journal article·2025-07-23Open access

Effects of Epigallocatechin-3-O-Gallate on Bone Health

Patrycja Wróbel, Beata Czarczynska-Goslinska, Kyrylo Chornovolenko, Julia Liwarska, Jakub Kubiak, Tomasz Koczorowski, Agnieszka Malinska, Tomasz Goslinski, Magdalena Waszyk-Nowaczyk

Applied Sciences· Volume 15· Issue 15

Abstract

Tea is one of the most consumed beverages in the world, belonging to the category of compounds known as tannins and flavonoids. One of the polyphenols found in large amounts in green tea leaves (Camellia sinensis) is epigallocatechin-3-O-gallate (EGCG). Though EGCG has shown some pharmacological effects, to date, it has not been utilised as a therapeutic agent. This is attributed to the fact that EGCG lacks adequate stability, and it is known to degrade through epimerization or auto-oxidation processes, especially when it is exposed to light, temperature fluctuations, some pH values, or the presence of oxygen. Consuming green tea with EGCG can alleviate the effects of bone diseases, such as osteoporosis, and support faster bone regeneration in the case of fractures. Therefore, this review focuses on the current state of research, highlighting the effects of EGCG on bone biology, such as enhancing osteoblast differentiation, promoting bone mineralisation, improving bone microarchitecture, and inhibiting osteoclastogenesis through the modulation of the RANK/RANKL/OPG pathway. Additionally, EGCG exerts antioxidant, anti-inflammatory, and dose-dependent effects on bone cells. It also downregulates inflammatory markers (TNF-α, IL-1β, and COX-2) and reduces oxidative stress via the inhibition of reactive oxygen species generation and the activation of protective signalling pathways (e.g., MAPK and NF-κB). Studies in animal models confirm that EGCG supplementation leads to increased bone mass and strength. These findings collectively support the further exploration of EGCG as an adjunct in the treatment and prevention of metabolic bone diseases. The authors aim to present the relationship between EGCG and bone health, highlighting issues for future research and clinical applications.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Bone Metabolism and Diseases · Tea Polyphenols and Effects · Curcumin's Biomedical Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Chair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland

Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland

Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznań, Poland

Pharmacy Practice and Pharmaceutical Care Division, Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland

Chair and Department of Histology and Embryology, Poznan University of Medical Sciences, Święcickiego 6, 60-781 Poznań, Poland

Funding

National Science Centre, Poland

References (100+)

