In Silico Discovery of Green Tea and Green Coffee Bioactive Compounds Against IGF-1R, PPAR-α, and TLR4 as a Therapeutic Candidate for Metabolic Disorder
Article Sidebar
Main Article Content
Abstract
Metabolic syndrome (MetS) affects millions of people globally since it is linked to multiple risk factors, including obesity, dyslipidemia, high blood pressure, and type 2 diabetes mellitus (T2DM). Several molecular factors are contributing to MetS developments, including insulin-like growth factor-1 receptor (IGF-1R), peroxisome proliferator-activated receptor α (PPAR-α), and Toll-like receptor-4 (TLR4). Green tea (GT) and green coffee (GC) have unique flavors due to their bioactive compounds, which act as antioxidants, anti-inflammatories, and antihypertension. This work aimed to examine the pathways implicated in the development of MetS and discover
bioactive chemicals contained in GT and GC that have promising as inhibitors of IGF-1R, PPARα, and TLR4. The protein-protein interaction was explored using STRING, and the roles of bioactive compounds were evaluated in STITCH. The interaction between (-)-epigallocatechin (EC), catechin gallate (CG), epicatechin (EC), epigallocatechin gallate (EGCG), theobromine, trigonelline, chlorogenic acid, and caffeic acid against IGF-1R, PPAR-α, and TLR4 was measured by molecular docking. The present result demonstrated that eight protein interactions are involved in Mets development. The molecular docking result demonstrated that EGCG from GT has the
best binding affinity (kcal/mol) to IGF-1R (-9.1), PPAR-α (-9.5), and TLR4 (-6.5). In conclusion, bioactive compounds from GT were superior to GT through computational study. Both might be promising as anti-inflammatories and regulate the metabolism under MetS conditions.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Suliga E, Ciesla E, Lelonek M, Piechowska A, Gluszek S. Lifestyle elements and risk of metabolic syndrome in adults. Yen HY, editor. PLOS ONE. 2022; 17(9):e0275510. Doi: 10.1371/journal.pone.0275510
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020; 21(17):6275. Doi: 10.3390/ijms21176275
Herningtyas EH, Ng TS. Prevalence and distribution of metabolic syndrome and its components among provinces and ethnic groups in Indonesia. BMC Public Health. 2019; 19(1):377. Doi: 10.1186/s12889-019-6711-7
Regufe VMG, Pinto CMCB, Perez PMVHC. Metabolic syndrome in type 2 diabetic patients: a review of current evidence. Porto Biomed J. 2020; 5(6):e101. Doi:10.1097/j.pbj.0000000000000101
Aguirre GA, De Ita JR, de la Garza RG, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J Transl Med. 2016;1 4:3. Doi: 10.1186/s12967-015-0762-z
Monsalve FA, Pyarasani RD, Delgado-Lopez F, MooreCarrasco R. Peroxisome Proliferator-Activated Receptor Targets for the Treatment of Metabolic Diseases. Mediators Inflamm. 2013: e549627. Doi: 10.1155/2013/549627
