The Promotion of Cell Proliferation by Food-Derived Bioactive Peptides: Sources and Mechanisms
Abstract
1. Introduction
2. Source and Preparation of Cell Proliferation-Promoting Peptides
2.1. Cell Proliferation-Promoting Peptides Derived from Aquatic Animals
Sequence | Source | Cell/Animal Model | Amount Added | Action Pathway | Cell Performance | Animal Performance | References |
---|---|---|---|---|---|---|---|
YRGDVVPK | Oyster | Mouse embryo osteoblast precursor cell (MC3T3-E1) | 100 nM | MAPK signaling pathway | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [9] |
TPERYY | Tilapia scale | MC3T3-E1 cell | 109 μg/mL | Wnt/β-catenin signaling pathway | Cell proliferation, differentiation, and mineralization ↑ | Bone health ↑ Osteoporosis ↓ | [7] |
KSA | Johnius belengerii | MC3T1-E1 cell | — | MAPK signaling pathway | Cell proliferation and differentiation ↑ | Osteoporosis ↓ bone formation ↑ | [23] |
YPRKDETGAERT | Mytilus edulis | MC3T3-E1 cell | Bone morphogenetic protein type 2 (BMP-2) signaling pathway | Cell proliferation and differentiation ↑ | Femoral ↑, osteoporosis ↓ | [31] | |
SCIH (28 peptides) | Sea Cucumber Intestine | MC3T3-E1 cell | 25 μg/mL | Wnt/β-catenin signaling pathway | Cell proliferation and differentiation ↑ | Bone growth ↑ | [29] |
RPQYPQYPS, LSFSPY | Sea cucumber | MC3T3-E1 cell | 100 μg/mL | — | Proliferation and mineralization ↑ | Osteoporosis ↓ | [32] |
FDNEGKGKLPEEY, FWDGRDGEVDGFK VLQTDNDALGKAK IVLDSGDGVTH, MVAPEEHP | Pinctada martensii | MC3T3-E1 cell | 2 μg/mL | — | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [33] |
WSMP | Oyster shells | MC3T3-E1 cell | 100 μg/mL | BMP-2 signaling pathway | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [34] |
MNKKREAEFQ | Gadus morhua | MC3T3-E1 cell | 100 μg/mL | BMP/WNT signaling pathway | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [35] |
— | Chanos chanos | Human osteosarcoma cell (MG-63) | 100 μg/mL | — | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [36] |
— | Mytilus coruscus | Mouse Mononuclear Macrophage cell (RAW264.7) | 100 μg/mL | MAPK signaling pathway | Cell proliferation ↑, the phagocytosis of cells ↑ | Immunomodulation ↑ | |
— | Nibea japonica | Mouse Embryonic Fibroblast cell (NIH-3T3) | 25 μg/mL | NF-κB signaling pathway | Cell proliferation and migration ↑ | Wound healing ↑ | [14] |
— | Sipunculus nudus | HUVEC, Human immortalized epidermal cells (HaCaT), HSF cell | — | — | Cell proliferation ↑ | Wound healing ↑, scar formation ↓ | [28] |
VTPY, VLLY | Sea cucumber | HSF cell and HUVEC cell | 1000 nmol/mL | ERK/AKT signaling pathway | Cell proliferation ↑ | Wound healing ↑ | [12] |
NINECFSSPCEN OGICODEIDGYN CVCOPGFTGTHCE | Sea cucumber | Human melanoma cell | 10 nM | MAPK and AKT signaling pathway | Cell proliferation ↑ | Wound healing ↑ | [3] |
QIGFIW, IGIGPSGAS | Bigbelly seahorse | Mouse myoblast cell (C2C12) | 100 μg/mL | P38MAPK/AKT signaling pathway | Cell proliferation and differentiation ↑ | Skeletal muscle differentiation and endurance ↑ | [37] |
VGRTNSH | Oyster | Human normal breast cell (MCF-10A) | 50 μg/mL | PRL/AKT/STAT5 and Mammalian target of rapamycin (mTOR)/Ribosomal protein S6 kinase B1 (S6KB1) signaling pathway | Cell proliferation ↑ | Lactation ↓ | [38] |