Show source-provided references
1. Green Tea Catechin, Epigallocatechin-3-Gallate (EGCG): Mechanisms, Perspectives and Clinical Applications10.1016/j.bcp.2011.07.093 ↗
2. Targeting Multiple Signaling Pathways by Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate10.1158/0008-5472.CAN-05-3636 ↗
3. Mokra, D., Joskova, M., and Mokry, J. (2022). Therapeutic Effects of Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG) in Relation to Molecular Pathways Controlling Inflammation, Oxidative Stress, and Apoptosis. Int. J. Mol. Sci., 24.10.3390/ijms24010340 ↗
4. Green Tea Polyphenols Mitigate Deterioration of Bone Microarchitecture in Middle-Aged Female Rats10.1016/j.bone.2008.11.018 ↗
5. Farhan, M. (2022). Green Tea Catechins: Nature’s Way of Preventing and Treating Cancer. Int. J. Mol. Sci., 23.10.3390/ijms231810713 ↗
6. Antioxidant Capacity and Major Polyphenol Composition of Teas as Affected by Geographical Location, Plantation Elevation and Leaf Grade10.1016/j.foodchem.2017.09.126 ↗
7. Detection and Chemical Identification of Natural Bio-Antimutagens: A Case of the Green Tea Factor10.1016/0027-5107(85)90109-5 ↗
8. Jin, J.-Q., Jiang, C.-K., Yao, M.-Z., and Chen, L. (2020). Baiyacha, a Wild Tea Plant Naturally Occurring High Contents of Theacrine and 3″-Methyl-Epigallocatechin Gallate from Fujian, China. Sci. Rep., 10.10.1038/s41598-020-66808-x ↗
9. Liu, Y., Long, Y., Fang, J., and Liu, G. (2024). Advances in the Anti-Atherosclerotic Mechanisms of Epigallocatechin Gallate. Nutrients, 16.10.3390/nu16132074 ↗
10. Epigallocatechin Gallate in Relapsing-Remitting Multiple Sclerosis10.1212/NXI.0000000000000981 ↗
11. Platero, J.L., Cuerda-Ballester, M., Ibáñez, V., Sancho, D., Lopez-Rodríguez, M.M., Drehmer, E., and de la Rubia Ortí, J.E. (2020). The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients. Nutrients, 12.10.3390/nu12020305 ↗
12. Polyphenon E, Non-Futile at Neuroprotection in Multiple Sclerosis but Unpredictably Hepatotoxic: Phase I Single Group and Phase II Randomized Placebo-Controlled Studies10.1016/j.jns.2015.08.006 ↗
13. Jing, F., Zhu, L., Bai, J., Cai, X., Zhou, X., Zhang, J., Zhang, H., and Li, T. (2023). Molecular Mechanisms Underlying the Epigallocatechin-3-Gallate-Mediated Inhibition of Oral Squamous Cell Carcinogenesis. Arch. Oral Biol., 153.10.1016/j.archoralbio.2023.105740 ↗
14. An EGCG-Mediated Self-Assembled Micellar Complex Acts as a Bioactive Drug Carrier10.1016/j.foodchem.2023.135939 ↗
15. Potential Neuroprotective Properties of Epigallocatechin-3-Gallate (EGCG)10.1186/s12937-016-0179-4 ↗
16. The Protective Effects of EGCG Was Associated with HO-1 Active and Microglia Pyroptosis Inhibition in Experimental Intracerebral Hemorrhage10.1016/j.neuint.2023.105603 ↗
17. Potential Protective Function of Green Tea Polyphenol EGCG against High Glucose-Induced Cardiac Injury and Aging10.1016/j.jff.2023.105506 ↗
18. Effects of Epigallocatechin-3-Gallate on Oxidative Stress, Inflammation, and Bone Loss in a Rat Periodontitis Model10.1016/j.jds.2023.02.019 ↗
19. Chen, S.-T., Kang, L., Wang, C.-Z., Huang, P.-J., Huang, H.-T., Lin, S.-Y., Chou, S.-H., Lu, C.-C., Shen, P.-C., and Lin, Y.-S. (2019). (−)-Epigallocatechin-3-Gallate Decreases Osteoclastogenesis via Modulation of RANKL and Osteoprotegrin. Molecules, 24.10.3390/molecules24010156 ↗
20. The Effect of Orally Administered Epigallocatechin-3-gallate on Ligature-induced Periodontitis in Rats10.1111/jre.12071 ↗
21. Lin, S.-Y., Kan, J.Y., Lu, C.-C., Huang, H.H., Cheng, T.-L., Huang, H.-T., Ho, C.-J., Lee, T.-C., Chuang, S.-C., and Lin, Y.-S. (2020). Green Tea Catechin (-)-Epigallocatechin-3-Gallate (EGCG) Facilitates Fracture Healing. Biomolecules, 10.10.3390/biom10040620 ↗
