Эпигаллокатехин галлат как средство борьбы с фиброзными заболеваниями

Аннотация

Эпигаллокатехин галлат зелёного чая (ЭГКГ) – полифенольное соединение, главным источником поступления которого в организм человека является зелёный чай, оказывает профилактическое и терапевтическое действие при многих заболеваниях, связанных с фиброзом тканей. Общепризнано, что фиброз тканей обусловлен отложением фибрилл коллагена во внеклеточном матриксе, что главным образом связано с нарушением функционирования клеточных сигнальных путей. Однако ранее нами было показано in vitro, что ЭГКГ может ингибировать образование коллагеновых фибриллярных структур из мономеров коллагена в экспериментах, исключающих участие клеточных сигнальных систем. В представленном обзоре мы исследуем потенциал противофиброзного действия ЭГКГ, который может осуществляться как через влияние на клеточные сигнальные системы, так и в результате непосредственного связывания ЭГКГ с мономерами коллагена, приводящего к блокированию патологического фибриллогенеза. В обзоре обсуждаются перспективы применения указанного подхода.

Сноски

* Адресат для корреспонденции.

Вклад авторов

Тараховский Ю.С. – концепция, написание текста; Гайдин С.Г. – редактирование текста статьи, участие в экспериментах, опубликованных ранее; Ким Ю.А. – руководство работой, концепция, редактирование текста статьи.

Финансирование

Исследование выполнено при поддержке Министерства науки и высшего образования Российской Федерации в рамках государственного задания ИБК РАН (075-00612-26-00) и государственного задания ИТЭБ РАН (075-00224-26-00).

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит материалов каких-либо исследований с участием людей или животных в качестве объектов.

Список литературы

1. Rana, A., Samtiya, M., Dhewa, T., Mishra, V., and Aluko, R. E. (2022) Health benefits of polyphenols: a concise review, J. Food Biochem., 46, e14264, https://doi.org/10.1111/jfbc.14264.

2. Di Lorenzo, C., Colombo, F., Biella, S., Stockley, C., and Restani, P. (2021) Polyphenols and human health: the role of bioavailability, Nutrients, 13, 273, https://doi.org/10.3390/nu13010273.

3. Shen, N., Wang, T., Gan, Q., Liu, S., Wang, L., and Jin, B. (2022) Plant flavonoids: Classification, distribution, biosynthesis, and antioxidant activity, Food Chem., 383, 132531, https://doi.org/10.1016/j.foodchem.2022.132531.

4. Al-Khayri, J. M., Sahana, G. R., Nagella, P., Joseph, B. V., Alessa, F. M., and Al-Mssallem, M. Q. (2022) Flavonoids as potential anti-inflammatory molecules: a review, Molecules, 27, 2901, https://doi.org/10.3390/molecules27092901.

5. Chagas, M. D. S. S., Behrens, M. D., Moragas-Tellis, C. J., Penedo, G. X. M., Silva, A. R., and Gonçalves-de-Albuquerque, C. F. (2022) Flavonols and flavones as potential anti-inflammatory, antioxidant, and antibacterial compounds, Oxid. Med. Cell. Longev., 2022, 9966750, https://doi.org/10.1155/2022/9966750.

6. Nicolucci, C., Padovani, M., Rodrigues, F. d. C., Fritsch, L. N., Santos, A. C., Priolli, D. G., and Sciani, J. M. (2024) Flavonoids: the use in mental health and related diseases, Nat. Prod. Res., 38, 4223-4233, https://doi.org/10.1080/14786419.2023.2275275.

7. Pyo, Y., Kwon, K. H., and Jung, Y. J. (2024) Anticancer potential of flavonoids: their role in cancer prevention and health benefits, Foods, 13, 2253, https://doi.org/10.3390/foods13142253.

8. Bouyahya, A., Balahbib, A., Khalid, A., Makeen, H. A., Alhazmi, H. A., Albratty, M., Hermansyah, A., Ming, L. C., Goh, K. W., and El Omari, N. (2024) Clinical applications and mechanism insights of natural flavonoids against type 2 diabetes mellitus, Heliyon, 10, e29718, https://doi.org/10.1016/j.heliyon.2024.e29718.

9. Stone, R. C., Chen, V., Burgess, J., Pannu, S., and Tomic-Canic, M. (2020) Genomics of human fibrotic diseases: disordered wound healing response, Int. J. Mol. Sci., 21, 8590, https://doi.org/10.3390/ijms21228590.

10. Ye, X., Li, J., Liu, Z., Sun, X., Wei, D., Song, L., and Wu, C. (2023) Peptide mediated therapy in fibrosis: Mechanisms, advances and prospects, Biomed. Pharmacother., 157, 113978, https://doi.org/10.1016/j.biopha.2022.113978.

11. Walraven, M., and Hinz, B. (2018) Therapeutic approaches to control tissue repair and fibrosis: extracellular matrix as a game changer, Matrix Biol., 71-72, 205-224, https://doi.org/10.1016/j.matbio.2018.02.020.

12. Rosenbloom, J., Macarak, E., Piera-Velazquez, S., and Jimenez, S. A. (2017) Human fibrotic diseases: current challenges in fibrosis research, Methods Mol. Biol., 1627, 1-23, https://doi.org/10.1007/978-1-4939-7113-8_1.

13. Boer, R. A. d., Keulenaer, G. d., Bauersachs, J., Brutsaert, D., Cleland, J. G., Diez, J., Du, X.-J., Ford, P., Heinzel, F. R., Lipson, K. E., McDonagh, T., Lopez-Andres, N., Lunde, I. G., Lyon, A. R., Pollesello, P., Prasad, S. K., Tocchetti, C. G., Mayr, M., Sluijter, J. P. G., Thum, T., Tschöpe, C., Zannad, F., Zimmermann, W.-H., Ruschitzka, F., Filippatos, G., Lindsey, M. L., Maack, C., and Heymans, S. (2019) Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology, Eur. J. Heart Fail., 21, 272-285, https://doi.org/10.1002/ejhf.1406.

14. Wei, W., Li, T., Chen, J., Fan, Z., Gao, F., Yu, Z., and Jiang, Y. (2024) SIRT3/6: an amazing challenge and opportunity in the fight against fibrosis and aging, Cell. Mol. Life Sci., 81, 69, https://doi.org/10.1007/s00018-023-05093-z.