— | Coryphaena hippurus | bone marrow-derived macrophage cell (BMMS) | 50 ng/mL | MAPK signaling pathway | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [27] |
— | Mozambique tilapia | Human dermal papilla cells (hDPC) | 62.5 ppm | Wnt/β-catenin signaling pathway | Cell proliferation ↑ | Hair growth in the back skin tissue ↑ | [22] |
MGLAGPR, MGDVLNF, EAPLMHV, TEAPLMHV, TEAPLMHV | Octopus | Mouse mammary epithelial cell (HC11) | 25 μg/mL | — | Cell proliferation ↑ | The synthesis of β-casein ↑ | [39] |
2.2. Cell Proliferation-Promoting Peptides Derived from Plants
Sequence | Source | Cell/Animal Model | Amount Added | Action Pathway | Cell Performance | Animal Performance | References |
---|---|---|---|---|---|---|---|
IQDKEGIPPDQQR | Extruded Lupin | RAW 264.7 cell | 1 μg/mL | MARK signaling pathway | Cell proliferation ↑ | Inflammatory response ↓ | [20] |
— | Mung bean | RAW264.7 cell | 200 mg/mL | — | Cell proliferation ↑, phagocytosis ↑ | Immunomodulation ↑ and anti-inflammation | [47] |
YGPSSYGYG | Pseudostellaria heterophylla | RAW264.7 cell | 200 μg/mL | Toll-like receptors (TLR)/NF-κB/TNF-αsignaling pathway | Cell proliferation ↑, the endocytosis of macrophages ↑ | Immunomodulation ↑ | [21] |
SSFSKGVQRAAF | Rice bran | HUVEC cell | 1 μM | — | Cell proliferation and migration ↑ | Wound healing ↑ | [46] |
DIGGL | Ulva prolifera | HUVECs cell | 100 μM | — | Cell proliferation ↑ | Immunomodulation ↑ blood pressure ↓ | [43] |
LRW | Pea | MC3T3-E1 cell | 50 μM | PI3K/AKT, AKT/Runx2 signal pathway | Cell proliferation, migration, differentiation, and mineralization ↑ | Osteoclast formation and the prevention of osteoporosis ↓ | [8] |
DEDEQIPSHPPR | Soybean | MC3T3-E1 cell | 70 μM | MAPK signaling pathway | Cell proliferation, differentiation, and mineralization ↑ | Osteoporosis ↓ | [48] |
— | Zein peptides | C2C12 cells | 200 μg/mL | Mechanistic Target of Rapamycin Complex 1/2 (mTORC1/mTORC2) signaling pathway | Cell proliferation and cell cycle progression ↑ | Sarcopenia ↓ | [49] |
NQLDQMPR, PVNKPGRFE and the other 52 peptides | Soybean | Rat small intestine crypt epithelial cell (IEC-6) | 1 mg/mL | — | Cell proliferation ↑ | Intestinal inflammation ↓ | [45] |
— | Porphyra haitanensis | IEC-6 cell | 100 μg/mL | — | Cell proliferation and migration ↑ | Intestinal epithelial wound healing ↑ | [44] |
— | Cornus officinalis | Chicken Embryonic Fibroblasts (CEF) | 0.4 mg/mL | — | Cell proliferation ↑ | Free radicals ↓, anti-oxidation | [50] |
SKWQHQQDSCRKQGVNLTPCEKHIMEKIQGRGDDDDDDDDD | Seed peptide | Male C57BL/6Jnarl mice, EL-4 T cell | — | — | Cell proliferation ↑, cytokines ↑ | Anti-inflammatory, antioxidant ↑ | [40] |
2.3. Cell Proliferation-Promoting Peptides Derived from Livestock Products
3. Cell Proliferation-Promoting Mechanism of Peptides
3.1. Signal Pathway
3.1.1. MAPK Signaling Pathway
3.1.2. Wnt/β-Catenin Signaling Pathway
3.1.3. NF-κB Signaling Pathway
3.1.4. PI3K/AKT Signaling Pathway
3.1.5. BMP Signaling Pathway
3.2. Regulation of Energy Metabolism
3.3. Cell Cycle Regulation
3.4. Regulation of Cytokines and Growth Factors