22. Potential Protective Mechanisms of Green Tea Polyphenol EGCG against COVID-1910.1016/j.tifs.2021.05.023 ↗
23. Diet and Lifestyle Associated with Increased Bone Mineral Density: Cross-Sectional Study of Japanese Elderly Women at an Osteoporosis Outpatient Clinic10.1007/s00776-007-1143-0 ↗
24. Epigallocatechin Gallate (EGCG) Can Epigenetically Regulate the Receptor of Advanced Glycation End Products (RAGE) to Ameliorate Osteoarthritis10.1016/j.jff.2023.105682 ↗
25. Zou, J., Chen, F., Li, Y., Chen, H., Sun, T., Du, S., and Zhang, J. (2023). Effects of Green Tea Extract Epigallocatechin-3-Gallate (EGCG) on Orthodontic Tooth Movement and Root Resorption in Rats. Arch. Oral Biol., 150.10.1016/j.archoralbio.2023.105691 ↗
26. Green Tea Catechin Enhances Osteogenesis in a Bone Marrow Mesenchymal Stem Cell Line10.1007/s00198-005-1995-0 ↗
27. (−)-Epigallocatechin Gallate Inhibits Prostaglandin D2-Stimulated HSP27 Induction via Suppression of the P44/P42 MAP Kinase Pathway in Osteoblasts10.1016/j.plefa.2007.09.001 ↗
28. Implantation of Green Tea Catechin α-Tricalcium Phosphate Combination Enhances Bone Repair in Rat Skull Defects10.1002/jbm.b.31848 ↗
29. Liu, J., Lu, Y., Liu, J., Jin, C., Meng, Y., and Pei, D. (2019). Influence of Epigallocatechin-3-Gallate in Promoting Proliferation and Osteogenic Differentiation of Human Periodontal Ligament Cells. BMC Oral Health, 19.10.1186/s12903-019-0768-7 ↗
30. The Effect of Epigallocatechin-3-Gallate (EGCG) on Human Alveolar Bone Cells Both in Vitro and in Vivo10.1016/j.archoralbio.2014.02.011 ↗
31. Role of (-)-Epigallocatechin-3-Gallate in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells: An Enhancer or an Inducer?10.3892/etm.2015.2579 ↗
32. The Effects of Epigallocatechin-3-Gallate and Mechanical Stimulation on Osteogenic Differentiation of Human Mesenchymal Stem Cells: Individual or Synergistic Effects10.1007/s13770-017-0040-7 ↗
33. Epigallocatechin-3-Gallate Protects against Tumor Necrosis Factor Alpha Induced Inhibition of Osteogenesis of Mesenchymal Stem Cells10.1177/1535370215624020 ↗
34. (−)-Epigallocatechin Gallate Reduces Transforming Growth Factor β-Stimulated HSP27 Induction through the Suppression of Stress-Activated Protein Kinase/c-Jun N-Terminal Kinase in Osteoblasts10.1016/j.lfs.2008.02.017 ↗
35. (−)-Epigallocatechin-3-Gallate Improves Bone Microarchitecture in Ovariectomized Rats10.1097/GME.0b013e31828244f0 ↗
36. Fenton Reaction Is Primarily Involved in a Mechanism of (−)-Epigallocatechin-3-Gallate to Induce Osteoclastic Cell Death10.1006/bbrc.2002.6622 ↗
37. Inhibitory Effects of Green Tea Polyphenol (-)-Epigallocatechin Gallate on the Expression of Matrix Metalloproteinase-9 and on the Formation of Osteoclasts10.1111/j.1600-0765.2004.00743.x ↗
38. Green tea polyphenol (-)-epigallocatechin gallate suppressed the differentiation of murine osteoblastic MC3T3-E1 cells10.1042/CBI20090011 ↗
39. Repression of IGF-I-Induced Osteoblast Migration by (-)-Epigallocatechin Gallate through P44/P42 MAP Kinase Signaling
40. Epigallocatechin-3-Gallate Protects against Hydrogen Peroxide-Induced Inhibition of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells10.1155/2016/7532798 ↗
41. Lin, S.-Y., Kang, L., Wang, C.-Z., Huang, H., Cheng, T.-L., Huang, H.-T., Lee, M.-J., Lin, Y.-S., Ho, M.-L., and Wang, G.-J. (2018). (−)-Epigallocatechin-3-Gallate (EGCG) Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells. Molecules, 23.10.3390/molecules23123221 ↗
42. Green Tea Catechins Enhance the Expression of Osteoprotegerin (OPG) in Pluripotent Stem Cells