15. Burke, R. M., Burgos Villar, K. N., and Small, E. M. (2021) Fibroblast contributions to ischemic cardiac remodeling, Cell. Signal., 77, 109824, https://doi.org/10.1016/j.cellsig.2020.109824.

16. Segura, A. M., Frazier, O. H., and Buja, L. M. (2014) Fibrosis and heart failure, Heart Fail. Rev., 19, 173-185, https://doi.org/10.1007/s10741-012-9365-4.

17. Mei, X., and Cheng, K. (2020) Recent development in therapeutic cardiac patches, Front. Cardiovasc. Med., 7, 610364, https://doi.org/10.3389/fcvm.2020.610364.

18. Xie, Y., van Handel, B., Qian, L., and Ardehali, R. (2023) Recent advances and future prospects in direct cardiac reprogramming, Nat. Cardiovasc. Res., 2, 1148-1158, https://doi.org/10.1038/s44161-023-00377-w.

19. Hashimoto, H., Olson, E. N., and Bassel-Duby, R. (2018) Therapeutic approaches for cardiac regeneration and repair, Nat. Rev. Cardiol., 15, 585-600, https://doi.org/10.1038/s41569-018-0036-6.

20. Yang, B., Qiao, Y., Yan, D., and Meng, Q. (2024) Targeting interactions between fibroblasts and macrophages to treat cardiac fibrosis, Cells, 13, 764, https://doi.org/10.3390/cells13090764.

21. Ravassa, S., López, B., Treibel, T. A., San José, G., Losada-Fuentenebro, B., Tapia, L., Bayés-Genís, A., Díez, J., and González, A. (2023) Cardiac fibrosis in heart failure: focus on non-invasive diagnosis and emerging therapeutic strategies, Mol. Aspects Med., 93, 101194, https://doi.org/10.1016/j.mam.2023.101194.

22. Kretschmar, C., Hernández-Cáceres, M. P., Reyes, M., Peña-Oyarzún, D., García-Navarrete, C., Troncoso, R., Díaz-Castro, F., Budini, M., Morselli, E., Riquelme, J. A., Hill, J. A., Lavandero, S., and Criollo, A. (2023) Methods for studying primary cilia in heart tissue after ischemia-reperfusion injury, Methods Cell Biol., 176, 85-101, https://doi.org/10.1016/bs.mcb.2022.12.013.

23. Zhang, Y., Ren, L., Tian, Y., Guo, X., Wei, F., and Zhang, Y. (2024) Signaling pathways that activate hepatic stellate cells during liver fibrosis, Front. Med. (Lausanne), 11, 1454980, https://doi.org/10.3389/fmed.2024.1454980.

24. Thaiss, W. M., Sannwald, L., Kloth, C., Ekert, K., Hepp, T., Boesmueller, H., Klag, T., Nikolaou, K., Horger, M., and Kaufmann, S. (2019) Quantification of hemodynamic changes in chronic liver disease: correlation of perfusion-CT data with histopathologic staging of fibrosis, Universität Ulm.

25. Barbarroja, N., Ruiz-Ponce, M., Cuesta-López, L., Pérez-Sánchez, C., López-Pedrera, C., La Arias-de Rosa, I., and Collantes-Estévez, E. (2022) Nonalcoholic fatty liver disease in inflammatory arthritis: relationship with cardiovascular risk, Front. Immunol., 13, 997270, https://doi.org/10.3389/fimmu.2022.997270.

26. Lucantoni, F., Martínez-Cerezuela, A., Gruevska, A., Moragrega, Á. B., Víctor, V. M., Esplugues, J. V., Blas-García, A., and Apostolova, N. (2021) Understanding the implication of autophagy in the activation of hepatic stellate cells in liver fibrosis: are we there yet? J. Pathol., 254, 216-228, https://doi.org/10.1002/path.5678.

27. Akkız, H., Gieseler, R. K., and Canbay, A. (2024) Liver fibrosis: from basic science towards clinical progress, focusing on the central role of hepatic stellate cells, Int. J. Mol. Sci., 25, 7873, https://doi.org/10.3390/ijms25147873.

28. Bülow, R. D., and Boor, P. (2019) Extracellular matrix in kidney fibrosis: more than just a scaffold, J. Histochem. Cytochem., 67, 643-661, https://doi.org/10.1369/0022155419849388.

29. Theocharis, A. D., Manou, D., and Karamanos, N. K. (2019) The extracellular matrix as a multitasking player in disease, FEBS J., 286, 2830-2869, https://doi.org/10.1111/febs.14818.

30. Csapo, R., Gumpenberger, M., and Wessner, B. (2020) Skeletal muscle extracellular matrix – What do we know about its composition, regulation, and physiological roles? A narrative review, Front. Physiol., 11, 253, https://doi.org/10.3389/fphys.2020.00253.

31. Onursal, C., Dick, E., Angelidis, I., Schiller, H. B., and Staab-Weijnitz, C. A. (2021) Collagen biosynthesis, processing, and maturation in lung ageing, Front. Med. (Lausanne), 8, 593874, https://doi.org/10.3389/fmed.2021.593874.

32. Luangmonkong, T., Parichatikanond, W., and Olinga, P. (2023) Targeting collagen homeostasis for the treatment of liver fibrosis: opportunities and challenges, Biochem. Pharmacol., 215, 115740, https://doi.org/10.1016/j.bcp.2023.115740.

33. Yang, L., Chen, F., Li, X., Sun, X., Li, H., Shi, H., and Zhao, G. (2026) EGCG inhibits hepatic stellate cell activity and liver fibrosis by targeting the MDM2/MUC5AC-mediated TGF-β1/Smad signaling pathway, Pathol. Res. Pract., 277, 156298, https://doi.org/10.1016/j.prp.2025.156298.

34. Yu, D.-K., Zhang, C.-X., Zhao, S.-S., Zhang, S.-H., Zhang, H., Cai, S.-Y., Shao, R.-G., and He, H.-W. (2015) The anti-fibrotic effects of epigallocatechin-3-gallate in bile duct-ligated cholestatic rats and human hepatic stellate LX-2 cells are mediated by the PI3K/Akt/Smad pathway, Acta Pharmacol. Sin., 36, 473-482, https://doi.org/10.1038/aps.2014.155.