Zeng F, Zheng J, Shen L, Herrera-Balandrano DD, Huang W, Sui Z. Physiological mechanisms of TLR4 in glucolipid metabolism regulation: Potential use in metabolic syndrome prevention. Nutr Metab Cardiovasc Dis. 2023; 33(1):38–46. Doi: 10.1016/j.numecd.2022.10.011
Atho'illah MF, Safitri YD, Nur'aini FD, Widyarti S, Tsuboi H, Rifa'i M. Elicited soybean extract attenuates proinflammatory cytokines expression by modulating TLR3/TLR4 activation in high−fat, high−fructose diet mice. J Ayurveda Integr Med. 2021; 12(1):43–51. Doi:
1016/j.jaim.2021.01.003
Dobrowolski P, Prejbisz A, Kuryłowicz A, Baska A, Burchardt P, Chlebus K, Dzida G, Jankowski P, Jaroszewicz J, Jaworski P, Kamiński K, Kapłon-Cieślicka A, Klocek M, Kukla M, Mamcarz A, Mastalerz-Migas A, Narkiewicz K, Ostrowska L, Śliż D, Tarnowski W, Wolf J, Wyleżoł M, Zdrojewski T, Banach M, Januszewicz A, Bogdański P. Metabolic syndrome – a new definition and management guidelines. Arch Med Sci. 2022; 18(5):1133–56. Doi: 10.5114/aoms/152921
Magkos F, Yannakoulia M, Chan JL, Mantzoros CS.Management of the Metabolic Syndrome and Type 2 Diabetes Through Lifestyle Modification. Annu Rev Nutr. 2009; 29(1):223–56. Doi: 10.1146/annurev-nutr-080508-141200
Lukitasari M, Nugroho D, Rohman M, Widodo N, Farmawati A, Hastuti P. Beneficial effects of green coffeeand green tea extract combination on metabolic syndrome improvement by affecting AMPK And PPAR-α gene expression. J Adv Pharm Technol Res. 2020; 11(2):81–85. Doi: 10.4103/japtr.JAPTR_116_19
Rohman MS, Lukitasari M, Kholis MN, Wahyuni NA, Chandra BR, Hermanto FE, Widodo N. Combination ofdecaffeinated green coffee and decaffeinated green tea ameliorates cardiomyopathy through cardiotrophin-1- dependent expression regulation in a metabolic syndrome rat
model: a proposed mechanism. Beni-Suef Univ J Basic Appl Sci. 2023; 12(1):53. Doi: 10.1186/s43088-023-00381-w
Prasetyawan S, Safitri A, Atho'illah MF, Rahayu S.Computational evaluation of bioactive compounds in Curcuma zanthorrhiza targeting SIRT1 and NFκB. BioTechnologia. 2023; 104(2):171–82. Doi: 10.5114/bta.2023.127206
Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015; 43(D1): D447-452. Doi:10.1093/nar/gku1003
Pertami SB, Arifah SN, Atho’illah MF, Budiono B. Active Compounds from Polyscias scutellaria Stimulate Breast Milk Production: In Silico Study on Serotonergic 5-HT2A Receptors and Prolactin Receptors. Trop J Nat Prod Res. 2021; 5(7): 1223–1229. Doi: 10.26538/tjnpr/v5i7.10
Huang H, Zhang G, Zhou Y, Lin C, Chen S, Lin Y, Mai S,Huang Z. Reverse Screening Methods to Search for the Protein Targets of Chemopreventive Compounds. Front Chem. 2018; 6:138. Doi: 10.3389/fchem.2018.00138
Adelusi TI, Adeyemi RO, Ashiru MA, Divine UC, Boyenle ID, Oyedele AK, Adewoye IM. Prediction of AntidiabeticCompounds in Curcuma longa–In vitro and In silico Investigations. Trop J Nat Prod Res. 2023; 7(10):4937–4944. Doi: 10.26538/tjnpr/v7i10.33
Dassault Systèmes BIOVIA. Discovery studio modeling environment, Version 4.5. San Diego: Dassault Systèmes; 2015.