4. Safety and Regulatory Framework for Promoting Cell Proliferation Peptides
5. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ECM | Extracellular matrix |
HUVEC | Human umbilical vein endothelial cells |
TOF | Time-of-flight |
HPLC-MS/MS | High-performance liquid chromatography-tandem mass spectrometry |
MSCs | Mesenchymal stem cells |
BMSCs | Bone marrow-derived mesenchymal stem cells |
OCR | Oxygen consumption rate |
COX2 | Cyclooxygenase-2 |
NRF-1 | Nuclear respiratory factor 1 |
TFAM | Mitochondrial transcription factor A |
AKT | Protein kinases (ERK) and protein kinase B |
TGF-α | Transforming growth factor-α |
MAPK | Mitogen-activated protein kinase |
NF-κB | Nuclear factor κ-B |
IKKα | IκB kinase α |
FGF | Fibroblast growth factor |
EGF | Epidermal growth factor |
VEGF | Vascular endothelial growth factor A |
MCPs | Marine collagen peptides |
CFDA | China Food and Drug Administration |
IGF-1R | Insulin-like growth factor 1 receptor |
ERK1/2 | Extracellular regulated protein kinases 1/2 |
SMAD | Mothers against decapentaplegic |
PI3K | Phosphoinositide 3-kinase |
LRP1 | LDL receptor-related protein 1 |
PGE2 | Prostaglandin E2 |
IL-6 | Interleukin-6 |
BMP-2 | Bone morphogenetic protein type 2 |
S6KB1 | Ribosomal protein S6 kinase B1 |
mTOR | Mammalian target of rapamycin |
TLR | Toll-like receptors |
RAW264.7 | Mouse mononuclear macrophage cells |
MC3T3-E1 | Mouse embryo osteoblast precursor cells |
mTORC1/mTORC2 | Mechanistic target of rapamycin complex 1/2 |
HaCaT | Human immortalized epidermal cells |
JNK | c-Jun N-terminal kinase |
ERK | Extracellular-regulated protein kinases |
AP-1 | Activator protein 1 |
MyoD | Myogenic differentiation antigen |
MyoG | Myogenin |
MyHC | Myosin heavy chain |
GSK3β | Glycogen synthase kinase 3 beta |
LRP5/6 | Low-density lipoprotein receptor-related proteins 5 and 6 |
UPLC | Ultra-Performance Liquid Chromatography |
TCF/LEF | T cell factor/lymphoid enhancer factor family |
LRP3 | Low-density lipoprotein receptor-related protein 3 |
IκB | Inhibitor of NF-κB |
ROS | Reactive oxygen species |
MEK | Mitogen-activated extracellular signal-regulated kinase |
PIP3 | Phosphatidylinositol-3,4,5-trisphosphate |
PTEN | Phosphatase and tensin homolog |
GAB1 | GRB2-associated binder 1 |
PDK1 | Pyruvate dehydrogenase kinase 1 |
GSK-3 | Glycogen synthase kinase-3 |
BMP | Bone morphogenetic protein |
ATP | Adenosine triphosphate |
MCF-10A | Human normal breast cells |
HO-1 | Heme oxygenase-1 |
EGFR | Epidermal growth factor receptor |
Nrf-2 | Nuclear factor erythroid 2-related factor 2 |
NIH-3T3 | Mouse embryonic fibroblast cells |
TNF-α | Tumor necrosis factor alpha |
TGF-β | Transforming growth factor-β |
MG-63 | Human osteosarcoma cell |
HSF | human skin fibroblast |
BMMS | Bone marrow-derived macrophage cell |
hDPC | Human dermal papilla cells |
IEC-6 | Intestine crypt epithelial cell |
CEF | Chicken embryonic fibroblast cell |
GSK-3β | Glycogen synthase kinase 3 beta |
IKKβ | IκB kinase β |
PIP2 | Phosphatidylinositol 4,5-bisphosphate |
BMP-2/4 | Bone morphogenetic proteins-2/4 |
SMAD1/5 | Mothers against decapentaplegic homolog 1/5 |
BMP-2/4 | Bone morphogenetic protein 2/4 |
ADP | Adenosine diphosphate |