35. Mostafa-Hedeab, G., Ewaiss Hassan, M., Halawa, T. F., and Ahmed Wani, F. (2022) Epigallocatechin gallate ameliorates tetrahydrochloride-induced liver toxicity in rats via inhibition of TGFβ/p-ERK/p-Smad1/2 signaling, antioxidant, anti-inflammatory activity, Saudi Pharm. J., 30, 1293-1300, https://doi.org/10.1016/j.jsps.2022.06.021.

36. Burgy, O., and Königshoff, M. (2024) Teatime: epigallocatechin gallate targets fibroblast-epithelial cell crosstalk to combat lung fibrosis, J. Clin. Invest., 134, e183970, https://doi.org/10.1172/JCI183970.

37. Cohen, M. L., Brumwell, A. N., Ho, T. C., Garakani, K., Montas, G., Leong, D., Ding, V. W., Golden, J. A., Trinh, B. N., Jablons, D. M., Matthay, M. A., Jones, K. D., Wolters, P. J., Wei, Y., Chapman, H. A., and Le Saux, C. J. (2024) A fibroblast-dependent TGF-β1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis, J. Clin. Invest., 134, e174598, https://doi.org/10.1172/JCI174598.

38. Adamcakova, J., Balentova, S., Barosova, R., Hanusrichterova, J., Mikolka, P., Prso, K., Mokry, J., Tatarkova, Z., Kalenska, D., and Mokra, D. (2023) Effects of green tea polyphenol epigallocatechin-3-gallate on markers of inflammation and fibrosis in a rat model of pulmonary silicosis, Int. J. Mol. Sci., 24, 1857, https://doi.org/10.3390/ijms24031857.

39. Mohan, T., Velusamy, P., Chakrapani, L. N., Srinivasan, A. K., Singh, A., Johnson, T., and Periandavan, K. (2017) Impact of EGCG supplementation on the progression of diabetic nephropathy in rats: an insight into fibrosis and apoptosis, J. Agric. Food Chem., 65, 8028-8036, https://doi.org/10.1021/acs.jafc.7b03301.

40. Li, G., Yang, H., Zhang, D., Zhang, Y., Liu, B., Wang, Y., Zhou, H., Xu, Z.-X., and Wang, Y. (2024) The role of macrophages in fibrosis of chronic kidney disease, Biomed. Pharmacother., 177, 117079, https://doi.org/10.1016/j.biopha.2024.117079.

41. Li, F., Zhou, Y., Liu, B., Du, Z., and Huang, W. (2025) Epigallocatechin gallate-mediated inhibition of mitochondrial DNA sensing regulated by TBK1/cGAS/STING and NLRP3 alleviates cardiovascular toxicity in atherosclerosis, Int. Immunopharmacol., 164, 115375, https://doi.org/10.1016/j.intimp.2025.115375.

42. Wang, L., Li, L., Zhao, D., Yuan, H., Zhang, H., Chen, J., Pang, D., Lu, Y., and Ouyang, H. (2024) MYH7 R453C induced cardiac remodelling via activating TGF-β/Smad2/3, ERK1/2 and Nox4/ROS/NF-κB signalling pathways, Open Biol., 14, 230427, https://doi.org/10.1098/rsob.230427.

43. Li, T., Tong, Q., Wang, Z., Yang, Z., Sun, Y., Cai, J., Xu, Q., Lu, Y., Liu, X., Lin, K., and Qian, Y. (2024) Epigallocatechin-3-gallate inhibits atrial fibrosis and reduces the occurrence and maintenance of atrial fibrillation and its possible mechanisms, Cardiovasc. Drugs Ther., 38, 895-916, https://doi.org/10.1007/s10557-023-07447-y.

44. Jia, Q., Yang, R., Mehmood, S., and Li, Y. (2022) Epigallocatechin-3-gallate attenuates myocardial fibrosis in diabetic rats by activating autophagy, Exp. Biol. Med. (Maywood), 247, 1591-1600, https://doi.org/10.1177/15353702221110646.

45. Gui, L., Wang, F., Hu, X., Liu, X., Yang, H., Cai, Z., Qi, M., and Dai, C. (2022) Epigallocatechin gallate protects diabetes mellitus rats complicated with cardiomyopathy through TGF-β1/JNK signaling pathway, Curr. Pharm. Des., 28, 2758-2770, https://doi.org/10.2174/1381612828666220902115437.

46. Ren, L. L., Li, X. J., Duan, T. T., Li, Z. H., Yang, J. Z., Zhang, Y. M., Zou, L., Miao, H., and Zhao, Y. Y. (2023) Transforming growth factor-β signaling: from tissue fibrosis to therapeutic opportunities, Chem. Biol. Interact., 369, 110289, https://doi.org/10.1016/j.cbi.2022.110289.

47. He, C., Wang, D., Wang, R., Huang, Y., Huang, X., Shen, S., Lv, J., and Wu, M. (2022) Epigallocatechin gallate induces the demethylation of actinin alpha 4 to inhibit diabetic nephropathy renal fibrosis via the NF-κB signaling pathway in vitro, Dose Response, 20, 15593258221105704, https://doi.org/10.1177/15593258221105704.

48. Zhang, Y., Li, J., Wang, Z., Chen, J., Zhao, M., Guo, C., Wang, T., Li, R., Zhang, H., Ma, X., Wen, Y., Zeng, J., and Efferth, T. (2025) Preclinical evidence construction for epigallocatechin-3-gallate against non-alcoholic fatty liver disease: a meta-analysis and machine learning study, Phytomedicine, 142, 156651, https://doi.org/10.1016/j.phymed.2025.156651.

49. Li, D., Cao, D., Sun, Y., Cui, Y., Zhang, Y., Jiang, J., and Cao, X. (2024) The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy, Front. Immunol., 15, 1331641, https://doi.org/10.3389/fimmu.2024.1331641.

50. Neuzil, J., Wang, X.-F., Dong, L.-F., Low, P., and Ralph, S. J. (2006) Molecular mechanism of ‘mitocan’-induced apoptosis in cancer cells epitomizes the multiple roles of reactive oxygen species and Bcl-2 family proteins, FEBS Lett., 580, 5125-5129, https://doi.org/10.1016/j.febslet.2006.05.072.

51. Vostrikova, S. M., Grinev, A. B., and Gogvadze, V. G. (2020) Reactive oxygen species and antioxidants in carcinogenesis and tumor therapy, Biochemistry (Moscow), 85, 1254-1266, https://doi.org/10.1134/S0006297920100132.