Marušić M, Paić M, Knobloch M, Liberati Pršo AM. NAFLD, Insulin Resistance, and Diabetes Mellitus Type 2. Can J Gastroenterol Hepatol. 2021:6613827. Doi: 10.1155/2021/6613827
Bailes J, Soloviev M. Insulin-Like Growth Factor-1 (IGF-1) and Its Monitoring in Medical Diagnostic and in Sports. Biomolecules. 2021; 11(2):217. Doi: 10.3390/biom11020217
Li R, Pourpak A, Morris SW. Inhibition of the Insulin-like Growth Factor-1 Receptor (IGF1R) Tyrosine Kinase as a Novel Cancer Therapy Approach. J Med Chem. 2009; 52(16):4981. Doi: 10.1021/jm9002395
Wei R, Su Z, Mackenzie GG. Chlorogenic acid combined with epigallocatechin-3-gallate mitigates D-galactoseinduced gut aging in mice. Food Funct. 2023; 14(6):2684– 97. Doi: 10.1039/d2fo03306b
Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol. 2011; 82(12):1807. Doi: 10.1016/j.bcp.2011.07.093
Cheng Z, Zhang Z, Han Y, Wang J, Wang Y, Chen X, Shao Y, Cheng Y, Zhou W, Lu X, Wu Z. A review on anti-cancer effect of green tea catechins. J Funct Foods. 2020; 74(11):104172. Doi: 10.1016/j.jff.2020.104172
Pautsch A, Zoephel A, Ahorn H, Spevak W, Hauptmann R, Nar H. Crystal Structure of Bisphosphorylated IGF-1 Receptor Kinase: Insight into Domain Movements upon Kinase Activation. Structure. 2001; 9(10):955-965. Doi: 10.1016/S0969-2126(01)00655-4
Udenigwe CC, Rouvinen-Watt, K. The Role of Food Peptides in Lipid Metabolism during Dyslipidemia and Associated Health Conditions. Int. J. Mol. Sci. 2015; 16(5):9303-9313. Doi: 10.3390/ijms16059303
Chen H, Qi X, Guan K, Gu Y, Wang R, Li Q, Ma Y. Peptides released from bovine α-lactalbumin by simulated digestion alleviated free fatty acids-induced lipid accumulation in HepG2 cells. J. Func. Food. 2021; 85:104618. Doi:10.1016/j.jff.2021.104618
Pawlak M, Lefebvre P, Staels B. Molecular mechanism of PPARα action and its impact on lipid metabolism,inflammation and fibrosis in non-alcoholic fatty liver disease. J Hepatol. 2015; 62(3):720–33. Doi: 10.1016/j.jhep.2014.10.039
Corrales P, Vidal-Puig A, Medina-Gómez G. PPARs andMetabolic Disorders Associated with Challenged Adipose Tissue Plasticity. Int J Mol Sci. 2018; 19(7):2124. Doi: 10.3390/ijms19072124
Sae-tan S, Grove KA, Kennett MJ, Lambert JD. (−)- Epigallocatechin-3-gallate Increases the Expression of Genes Related to Fat Oxidation in the Skeletal Muscle of High FatFed Mice. Food Funct. 2011; 2011(2):111–6. Doi: 10.1039/C0FO00155D
Yan Y, Li Q, Shen L, Guo K, Zhou X. Chlorogenic acid improves glucose tolerance, lipid metabolism, inflammation and microbiota composition in diabetic db/db mice. Front Endocrinol. 2022; 13:1042044. Doi: 10.3389/fendo.2022.1042044
Li-Shan Y, Shuang C, Yan CBC, Xing-Bin Y, Wang YW,Qiu XY, Nima CR, Zhang Y, Zhang SF. Sichen Formula Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Blocking the TLR4 Signaling Pathways. Drug Des. Devel. Ther. 2023; 17: 297-312. Doi:10.2147/DDDT.S372981
Mukherjee S, Karmakar S, Babu SPS. TLR2 and TLR4 mediated host immune responses in major infectious diseases: a review. Braz J Infect Dis. 2016; 20(2):193–204. Doi: 10.1016/j.bjid.2015.10.011
Rehman K, Akash MSH. Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? J Biomed Sci. 2016; 23(1):87. Doi: 10.1186/s12929-016-0303-y
Hong Byun E, Fujimura Y, Yamada K, Tachibana H. TLR4 signaling inhibitory pathway induced by green tea polyphenol epigallocatechin-3-gallate through 67-kDa laminin receptor. J Immunol Baltim Md 1950. 2010;185(1):33–45. Doi: 10.4049/jimmunol.0903742
Saleh HA, Yousef MH, Abdelnaser A. The AntiInflammatory Properties of Phytochemicals and Their Effects on Epigenetic Mechanisms Involved in TLR4/NF-κB-Mediated Inflammation. Front Immunol. 2021; 24:12. Doi: 10.3389/fimmu.2021.606069
Jain S, Saha P, Syamprasad NP, Panda SR, Rajdev B, Jannu AK, Sharma P, Naidu VGM. Targeting TLR4/3 using chlorogenic acid ameliorates LPS+POLY I:C-induced acute respiratory distress syndrome via alleviating oxidative stressmediated NLRP3/NF-κB axis. Clin Sci. 2023; 137(10):785–805. Doi: 10.1042/CS20220625