IGF-1 | Insulin-like growth factor-1 |
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Sequence | Source | Cell/Animal Model | Amount Added | Action Pathway | Cell Performance | Animal Performance | References |
---|---|---|---|---|---|---|---|
FKSETKNLL | Bovine lactoferrin | MC3T3-E1 cell | 200 μg/mL | MAPK signaling pathway | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [51] |
VSEE | Duck Egg White | MC3T3-E1 cell | 1 mM | Wnt/β-catenin signaling pathway | Cell proliferation, differentiation, and mineralization ↑ | Osteoporosis ↓, dyslipidemia ↓ | [6] |
— | Porcine bone | MC3T3-E1 cell | 0.5 mg/mL | PI3K/AKT signaling pathway | Cell proliferation and differentiation ↑, Cell cycle progression ↑ | Osteoporosis ↓ | [55] |
GPAGPPGPIGNV | Yak bones | MC3T3-E1 cell | 60.6 mg/mL | Wnt/β-catenin signaling pathway | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [56] |
GPAGPSGPAGK, GPPGSPGPR | Bovine Gelatin | MC3T3-E1 cell | 3 mg/mL | MAPK/ERK1/2 signaling pathway | Cell proliferation, differentiation, and mineralization ↑ | Osteoporosis ↓ Osteoarthritis ↓ | [30] |
— | Whey protein | MC3T3-E1 cell | 500 μg/mL | — | Cell proliferation, differentiation, and mineralization ↑ | Osteoporosis ↓protects bones | [57] |
ARHPHPHLSF, AAGGPGAPADPGRPTGY, NIPPLTQTPVVVPPFLQPE | Fermented milk | MC3T3-E1 cell | 2 μM | MAPK signaling pathway | Cell proliferation, differentiation, and mineralization ↑ | Osteoporosis ↓protects bones | [5] |
HHGDQGAPGAVGPAGPRGPAGPSGPAGKDGR, GPAGANDRGEAGPAGPAGPR | Bovine Bone | MC3T3-E1 cell | 48.0 mg/mL | — | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [54] |
PASTGAAK, PGPPGTPF | black-boned silky fowl | MC3T3-E1 cell | 400 μg/mL | BMP-2/Smad signaling pathway | Cell proliferation and differentiation ↑ | Osteoporosis ↓ | [58] |
VLVLDTDYKK, VGINYWLAHK | Whey protein | RAW 264.7 cell | 1.25 mg/mL | — | Cell proliferation ↑ | Free radicals ↓, anti-inflammatory | [53] |
COLPROPURD | Porcine fresh bones | Monocytic, lymphocyte, and Caco-2 | 0.15 mg/mL, 1.4 mg/mL,137.5 μg/mL | — | Cell proliferation ↑ and cytokine ↑ | Anti-intestinal inflammation, immunomodulation ↑ | [18] |
EF, AGGF, EHPT | Black-bone silky fowl | Mice spleen | 1 mM | — | Lymphocyte proliferation ↑ | Immunomodulation ↑ | [52] |
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Yan, Y.; Liu, Y.; Zhang, X.; Zan, L.; Fang, X. The Promotion of Cell Proliferation by Food-Derived Bioactive Peptides: Sources and Mechanisms. Metabolites 2025, 15, 505. https://doi.org/10.3390/metabo15080505
Yan Y, Liu Y, Zhang X, Zan L, Fang X. The Promotion of Cell Proliferation by Food-Derived Bioactive Peptides: Sources and Mechanisms. Metabolites. 2025; 15(8):505. https://doi.org/10.3390/metabo15080505
Chicago/Turabian StyleYan, Yuhao, Yinuo Liu, Xinwei Zhang, Liting Zan, and Xibi Fang. 2025. "The Promotion of Cell Proliferation by Food-Derived Bioactive Peptides: Sources and Mechanisms" Metabolites 15, no. 8: 505. https://doi.org/10.3390/metabo15080505
APA StyleYan, Y., Liu, Y., Zhang, X., Zan, L., & Fang, X. (2025). The Promotion of Cell Proliferation by Food-Derived Bioactive Peptides: Sources and Mechanisms. Metabolites, 15(8), 505. https://doi.org/10.3390/metabo15080505