52. Meng, Q., Velalar, C. N., and Ruan, R. (2008) Effects of epigallocatechin-3-gallate on mitochondrial integrity and antioxidative enzyme activity in the aging process of human fibroblast, Free Radic. Biol. Med., 44, 1032-1041, https://doi.org/10.1016/j.freeradbiomed.2007.11.023.

53. Lambert, J. D., and Elias, R. J. (2010) The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention, Arch. Biochem. Biophys., 501, 65-72, https://doi.org/10.1016/j.abb.2010.06.013.

54. Kanadzu, M., Lu, Y., and Morimoto, K. (2006) Dual function of (–)-epigallocatechin gallate (EGCG) in healthy human lymphocytes, Cancer Lett., 241, 250-255, https://doi.org/10.1016/j.canlet.2005.10.021.

55. Collins, Q. F., Liu, H.-Y., Pi, J., Liu, Z., Quon, M. J., and Cao, W. (2007) Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, suppresses hepatic gluconeogenesis through 5′-AMP-activated protein kinase, J. Biol. Chem., 282, 30143-30149, https://doi.org/10.1074/jbc.M702390200.

56. Helvacıoğlu, S., Hamitoğlu, M., Yıldırım, E., Vural Korkut, Ş., Yaba, A., and Aydın, A. (2025) Protective effects of rosmarinic acid and epigallocatechin gallate against doxorubicin-induced cytotoxicity and genotoxicity in CHO-K1 cells, Turk. J. Pharm. Sci., 21, 536-543, https://doi.org/10.4274/tjps.galenos.2024.80552.

57. Hazimeh, D., Massoud, G., Parish, M., Singh, B., Segars, J., and Islam, M. S. (2023) Green tea and benign gynecologic disorders: a new trick for an old beverage? Nutrients, 15, 1439, https://doi.org/10.3390/nu15061439.

58. Yang, L., Jia, L., Li, X., Zhang, K., Wang, X., He, Y., Hao, M., Rayman, M. P., and Zhang, J. (2022) Prooxidant activity-based guideline for a beneficial combination of (–)-epigallocatechin-3-gallate and chlorogenic acid, Food Chem., 386, 132812, https://doi.org/10.1016/j.foodchem.2022.132812.

59. Vladu, A. F., Ficai, D., Ene, A. G., and Ficai, A. (2022) Combination therapy using polyphenols: An efficient way to improve antitumor activity and reduce resistance, Int. J. Mol. Sci., 23, 10244, https://doi.org/10.3390/ijms231810244.

60. Lee, Y., Lee, J., and Lim, C. (2021) Anticancer activity of flavonoids accompanied by redox state modulation and the potential for a chemotherapeutic strategy, Food Sci. Biotechnol., 30, 321-340, https://doi.org/10.1007/s10068-021-00899-8.

61. Nakagawa, H., Hasumi, K., Woo, J.-T., Nagai, K., and Wachi, M. (2004) Generation of hydrogen peroxide primarily contributes to the induction of Fe(II)-dependent apoptosis in Jurkat cells by (–)-epigallocatechin gallate, Carcinogenesis, 25, 1567-1574, https://doi.org/10.1093/carcin/bgh168.

62. Chen, S., Xiong, Y., Yang, F., Hu, Y., Feng, J., Zhou, F., Liu, Z., Liu, H., Liu, X., Zhao, J., Zhang, Z., and Chen, L. (2024) Approaches to scarless burn wound healing: application of 3D printed skin substitutes with dual properties of anti-infection and balancing wound hydration levels, EBioMedicine, 106, 105258, https://doi.org/10.1016/j.ebiom.2024.105258.

63. Hu, Y., Xiong, Y., Zhu, Y., Zhou, F., Liu, X., Chen, S., Li, Z., Qi, S., and Chen, L. (2023) Copper-epigallocatechin gallate enhances therapeutic effects of 3D-printed dermal scaffolds in mitigating diabetic wound scarring, ACS Appl. Mater. Interfaces, 15, 38230-38246, https://doi.org/10.1021/acsami.3c04733.

64. Farhan, M., Khan, H. Y., Oves, M., Al-Harrasi, A., Rehmani, N., Arif, H., Hadi, S. M., and Ahmad, A. (2016) Cancer therapy by catechins involves redox cycling of copper ions and generation of reactive oxygen species, Toxins (Basel), 8, 37, https://doi.org/10.3390/toxins8020037.

65. Chen, Z., Duan, J., Diao, Y., Chen, Y., Liang, X., Li, H., Miao, Y., Gao, Q., Gui, L., Wang, X., Yang, J., and Li, Y. (2021) ROS-responsive capsules engineered from EGCG-zinc networks improve therapeutic angiogenesis in mouse limb ischemia, Bioact. Mater., 6, 1-11, https://doi.org/10.1016/j.bioactmat.2020.07.013.

66. Tang, C., Wang, H., Guo, L., Cui, Y., Zou, C., Hu, J., Zhang, H., Yang, G., and Zhou, W. (2025) Multifunctional nanomedicine for targeted atherosclerosis therapy: activating plaque clearance cascade and suppressing inflammation, ACS Nano, 19, 3339-3361, https://doi.org/10.1021/acsnano.4c12131.

67. Wang, J., Zhang, R., Xie, H., Yang, Y., Chen, H., and Lin, Q. (2025) Metal-phenolic epigallocatechin gallate-zinc antioxidant nanoparticles for cataract treatment, J. Control. Release, 383, 113798, https://doi.org/10.1016/j.jconrel.2025.113798.

68. Wei, H., Qin, J., Huang, Q., Jin, Z., Zheng, L., Zhao, J., and Qin, Z. (2023) Epigallocatechin-3-gallate (EGCG) based metal-polyphenol nanoformulations alleviates chondrocytes inflammation by modulating synovial macrophages polarization, Biomed. Pharmacother., 161, 114366, https://doi.org/10.1016/j.biopha.2023.114366.

69. Wang, Z., Shi, R., Niu, M., Liu, Y., Tang, C., Li, S., Lv, Y., Liu, Z., and Zhao, X. (2025) A metal-phenolic functionalized bacterial cellulose hydrogel: a novel strategy for near infrared triggered multistage regulation of infected wound healing, Int. J. Biol. Macromol., 331, 148452, https://doi.org/10.1016/j.ijbiomac.2025.148452.

