In Silico Evaluation of the Anti-obesity and Hepatoprotective Potential of Epigallocatechin-Gallate (EGCG) and L-Theanine from Green Tea (Camellia sinensis)
DOI:
https://doi.org/10.53366/jimki.v12i1.846Keywords:
EGCG, in silico analysis, L-Theanine, obesity, orlistatAbstract
Background: Obesity is a multifactorial disease characterized by excessive accumulation of body fat. More than 1 billion people worldwide live with obesity, as 1 in 8 deaths of non-communicable diseases are caused by obesity in 2024. The primary objective of obesity management is to improve conditions and reduce the risk of developing comorbidities through lifestyle management combined with pharmacotherapy. The only accepted pharmacological treatment from the Food and Drug Administration (FDA) is orlistat. However, there are popular alternatives by utilizing compounds in green tea (Camellia sinensis).
Method: In silico analysis on EGCG and L-Theanine compounds found in Camellia sinensis were conducted to determine the feasibility of both compounds as alternatives pharmaceuticals candidates in managing obesity with hepatoprotective function using molecular docking techniques.
Results: The molecular docking result demonstrated EGCG’s affinity on PPAR?, the target receptor in standard drug orlistat, exhibited higher binding affinity compared to orlistat’s affinity on PPAR?. Additionally, docking of L-Theanine compound with PI3K protein showed functional activation of PI3K by L-Theanine as one of the primary hepatoprotective pathways.
Discussion: Higher binding affinity of EGCG through molecular docking indicates superior anti-obesity activity compared to standard drug orlistat. Hepatotoxicity side effects of EGCG can be mitigated by L-Theanine, which activates PI3K/Akt-NRF2, a hepatoprotective mechanism.
Conclusion: In silico analysis revealed potential benefits on two compounds in Camellia sinensis, EGCG and L-Theanine. Combination of both compounds can be perceived as a new opportunity in development of obesity therapy with better therapeutic effects and safer hepatic protection.
References
1. Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics. Metabolism. 2019 Mar;92:82–97.
2. Janić M, Janež A, El-Tanani M, Rizzo M. Obesity: Recent Advances and Future Perspectives. Biomedicines. 2025 Feb 5;13(2):368.
3. Lin X, Li H. Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front Endocrinol (Lausanne). 2021 Sep 6;12.
4. Vulchi J, Suryadevara V, Mohan P, Kamalanathan S, Sahoo J, Naik D, et al. Obesity and Metabolic Dysfunction-associated Fatty Liver Disease: Understanding the Intricate Link. J Transl Gastroenterol. 2023 Dec 25;1(2):74–86.
5. Jameson JL, Kasper DL, Longo DL, Fauci AS, Hauser SL, Loscalzo J. Harrison’s Principles of Internal Medicine. McGraw-Hill; 2018.
6. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation. 2014 Jun 24;129.
7. Cornier MA. A review of current guidelines for the treatment of obesity. Am J Manag Care. 2022 Dec 1;28(Suppl 15):S288–96.
8. Bansal AB, Patel P, Al Khalili Y. Orlistat. Treasure Island: StatPearls Publishing; 2024.
9. Qi X. Review of the Clinical Effect of Orlistat. IOP Conf Ser Mater Sci Eng. 2018 Jan;301:012063.
10. Radeva-Ilieva M, Stoeva S, Hvarchanova N, Georgiev KD. Green Tea: Current Knowledge and Issues. Foods. 2025 Feb 22;14(5):745.
11. Mokra D, Joskova M, Mokry J. 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. 2022 Dec 25;24(1):340.
12. Acosta L, Byham-Gray L, Kurzer M, Samavat H. Hepatotoxicity with High-Dose Green Tea Extract: Effect of Catechol-O-Methyltransferase and Uridine 5’-Diphospho-glucuronosyltransferase 1A4 Genotypes. J Diet Supply. 2023 Nov 2;20(6):850–69.