43. (−)-Epigallocatechin Gallate but Not Chlorogenic Acid Upregulates Osteoprotegerin Synthesis through Regulation of Bone Morphogenetic Protein-4 in Osteoblasts10.3892/etm.2017.4491 ↗
44. (−)-Epigallocatechin-3-Gallate (EGCG) Enhances Healing of Femoral Bone Defect10.1016/j.phymed.2018.07.012 ↗
45. Evaluation of Epigallocatechin-3-Gallate (EGCG) Modified Collagen in Guided Bone Regeneration (GBR) Surgery and Modulation of Macrophage Phenotype10.1016/j.msec.2019.01.083 ↗
46. (-)-Epigallocatechin Gallate Induces Apoptosis, via Caspase Activation, in Osteoclasts Differentiated from RAW 264.7 Cells10.1111/j.1600-0765.2006.00935.x ↗
47. Xu, H., Liu, T., Li, J., Xu, J., Chen, F., Hu, L., Zhang, B., Zi, C., Wang, X., and Sheng, J. (2019). Oxidation Derivative of (-)-Epigallocatechin-3-Gallate (EGCG) Inhibits RANKL-Induced Osteoclastogenesis by Suppressing RANK Signaling Pathways in RAW 264.7 Cells. Biomed. Pharmacother., 118.10.1016/j.biopha.2019.109237 ↗
48. Epigallocatechin-3-Gallate Increases the Formation of Mineralized Bone Nodules by Human Osteoblast-like Cells10.1016/j.jnutbio.2006.06.005 ↗
49. Inhibition of BMP-Induced Ectopic Bone Formation by an Antiangiogenic Agent (Epigallocatechin 3-Gallate)10.1080/03008200290000772 ↗
50. Epigallocatechin-3-Gallate Inhibits Osteoclastogenesis by Down-Regulating c-Fos Expression and Suppressing the Nuclear Factor-κB Signal10.1124/mol.109.057877 ↗
51. (−)-Epigallocatechin-3-gallate Suppresses Osteoclast Differentiation and Ameliorates Experimental Arthritis in Mice10.1002/art.23594 ↗
52. (−)-Epigallocatechin Gallate Inhibition of Osteoclastic Differentiation via NF-κB10.1016/j.bbrc.2009.01.007 ↗
53. Tea Polyphenols Inhibit Rat Osteoclast Formation and Differentiation10.1254/jphs.11082FP ↗
54. Epigallocatechin Gallate Suppresses Expression of Receptor Activator of NF-κB Ligand (RANKL) in Staphylococcus Aureus Infection in Osteoblast-like NRG Cells10.1099/jmm.0.47029-0 ↗
55. Effects of Tea Catechins, Epigallocatechin, Gallocatechin, and Gallocatechin Gallate, on Bone Metabolism10.1021/jf901545u ↗
56. (−)-Epigallocatechin Gallate Enhances Prostaglandin F2α-Induced VEGF Synthesis via Upregulating SAPK/JNK Activation in Osteoblasts10.1002/jcb.21104 ↗
57. (-)-Epigallocatechin Gallate Reduces Platelet-Derived Growth Factor-BB-Stimulated Interleukin-6 Synthesis in Osteoblasts: Suppression of SAPK/JNK10.1155/2008/291808 ↗
58. (−)-Epigallocatechin Gallate Suppresses Endothelin-1-Induced Interleukin-6 Synthesis in Osteoblasts: Inhibition of P44/P42 MAP Kinase Activation10.1016/j.febslet.2007.02.052 ↗
59. (-)-Epigallocatechin Gallate Inhibits Basic Fibroblast Growth Factor-Stimulated Interleukin-6 Synthesis in Osteoblasts10.1055/s-2008-1073164 ↗
60. Involvement of Caspase-3 in Epigallocatechin-3-Gallate-Mediated Apoptosis of Human Chondrosarcoma Cells10.1006/bbrc.2000.2536 ↗
61. RANKL Biology: Bone Metabolism, the Immune System, and Beyond10.1186/s41232-019-0111-3 ↗
62. Receptor Activator of Nuclear factor-κB Ligand and Osteoprotegerin10.1002/1097-0142(20010801)92:3<460::AID-CNCR1344>3.0.CO;2-D ↗
63. Genetic Regulation of Osteoclast Development and Function10.1038/nrg1122 ↗
64. Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density10.1016/S0092-8674(00)80209-3 ↗
65. Role of RANKL in Bone Diseases10.1016/j.tem.2008.10.007 ↗
66. Osteoclast Differentiation by RANKL and OPG Signaling Pathways10.1007/s00774-020-01162-6 ↗
67. Functional Dissection of Osteoprotegerin and Its Interaction with Receptor Activator of NF-kappaB Ligand10.1074/jbc.M506366200 ↗
68. Severe Osteopetrosis, Defective Interleukin-1 Signalling and Lymph Node Organogenesis in TRAF6-Deficient Mice10.1046/j.1365-2443.1999.00265.x ↗