70. Ouyang, J., Zhu, K., Liu, Z., and Huang, J. (2020) Prooxidant effects of epigallocatechin-3-gallate in health benefits and potential adverse effect, Oxid. Med. Cell. Longev., 2020, 9723686, https://doi.org/10.1155/2020/9723686.

71. Martin, K. R., and Barrett, J. C. (2002) Reactive oxygen species as double-edged swords in cellular processes: Low-dose cell signaling versus high-dose toxicity, Hum. Exp. Toxicol., 21, 71-75, https://doi.org/10.1191/0960327102ht213oa.

72. Seifried, H. E., Anderson, D. E., Fisher, E. I., and Milner, J. A. (2007) A review of the interaction among dietary antioxidants and reactive oxygen species, J. Nutr. Biochem., 18, 567-579, https://doi.org/10.1016/j.jnutbio.2006.10.007.

73. Raza, M. H., Siraj, S., Arshad, A., Waheed, U., Aldakheel, F., Alduraywish, S., and Arshad, M. (2017) ROS-modulated therapeutic approaches in cancer treatment, J. Cancer Res. Clin. Oncol., 143, 1789-1809, https://doi.org/10.1007/s00432-017-2464-9.

74. Fernández-Iglesias, A., Quesada, H., Díaz, S., Pajuelo, D., Bladé, C., Arola, L., Josepa Salvadó, M., and Mulero, M. (2013) DHA sensitizes FaO cells to tert-BHP-induced oxidative effects. Protective role of EGCG, Food Chem. Toxicol., 62, 750-757, https://doi.org/10.1016/j.fct.2013.10.013.

75. Kumar, A., and Bora, U. (2013) Interactions of curcumin and its derivatives with nucleic acids and their implications, Mini Rev. Med. Chem., 13, 256-264, https://doi.org/10.2174/1389557511313020007.

76. Salehi, B., Mishra, A. P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., Fokou, P. V. T., Martins, N., and Sharifi-Rad, J. (2018) Resveratrol: a double-edged sword in health benefits, Biomedicines, 6, 91, https://doi.org/10.3390/biomedicines6030091.

77. Siadat, S. M., and Ruberti, J. W. (2023) Mechanochemistry of collagen, Acta Biomater., 163, 50-62, https://doi.org/10.1016/j.actbio.2023.01.025.

78. Wohlgemuth, R. P., Brashear, S. E., and Smith, L. R. (2023) Alignment, cross linking, and beyond: a collagen architect’s guide to the skeletal muscle extracellular matrix, Am. J. Physiol. Cell Physiol., 325, C1017-C1030, https://doi.org/10.1152/ajpcell.00287.2023.

79. Tarahovsky, Y. S., Gaidin, S. G., and Kim, Y. A. (2024) Effects of catechins on the formation of collagen fibrils in vitro [in Russian], Biofizika, 69, 707-714, https://doi.org/10.31857/S0006302924040038.

80. Kim, Y. A., Tarahovsky, Y. S., Gaidin, S. G., Yagolnik, E. A., and Muzafarov, E. N. (2017) Flavonoids determine the rate of fibrillogenesis and structure of collagen type I fibrils in vitro, Int. J. Biol. Macromol., 104, 631-637, https://doi.org/10.1016/j.ijbiomac.2017.06.070.

81. Tarahovsky, Y. S., Selezneva, I. I., Vasilieva, N. A., Egorochkin, M. A., and Kim, Y. A. (2007) Acceleration of fibril formation and thermal stabilization of collagen fibrils in the presence of taxifolin (dihydroquercetin), Bull. Exp. Biol. Med., 144, 791-794, https://doi.org/10.1007/s10517-007-0433-z.

82. Williams, B. R., Gelman, R. A., Poppke, D. C., and Piez, K. A. (1978) Collagen fibril formation. Optimal in vitro conditions and preliminary kinetic results, J. Biol. Chem., 253, 6578-6585, https://doi.org/10.1016/S0021-9258(19)46970-6.

83. Ferrer, E. G., Salinas, M. V., Correa, M. J., Naso, L., Barrio, D. A., Etcheverry, S. B., Lezama, L., Rojo, T., and Williams, P. A. M. (2006) Synthesis, characterization, antitumoral and osteogenic activities of quercetin vanadyl(IV) complexes, J. Biol. Inorg. Chem., 11, 791-801, https://doi.org/10.1007/s00775-006-0122-9.

84. Bozec, L., van der Heijden, G., and Horton, M. (2007) Collagen fibrils: Nanoscale ropes, Biophys. J., 92, 70-75, https://doi.org/10.1529/biophysj.106.085704.

85. Dey, P., Olmstead, B. D., Sasaki, G. Y., Vodovotz, Y., Yu, Z., and Bruno, R. S. (2020) Epigallocatechin gallate but not catechin prevents nonalcoholic steatohepatitis in mice similar to green tea extract while differentially affecting the gut microbiota, J. Nutr. Biochem., 84, 108455, https://doi.org/10.1016/j.jnutbio.2020.108455.

86. Kim, Y. A., Gaidin, S. G., and Tarahovsky, Y. S. (2018) The influence of simple phenols on collagen type I fibrillogenesis in vitro, Biophysics, 63, 162-168, https://doi.org/10.1134/S0006350918020148.

87. Song, Y., Wang, T., Yang, L., Wu, J., Chen, L., Fan, X., Zhang, Z., Yang, Q., Yu, Z., and Song, B. (2023) EGCG inhibits hypertrophic scar formation in a rabbit ear model, J. Cosmet. Dermatol., 22, 1382-1391, https://doi.org/10.1111/jocd.15587.

88. Fan, Z., Xia, G., Zhu, F., Yang, N., Ma, A., Shi, Y., Jiang, Z., Zhou, X., and Hou, Z. (2025) Ruthenium-quercetin coordinated nanotherapeutics with macrophage polarization regulation to rapidly promote bacterial-infected wound healing, Mater. Today Bio, 33, 101983, https://doi.org/10.1016/j.mtbio.2025.101983.

89. McKay, T. B., Emmitte, K. A., German, C., and Karamichos, D. (2023) Quercetin and related analogs as therapeutics to promote tissue repair, Bioengineering (Basel), 10, 1127, https://doi.org/10.3390/bioengineering10101127.

90. Zhang, N., Yan, C., Yin, C., Hu, X., Guan, P., and Cheng, Y. (2022) Structural remodeling mechanism of the toxic amyloid fibrillary mediated by epigallocatechin-3-gallate, ACS Omega, 7, 48047-48058, https://doi.org/10.1021/acsomega.2c05995.

