and eNOS | [96] |
|
| Ginkgolide B | Endothelial progenitor cells | Human bone marrow | Akt/eNOS and p38 MAPK signaling | 1. Promoted proliferation and endothelial gene expression, significantly enhanced VEGF-induced migration response, and improved the vascular network composition of EPCs
2. Induced phosphorylation of eNOS, Akt, and p38 | [20] |
| Neuronal cells | Neural stem cells derived from mouse subventricular zone (SVZ) | Wnt/β-catenin | 1. Promoted neuronal differentiation
2. Increased the level of nuclear β-catenin and activated the Wnt pathway | [15] |
| Osteoblasts | Rat bone mesenchymal stem cells and MC3T3-E1 cells | Wnt signaling | 1. Promotes osteoblast differentiation
2. Reduced OVX-induced bone loss by enhancing osteoblast activity | [51] |
|
| Ginsenoside Rb1/RE | Cardiomyocytes | Human embryonic stem cell | N/A | 1. Enhanced differentiation into cardiomyocytes
2. Upregulated Nkx2.5, Tbx5, MHC, and KCNE1 expression | [32] |
|
| Ginsenoside Rg1 | Neuronal cells | Mouse embryonic stem cells and human adipose-derived stem cells | Wnt/β-catenin pathway, MEK-ERK1/2, and PI3K-Akt signaling | 1. Promoted cell proliferation and neural phenotype differentiation
2. Upregulated the mRNA or protein expression of NSE, MAP-2, NEFM, NCAM, synapsin-1, and β-tubulin III | [4, 5] |
|
| Ginsenoside RH2 (S) | Osteoblasts | MC3T3-E1 cells | PKD/AMPK signaling | 1. Stimulated osteoblastic differentiation and mineralization
2. Enhanced the expression of Runx2, ALP, OCN, OPN, Osx, and ColI | [103] |
|
| icariin | Cardiomyocytes | Mouse embryonic stem cells | p38 MAPK pathway in early differentiation and NO-cGMP signaling | 1. Facilitated the directional differentiation of ES cells into cardiomyocytes
2. Elevated PGC-1-alpha, PPAR-alpha, and NRF-1 expression in early differentiation
3. Increased mRNA level of MHC, MLC-2v, α-actinin, and troponin T | [29–31, 95, 102] |
| Osteoblasts | Rat bone mesenchymal stem cells | ERα-Wnt/β-catenin signaling, RhoA-TAZ signaling, and AKT-eNOS-cGMP pathway | 1. Significantly enhanced osteogenic differentiation and increased ALP activity and Lef1, TCF7 DLX5, OPN, OCN, COLI, ERα, CXCR4, and HIF-1α expression
2. Upregulated TAZ, Runx2, β-catenin, OPN, and Dlx5 expression mainly at the early stage and OCN expression at the late stage
3. Improved osteoporosis, inhibited the expression of PPARγ, C/EBPα, FABP4 mRNA, N1ICD, and Jagged1 proteins and increased Notch2 mRNA in OVX rats | [39–42, 55, 86, 89, 94] |
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| Kaempferol | Osteoblasts | Rat bone mesenchymal stem cells | Interaction between TAZ and RUNX2 | Promoted physical interaction between TAZ and RUNX2 to increase osteoblast differentiation of mesenchymal cells | [43] |
|
| Ligustilide | Osteoblasts | MC3T3-E1 cells and rat bone mesenchymal stem cells | GPR30/EGFR pathway | 1. Promoted osteoblast differentiation
2. Activated phosphorylated EGFR and ERK1/2 | [45] |
|
| Myricetin | Osteoblasts | Human bone marrow stem cells and human periodontal ligament stem cells | Wnt/β-catenin pathway, BMP-2/Smad, and ERK/JNK/p38 MAPK | 1. Enhanced osteogenic differentiation
2. Upregulated BMP-2
3. Increased mRNA expression of OCN, COL-1, ALP, and RUNX2 | [130, 131] |
|
| Polydatin | Osteoblasts | Human bone marrow stromal cells and OVX mouse model | BMP-2-Wnt/β-catenin signaling | 1. Significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2, OPN, DLX5, β-catenin, TAZ, and OCN
2. Maintained the bone matrix in the OVX mouse model | [47] |
|
| Puerarin | Osteoblasts | Rat bone marrow stromal cells | Estrogen receptor-dependent manner | 1. Enhanced osteoblast differentiation
2. Increased ALP activity, OCN, and Wnt5b | [50, 93] |
| Quercetin | Osteoblasts | Human adipose tissue-derived stromal cells, mouse adipose stem cells, rat mesenchymal stem cells, and rat bone marrow-derived mesenchymal stem cells | p38 MAPK, ERK1/2 and JNK MAPK signaling | 1. Promoted the osteogenic differentiation