69. Biology of RANK, RANKL, and Osteoprotegerin10.1186/ar2165 ↗
70. RANKL/OPG; Critical Role in Bone Physiology10.1007/s11154-014-9308-6 ↗
71. Resveratrol Amplifies BMP-4-Stimulated Osteoprotegerin Synthesis via P38 MAP Kinase in Osteoblasts10.3892/mmr.2015.3877 ↗
72. Alkaline Phosphatase: Structure, Expression and Its Function in Bone Mineralization10.1016/j.gene.2020.144855 ↗
73. The Role of Alkaline Phosphatase in Mineralization10.1097/BCO.0b013e3282630851 ↗
74. Alkaline Phosphatase: An Overview10.1007/s12291-013-0408-y ↗
75. Concerted Regulation of Inorganic Pyrophosphate and Osteopontin by Akp2, Enpp1, and Ank: An Integrated Model of the Pathogenesis of Mineralization Disorders10.1016/S0002-9440(10)63208-7 ↗
76. Synergism between Wnt3a and Heparin Enhances Osteogenesis via a Phosphoinositide 3-Kinase/Akt/RUNX2 Pathway10.1074/jbc.M110.122069 ↗
77. Histochemical Localization of Alkaline Phosphatase Activity in Decalcified Bone and Cartilage10.1177/002215540205000305 ↗
78. Runx2: Of Bone and Stretch10.1016/j.biocel.2007.05.024 ↗
79. Regulation of Osteoblast Differentiation by Runx2
80. Molecular Mechanism of Runx2-Dependent Bone Development
81. Roles of Runx2 in Skeletal Development10.1007/978-981-10-3233-2_6 ↗
82. Overexpression of Cbfa1 in Osteoblasts Inhibits Osteoblast Maturation and Causes Osteopenia with Multiple Fractures10.1083/jcb.200105052 ↗
83. Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation10.1016/S0092-8674(00)80257-3 ↗
84. Selective Deficiency of the “Bone-Related” Runx2-II Unexpectedly Preserves Osteoblast-Mediated Skeletogenesis10.1074/jbc.M401109200 ↗
85. Molecular Mechanisms of Osteoblast-Specific Transcription Factor Osterix Effect on Bone Formation
86. Genetic and Molecular Control of Osterix in Skeletal Formation10.1002/jcb.24439 ↗
87. Liu, Q., Li, M., Wang, S., Xiao, Z., Xiong, Y., and Wang, G. (2020). Recent Advances of Osterix Transcription Factor in Osteoblast Differentiation and Bone Formation. Front. Cell Dev. Biol., 8.10.3389/fcell.2020.601224 ↗
88. Positive Regulation of Adult Bone Formation by Osteoblast-Specific Transcription Factor Osterix10.1359/jbmr.081248 ↗
89. Phospholipase C-Β1 Interacts with Cyclin E in Adipose- Derived Stem Cells Osteogenic Differentiation10.1016/j.jbior.2018.11.001 ↗
90. Regulation of Bone Development and Extracellular Matrix Protein Genes by RUNX210.1007/s00441-009-0832-8 ↗
91. Dirzu, N., Lucaciu, O., Dirzu, D.S., Soritau, O., Cenariu, D., Crisan, B., Tefas, L., and Campian, R.S. (2022). BMP-2 Delivery through Liposomes in Bone Regeneration. Appl. Sci., 12.10.3390/app12031373 ↗
92. BMP2-Loaded Hollow Hydroxyapatite Microspheres Exhibit Enhanced Osteoinduction and Osteogenicity in Large Bone Defects10.2147/IJN.S74677 ↗
93. BMP2 Signaling in Bone Development and Repair10.1016/j.cytogfr.2009.10.018 ↗
94. Periosteal BMP2 Activity Drives Bone Graft Healing10.1016/j.bone.2012.07.017 ↗
95. Regulation of Human Cranial Osteoblast Phenotype by FGF-2, FGFR-2 and BMP-2 Signaling
96. Targeted Disruption of Cbfa1 Results in a Complete Lack of Bone Formation Owing to Maturational Arrest of Osteoblasts10.1016/S0092-8674(00)80258-5 ↗
97. Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal10.1016/j.cell.2007.09.027 ↗
98. Visualization of Cartilage Formation: Insight into Cellular Properties of Skeletal Progenitors and Chondrodysplasia Syndromes10.1016/j.devcel.2007.04.016 ↗
99. Osteoprotegerin Production by Human Osteoblast Lineage Cells Is Stimulated by Vitamin D, Bone Morphogenetic Protein-2, and Cytokines10.1006/bbrc.1998.9394 ↗
100. VEGF Couples Hypertrophic Cartilage Remodeling, Ossification and Angiogenesis during Endochondral Bone Formation10.1038/9467 ↗