91. Li, X., Zhang, Y., Wang, Y., Zhang, S., and Zhang, L. (2024) Molecular insights into the inhibition and disaggregation effects of EGCG on Aβ40 and Aβ42 cofibrillation, J. Phys. Chem. B, 128, 1843-1853, https://doi.org/10.1021/acs.jpcb.3c07232.

92. Ziaunys, M., Mikalauskaite, K., Sakalauskas, A., and Smirnovas, V. (2021) Interplay between epigallocatechin-3-gallate and ionic strength during amyloid aggregation, PeerJ, 9, e12381, https://doi.org/10.7717/peerj.12381.

93. Fernandes, L., Cardim-Pires, T. R., Foguel, D., and Palhano, F. L. (2021) Green tea polyphenol epigallocatechin-gallate in amyloid aggregation and neurodegenerative diseases, Front. Neurosci., 15, 718188, https://doi.org/10.3389/fnins.2021.718188.

94. Srivastava, A., Al Adem, K., Shanti, A., Lee, S., Abedrabbo, S., and Homouz, D. (2024) Inhibition of the early-stage cross-amyloid aggregation of amyloid-β and IAPP via EGCG: Insights from molecular dynamics simulations, ACS Omega, 9, 30256-30269, https://doi.org/10.1021/acsomega.4c00500.

95. Al Adem, K., Shanti, A., Srivastava, A., Homouz, D., Thomas, S. A., Khair, M., Stefanini, C., Chan, V., Kim, T.-Y., and Lee, S. (2022) Linking Alzheimer’s disease and type 2 diabetes: characterization and inhibition of cytotoxic Aβ and IAPP hetero-aggregates, Front. Mol. Biosci., 9, 842582, https://doi.org/10.3390/fmolb.2022.842582.

96. Bieschke, J., Russ, J., Friedrich, R. P., Ehrnhoefer, D. E., Wobst, H., Neugebauer, K., and Wanker, E. E. (2010) EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity, Proc. Natl. Acad. Sci. USA, 107, 7710-7715, https://doi.org/10.1073/pnas.0910723107.

97. Sonawane, S. K., Chidambaram, H., Boral, D., Gorantla, N. V., Balmik, A. A., Dangi, A., Ramasamy, S., Marelli, U. K., and Chinnathambi, S. (2020) EGCG impedes human Tau aggregation and interacts with Tau, Sci. Rep., 10, 12579, https://doi.org/10.1038/s41598-020-69429-6.

98. Valverde-Salazar, V., Ruiz-Gabarre, D., and García-Escudero, V. (2023) Alzheimer’s disease and green tea: epigallocatechin-3-gallate as a modulator of inflammation and oxidative stress, Antioxidants (Basel), 12, 1460, https://doi.org/10.3390/antiox12071460.

99. Jena, A. B., Dash, U. C., and Duttaroy, A. K. (2022) An in silico investigation on the interactions of curcumin and epigallocatechin-3-gallate with NLRP3 inflammasome complex, Biomed. Pharmacother., 156, 113890, https://doi.org/10.1016/j.biopha.2022.113890.

100. Fan, Q., Zhou, X.-H., Wang, T.-F., Zeng, F.-J., Liu, X., Gu, Y., Chen, B., Yang, J., Pang, Z.-Y., Liu, J.-G., and Bai, G.-H. (2023) Effects of epigallocatechin-3-gallate on oxidative stress, inflammation, and bone loss in a rat periodontitis model, J. Dent. Sci., 18, 1567-1575, https://doi.org/10.1016/j.jds.2023.02.019.

101. Yasuda, Y., Shimizu, M., Sakai, H., Iwasa, J., Kubota, M., Adachi, S., Osawa, Y., Tsurumi, H., Hara, Y., and Moriwaki, H. (2009) (–)-Epigallocatechin gallate prevents carbon tetrachloride-induced rat hepatic fibrosis by inhibiting the expression of the PDGFRβ and IGF-1R, Chem. Biol. Interact., 182, 159-164, https://doi.org/10.1016/j.cbi.2009.07.015.

102. Wei, Y., Dong, W., Jackson, J., Ho, T.-C., Le Saux, C. J., Brumwell, A., Li, X., Klesney-Tait, J., Cohen, M. L., Wolters, P. J., and Chapman, H. A. (2021) Blocking LOXL2 and TGFβ1 signalling induces collagen I turnover in precision-cut lung slices derived from patients with idiopathic pulmonary fibrosis, Thorax, 76, 729-732, https://doi.org/10.1136/thoraxjnl-2020-215745.

103. Pan, M., Li, H., and Shi, X. (2024) A new target for hepatic fibrosis prevention and treatment: the Warburg effect, Front. Biosci. (Landmark Ed), 29, 321, https://doi.org/10.31083/j.fbl2909321.

104. Li, Y., Zhu, M., Huo, Y., Zhang, X., and Liao, M. (2018) Anti-fibrosis activity of combination therapy with epigallocatechin gallate, taurine and genistein by regulating glycolysis, gluconeogenesis, and ribosomal and lysosomal signaling pathways in HSC-T6 cells, Exp. Ther. Med., 16, 4329-4338, https://doi.org/10.3892/etm.2018.6743.

105. Won, H.-R., Lee, P., Oh, S.-R., and Kim, Y.-M. (2021) Epigallocatechin-3-gallate suppresses the expression of TNF-α-induced MMP-1 via MAPK/ERK signaling pathways in human dermal fibroblasts, Biol. Pharm. Bull., 44, 18-24, https://doi.org/10.1248/bpb.b20-00304.

106. Huang, Y., Liu, R., Meng, T., Zhang, B., Ma, J., and Liu, X. (2024) The TGFβ1/SMADs/Snail1 signaling axis mediates pericyte-derived fibrous scar formation after spinal cord injury, Int. Immunopharmacol., 128, 111482, https://doi.org/10.1016/j.intimp.2023.111482.

107. Park, G., Yoon, B. S., Moon, J.-H., Kim, B., Jun, E. K., Oh, S., Kim, H., Song, H. J., Noh, J. Y., Oh, C., and You, S. (2008) Green tea polyphenol epigallocatechin-3-gallate suppresses collagen production and proliferation in keloid fibroblasts via inhibition of the STAT3-signaling pathway, J. Invest. Dermatol., 128, 2429-2441, https://doi.org/10.1038/jid.2008.103.