2. Promoted expressions of ALP, Osx, Runx2, BMP-2, TGF-β1, Col-1, OPN, and OCN | [134–137] |
|
| Resveratrol | Neuronal-like cells | Human bone marrow mesenchymal stem cells and human cord blood-derived mesenchymal stem cells | Sonic hedgehog signaling, PKA-GSK3β, and β-catenin signaling | 1. Differentiated into neuronal-like cell types
2. Significantly increased expression of the neuronal-specific marker genes Nestin, Musashi, CD133, GFAP, NF-M, MAP-2, and KCNH1
3. Increased expressions of Smo and Gli1 proteins | [75, 138–140] |
| Osteoblasts | Mouse embryonic stem cells, rat adipose-derived mesenchymal stem cells | AMPK/Ulk1 pathway, and Sirt-1/Runx2 deacetylation | 1. Enhancing osteogenic differentiation and mineralization
2. Enhanced expression of pluripotency markers Oct3/4, Sox2, Nanog, Klf4, SSEA-1, and ALP
3. Increased expression of Runx2 and decreased expression of PPAR-γ | [104, 141, 142] |
|
| Salidroside | Neuronal cells | Rat bone marrow mesenchymal stem cells, mouse mesenchymal stem cells | Notch and BMP signaling pathways | 1. Inhibited the proliferation, increased expression level of NSE, BDNF, MAP2, β-tubulin III, GFAP, Wnt3a, β-catenin, LRP6, and Axin
2. The positive rate of Ach was significantly higher on the 3rd, 6th, and 9th day than on the 1st day | [18, 56, 82] |
|
| Salvianolic acid a/B | NF-M (+) neurons and NG2 (+) oligodendrocyte precursors | Neural stem cells derived from the cerebral cortex of embryonic mice, bone marrow-derived neural stem cells, and induced pluripotent stem cells | PI3K/AKT/GSK3β/β-catenin pathway | 1. Promoted the neurite outgrowth of neural stem cells and their differentiation into neurons
2. Induced BDNF production | [8, 143, 144] |
| Osteoblasts | Human mesenchymal stem cells and rat bone marrow stromal stem cells | ERK signaling and NO-cGMP signaling | 1. Significantly promoted mineralization
2. Increased ALP activity, Runx2, osterix, OPG, and OCN level and the OPG/RANKL ratio | [46, 97] |
| Hepatocytes | Human embryonic stem cells | Through upregulation of WNT pathway and inhibition of Notch pathway | 1. Promoted hepatocyte differentiation and increased expression of albumin, tyrosine aminotransferase (TAT), CYP3A4, CYP2C19, UGT1A6, UGT1A8, and UGT2B7
2. Enhanced expression of TCF3 and LEF1 and downregulated Jagged2, and Hes1/5 | [57] |
| Alveolar epithelial cells type I | Rat bone marrow mesenchymal stem cells | WNT pathway | 1. By day 14, the majority of bone marrow mesenchymal stem cells were morphologically differentiated into alveolar epithelial cells
2. Significantly increased the T1α and AQP-5 protein levels | [58] |
|
| Silibinin | Osteoblasts | Human bone marrow stem cells | Activating BMP and RUNX2 pathways | 1. Promoted ALP activity and mineralization in hBMSCs
2. Increased the mRNA expressions of COLI, ALP, OCN, osterix, BMP-2, and RUNX2 | [133] |
|
| Tanshinone IIA | Neuronal-like cells | Rat bone marrow mesenchymal stem cells | N/A | Significantly upregulated the expression levels of Nestin, NeuN, and NF200 in the transplanted cells in the BMSCs + tanshinone IIA treatment rats compared among the groups | [10] |
| Osteoblasts | Mouse bone marrow mesenchymal stem cells and human periodontal ligament stem cells | ERK1/2-dependent Runx2 induction and BMP-Wnt signaling | 1. Enhanced ALP activity on day 7 and calcium content on day 24 in the process of TSA-induced osteogenesis of mouse bone marrow mesenchymal stem cells
2. Promoted both osteogenic differentiation and maturation of periodontal ligament stem cells | [48, 70, 100] |
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| 2,3,5,4’- Tetrahydroxy- stilbene-2-O-β-D-glucoside (THSG) | Osteoblasts | Rat mesenchymal stem cells | N/A | Promoted osteogenic differentiation and increased ALP activity and OCN expression | [52] |
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