13. Dai H, Chen X, He J, Zheng P, Luo Y, Yu B, et al. Dietary L-theanine supplementation improves antioxidant capacity and lipid metabolism in finishing pigs. J Funct Foods. 2023 Nov;110:105831.
14. Zhu K, Zeng H, Yue L, Huang J, Ouyang J, Liu Z. The Protective Effects of L-Theanine against Epigallocatechin Gallate-Induced Acute Liver Injury in Mice. Foods. 2024 Apr 7;13(7):1121.
15. Laksmiani NPL, Putra IGP, I P. W. Nugraha IPW, Suwartawan IW, Ani NKS. Studi Potensi Sianidin Dan Peonidin Dari Ubi Jalar Ungu (Ipomoea Batatas L.) sebagai Agen Depigmentasi Secara In Silico. J Kim. 2019;13(1):34.
16. Binbay FA, Rathod DC, George AAP, Imhof D. Quality Assessment of Selected Protein Structures Derived from Homology Modeling and AlphaFold. Pharmaceuticals. 2023 Nov 29;16(12):1662.
17. Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr. 1993 Apr 1;26(2):283–91.
18. Salunke DM, Nair DT. Macromolecular structures: Quality assessment and biological interpretation. IUBMB Life. 2017 Aug 11;69(8):563–71.
19. Wang S, Lin Y, Gao L, Yang Z, Lin J, Ren S, et al. PPAR-γ integrates obesity and adipocyte clock through epigenetic regulation of Bmal1. Theranostics. 2022;12(4): 1589–606.
20. Faghfouri AH, Khajebishak Y, Payahoo L, Faghfuri E, Alivand M. PPAR-gamma agonists: Potential modulators of autophagy in obesity. Eur J Pharmacol [Internet]. 2021 Dec;912:174562. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0014299921007184
21. Park HS, Ju UI, Park JW, Song JY, Shin DH, Lee KH, et al. PPARγ neddylation essential for adipogenesis is a potential target for treating obesity. Cell Death Differ. 2016;23(8):1296–311.
22. Zhang Y, Zhang XY, Shi SR, Ma CN, Lin YP, Song WG, et al. Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation. Front Cardiovasc Med. 2024 Apr 18;11.
23. Spanoudaki M, Chrysafi M, Papadopoulou SK, Tsourouflis G, Pritsa A, Giaginis C. Naturally Occurring Compounds Targeting Peroxisome Proliferator Receptors: Potential Molecular Mechanisms and Future Perspectives for Promoting Human Health. Appl Sci. 2024 Nov 1;14(21):9994.
24. Li F, Gao C, Yan P, Zhang M, Wang Y, Hu Y, et al. EGCG Reduces Obesity and White Adipose Tissue Gain Partly Through AMPK Activation in Mice. Front Pharmacol. 2018 Nov 22;9.
25. Polianna de Brito G, Laura dos Santos F, Isabella Andreoni D, Adaliene Versiani Matos F. Effects of Phytotherapeutic Administration of Green Tea (Camellia sinensis) as a Treatment for Obesity: A Systematic Review of Clinical and Experimental Studies. J Nutr Med Diet Care. 2022 Dec 31;8(1).
26. Shamsan E, Almezgagi M, Gamah M, Khan N, Qasem A, Chuanchuan L, et al. The role of PI3k/AKT signaling pathway in attenuating liver fibrosis: a comprehensive review. Front Med. 2024 Mar 25;11. 329/full
27. Li J, Wang T, Liu P, Yang F, Wang X, Zheng W, et al. Hesperetin ameliorates hepatic oxidative stress and inflammation via the PI3K/AKT-Nrf2-ARE pathway in oleic acid-induced HepG2 cells and a rat model of high-fat diet-induced NAFLD. Food Funct. 2021;12(9):3898–918.
28. Cai ZY, Li XM, Liang JP, Xiang LP, Wang KR, Shi YL, et al. Bioavailability of Tea Catechins and Its Improvement. Molecules. 2018 Sep 13;23(9):2346.
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