108. Lam, W. H., Kazi, A., Kuhn, D. J., Chow, L. M. C., Chan, A. S. C., Dou, Q. P., and Chan, T. H. (2004) A potential prodrug for a green tea polyphenol proteasome inhibitor: Evaluation of the peracetate ester of (–)-epigallocatechin gallate (–)-EGCG, Bioorg. Med. Chem., 12, 5587-5593, https://doi.org/10.1016/j.bmc.2004.08.002.

109. Reddy, V. C., Vidya, S. G. V., Sreeramulu, D., Venu, L., and Raghunath, M. (2005) Addition of milk does not alter the antioxidant activity of black tea, Ann. Nutr. Metab., 49, 189-195, https://doi.org/10.1159/000087071.

110. Van Amelsvoort, J. M., van Hof, K. H., Mathot, J. N., Mulder, T. P., Wiersma, A., and Tijburg, L. B. (2001) Plasma concentrations of individual tea catechins after a single oral dose in humans, Xenobiotica, 31, 891-901, https://doi.org/10.1080/00498250110079149.

111. Yang, C. S., Chen, L., Lee, M. J., Balentine, D., Kuo, M. C., and Schantz, S. P. (1998) Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers, Cancer Epidemiol. Biomarkers Prev., 7, 351-354.

112. Lee, M.-J., Maliakal, P., Chen, L., Meng, X., Bondoc, F. Y., Prabhu, S., Lambert, G., Mohr, S., and Yang, C. S. (2002) Pharmacokinetics of tea catechins after ingestion of green tea and (−)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability, Cancer Epidemiol. Biomarkers Prev., 11, 1025-1032.

113. Janle, E. M., Morré, D. M., Morré, D. J., Zhou, Q., and Zhu, Y. (2008) Pharmacokinetics of green tea catechins in extract and sustained-release preparations, J. Diet. Suppl., 5, 248-263, https://doi.org/10.1080/19390210802414279.

114. Chow, H. H., Cai, Y., Alberts, D. S., Hakim, I., Dorr, R., Shahi, F., Crowell, J. A., Yang, C. S., and Hara, Y. (2001) Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E, Cancer Epidemiol. Biomarkers Prev., 10, 53-58.

115. Clifford, M. N., van der Hooft, J. J. J., and Crozier, A. (2013) Human studies on the absorption, distribution, metabolism, and excretion of tea polyphenols, Am. J. Clin. Nutr., 98, 1619S-1630S, https://doi.org/10.3945/ajcn.113.058958.

116. Rovaldi, E., Di Donato, V., Paolino, G., Bruno, M., Medei, A., Nisticò, S. P., Pellacani, G., Kiss, N., Azzella, G., Banvolgyi, A., and Cantisani, C. (2025) Epigallocatechin-gallate (EGCG): An essential molecule for human health and well-being, Int. J. Mol. Sci., 26, 9253, https://doi.org/10.3390/ijms26189253.

117. Chow, H.-H. S., Cai, Y., Hakim, I. A., Crowell, J. A., Shahi, F., Brooks, C. A., Dorr, R. T., Hara, Y., and Alberts, D. S. (2003) Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals, Clin. Cancer Res., 9, 3312-3319.

118. Chow, H. H., Hakim, I. A., Vining, D. J., Crowell, J. A., Ranger-Moore, J., Chew, W. M., Celaya, C. A., Rodney, S. R., Hara, Y., and Alberts, D. S. (2005) Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals, Clin. Cancer Res., 11, 4627-4633, https://doi.org/10.1158/1078-0432.CCR-04-2549.

119. Isbrucker, R. A., Edwards, J. A., Wolz, E., Davidovich, A., and Bausch, J. (2006) Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: Dermal, acute and short-term toxicity studies, Food Chem. Toxicol., 44, 636-650, https://doi.org/10.1016/j.fct.2005.11.003.

120. Lorenz, M. (2013) Cellular targets for the beneficial actions of tea polyphenols, Am. J. Clin. Nutr., 98, 1642S-1650S, https://doi.org/10.3945/ajcn.113.058230.

121. Uekusa, Y., Kamihira-Ishijima, M., Sugimoto, O., Ishii, T., Kumazawa, S., Nakamura, K., Tanji, K.-i., Naito, A., and Nakayama, T. (2011) Interaction of epicatechin gallate with phospholipid membranes as revealed by solid-state NMR spectroscopy, Biochim. Biophys. Acta, 1808, 1654-1660, https://doi.org/10.1016/j.bbamem.2011.02.014.

122. Tarahovsky, Y. S. (2022) Hitchhiking into a cell: flavonoids may produce complexes with transition metals for transmembrane translocation, Biometals, 35, 1299-1306, https://doi.org/10.1007/s10534-022-00445-x.

123. Kim, Y. A., Tarahovsky, Y. S., Yagolnik, E. A., Kuznetsova, S. M., and Muzafarov, E. N. (2015) Integration of quercetin-iron complexes into phosphatidylcholine or phosphatidylethanolamine liposomes, Appl. Biochem. Biotechnol., 176, 1904-1913, https://doi.org/10.1007/s12010-015-1686-z.

124. Kim, Y. A., Tarahovsky, Y. S., Yagolnik, E. A., Kuznetsova, S. M., and Muzafarov, E. N. (2013) Lipophilicity of flavonoid complexes with iron(II) and their interaction with liposomes, Biochem. Biophys. Res. Commun., 431, 680-685, https://doi.org/10.1016/j.bbrc.2013.01.060.

125. Han, D. W., Matsumura, K., Kim, B., and Hyon, S. H. (2008) Time-dependent intracellular trafficking of FITC-conjugated epigallocatechin-3-O-gallate in L-929 cells, Bioorg. Med. Chem., 16, 9652-9659, https://doi.org/10.1016/j.bmc.2008.10.009.

126. Kuzuhara, T., Tanabe, A., Sei, Y., Yamaguchi, K., Suganuma, M., and Fujiki, H. (2007) Synergistic effects of multiple treatments, and both DNA and RNA direct bindings on, green tea catechins, Mol. Carcinog., 46, 640-645, https://doi.org/10.1002/mc.20332.

127. Kuzuhara, T., Sei, Y., Yamaguchi, K., Suganuma, M., and Fujiki, H. (2006) DNA and RNA as new binding targets of green tea catechins, J. Biol. Chem., 281, 17446-17456, https://doi.org/10.1074/jbc.M601196200.

128. Tarahovsky, Y. S., Kim, Y. A., Yagolnik, E. A., and Muzafarov, E. N. (2014) Flavonoid-membrane interactions: involvement of flavonoid-metal complexes in raft signaling, Biochim. Biophys. Acta, 1838, 1235-1246, https://doi.org/10.1016/j.bbamem.2014.01.021.

129. Tarahovsky, Y. S., Muzafarov, E. N., and Kim, Y. A. (2008) Rafts making and rafts braking: How plant flavonoids may control membrane heterogeneity, Mol. Cell. Biochem., 314, 65-71, https://doi.org/10.1007/s11010-008-9766-9.

130. Patra, S. K., Rizzi, F., Silva, A., Rugina, D. O., and Bettuzzi, S. (2008) Molecular targets of (–)-epigallocatechin-3-gallate (EGCG): specificity and interaction with membrane lipid rafts, J. Physiol. Pharmacol., 59, 217-235.

131. Zhu, W., Deng, X., Peng, J., Zou, B., and Li, C. (2017) A-type ECG and EGCG dimers inhibit 3T3-L1 differentiation by binding to cholesterol in lipid rafts, J. Nutr. Biochem., 48, 62-73, https://doi.org/10.1016/j.jnutbio.2017.06.012.

132. Koonyosying, P., Tharanon, W., Pairojthanachai, K., Samakarn, Y., Meejak, K., Paradee, N., Kerdto, O., Yubo, S., et al. (2025) Green tea catechins mitigate hepatocyte ferroptosis through attenuation of oxidative stress and improvement of antioxidant systems, Antioxidants (Basel), 14, 1483, https://doi.org/10.3390/antiox14121483.

133. Prananda, A. T., Nugraha, S. E., Situmorang, P. C., and Syahputra, R. A. (2025) Comparative effectiveness of plant-derived compounds in keloid management: a review, Front. Pharmacol., 16, 1576851, https://doi.org/10.3389/fphar.2025.1576851.

134. Li, W., Mei, X., and Tu, Y. Y. (2012) Effects of tea polyphenols and their polymers on MAPK signaling pathways in cancer research, Mini Rev. Med. Chem., 12, 120-126, https://doi.org/10.2174/138955712798995011.

135. Van Aller, G. S., Carson, J. D., Tang, W., Peng, H., Zhao, L., Copeland, R. A., Tummino, P. J., and Luo, L. (2011) Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor, Biochem. Biophys. Res. Commun., 406, 194-199, https://doi.org/10.1016/j.bbrc.2011.02.010.

136. Halder, B., Das Gupta, S., and Gomes, A. (2012) Black tea polyphenols induce human leukemic cell cycle arrest by inhibiting Akt signaling: possible involvement of Hsp90, Wnt/β-catenin signaling and FOXO1, FEBS J., 279, 2876-2891, https://doi.org/10.1111/j.1742-4658.2012.08668.x.

137. Lee, M. H., Han, D.-W., Hyon, S.-H., and Park, J.-C. (2011) Apoptosis of human fibrosarcoma HT-1080 cells by epigallocatechin-3-O-gallate via induction of p53 and caspases as well as suppression of Bcl-2 and phosphorylated nuclear factor-κB, Apoptosis, 16, 75-85, https://doi.org/10.1007/s10495-010-0548-y.

138. Pullikotil, P., Chen, H., Muniyappa, R., Greenberg, C. C., Yang, S., Reiter, C. E. N., Lee, J.-W., Chung, J. H., and Quon, M. J. (2012) Epigallocatechin gallate induces expression of heme oxygenase-1 in endothelial cells via p38 MAPK and Nrf-2 that suppresses proinflammatory actions of TNF-α, J. Nutr. Biochem., 23, 1134-1145, https://doi.org/10.1016/j.jnutbio.2011.06.007.

139. Lorenz, M., Wessler, S., Follmann, E., Michaelis, W., Düsterhöft, T., Baumann, G., Stangl, K., and Stangl, V. (2004) A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation, J. Biol. Chem., 279, 6190-6195, https://doi.org/10.1074/jbc.M309114200.

140. Ohishi, T., Hayakawa, S., and Miyoshi, N. (2023) Involvement of microRNA modifications in anticancer effects of major polyphenols from green tea, coffee, wine, and curry, Crit. Rev. Food Sci. Nutr., 63, 7148-7179, https://doi.org/10.1080/10408398.2022.2038540.

141. Nagle, D. G., Ferreira, D., and Zhou, Y.-D. (2006) Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives, Phytochemistry, 67, 1849-1855, https://doi.org/10.1016/j.phytochem.2006.06.020.

142. Tong, M.-Q., Lu, C.-T., Huang, L.-T., Yang, J.-J., Yang, S.-T., Chen, H.-B., Xue, P.-P., Luo, L.-Z., Yao, Q., Xu, H.-L., and Zhao, Y.-Z. (2023) Polyphenol-driven facile assembly of a nanosized acid fibroblast growth factor-containing coacervate accelerates the healing of diabetic wounds, Acta Biomater., 157, 467-486, https://doi.org/10.1016/j.actbio.2022.11.054.

143. Cao, X., Deng, Y., Xu, Z., Wang, T., Tang, B., Han, J., Guo, R., and Yin, R. (2024) A versatile natural gelatin-based hydrogel for emergency wound treatment through hemostasis, antibacterial, and anti-inflammation, Biofabrication, 17, 015017, https://doi.org/10.1088/1758-5090/ad89ff.

144. Xu, F.-W., Lv, Y.-L., Zhong, Y.-F., Xue, Y.-N., Wang, Y., Zhang, L.-Y., Hu, X., and Tan, W.-Q. (2021) Beneficial effects of green tea EGCG on skin wound healing: a comprehensive review, Molecules, 26, 6123, https://doi.org/10.3390/molecules26206123.

145. He, X., Gao, Y., Wang, X., Zhang, C., Xia, Z., Xu, W., Yang, H., Tao, G., Cai, R., Chen, J., and He, Y. (2025) Dual-network hydrogel loaded with antler stem cells conditioned medium and EGCG promotes diabetic wound healing through antibacterial, antioxidant, anti-inflammatory, and angiogenesis, Mater. Today Bio, 31, 101612, https://doi.org/10.1016/j.mtbio.2025.101612.