Prediction of Coffee Effects in Rats with Healthy and NAFLD Conditions Based on Protein-Protein Interaction Network Analysis

Document Type : Original paper


1 Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Traditional Medicine and Materia Medica Research Center and Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


Background and objectives: Non-alcoholic fatty liver disease (NAFLD) is a common liver condition. On the other hand, coffee consumption has shown promising for gastrointestinal diseases.  Detection of the most valuable biomarkers of decaffeinated coffee treatment in healthy and non-alcoholic fatty liver disease conditions was the aim of the present study. Methods: A previous proteomics study about effect of decaffeinated coffee (1.5 mL daily drinking coffee for two months) on protein expression change of rat liver was selected for protein-protein interaction (PPI) network analysis via Cytoscape v.3.7.1 and the related applications. The most central proteins with regards to a high degree and betweenness centralities in the coffee treatment condition of healthy and NAFLD were then analyzed by ClueGO for biological process (BP) derivation. Results: HSPA5, HSPA4, HSPA9, HSPA7, PARK7, HSP90AA1, P4HB, PRDX1, and PDIA3 were introduced as central proteins, which are involved in folding and antioxidant activities. Conclusion:  There is a complicated combination of the components in coffee; some elements are involved in liver protection against NAFLD and the others are in contrast.


Main Subjects

[1] Butt MS, Sultan MT. Coffee and its consumption: benefits and risks. Crit Rev Food Sci Nutr. 2011; 51(4): 363-373.
[2] Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC, Parkes J. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. Br Med J. 2017; 359:  1-17.
[3] Urgert R, Meyboom S, Kuilman K, Rexwinkel H, Vissers MN, Klerk M, Katan MB. Comparison of effect of cafetiere and filtered coffee on serum concentrations of liver aminotransferases and lipids: six month randomised controlled trial. Br Med J. 1996; 313(7069): 1362-1366.
[4] Bambha K, Wilson LA, Unalp A, Loomba R, Neuschwander-Tetri BA, Brunt EM, Bass NM. Nonalcoholic steatohepatitis clinical research, coffee consumption in NAFLD patients with lower insulin resistance is associated with lower risk of severe fibrosis. Liver Int. 2014; 34(8): 1250-1258.
[5] Molloy JW, Calcagno CJ, Williams CD, Jones FJ, Torres DM, Harrison SA. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology. 2012; 55(2): 429-436.
[6] Wijarnpreecha K, Thongprayoon C, Ungprasert P. Coffee consumption and risk of nonalcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2017; 29(2): 8-12.
[7] Brezova V, Slebodova A, Stasko A. Coffee as a source of antioxidants: an EPR study. Food Chem. 2009; 114(3): 859-868.
[8] Helal MG, Ayoub SE, Elkashefand WF, Ibrahim TM. Caffeine affects HFD-induced hepatic steatosis by multifactorial intervention. Hum Exp Toxicol. 2018; 37(9): 983-990.
[9] Salomone F, Galvano F, Li Volti G. Molecular bases underlying the hepatoprotective effects of coffee. Nutrients. 2017; 9(1): 85-97.
[10] Assy N, Nasser G, Kamayse I, Nseir W, Beniashvili Z, Djibre A, Grosovski M. Soft drink consumption linked with fatty liver in the absence of traditional risk factors. Can J Gastroenterol. 2008; 22(10): 811-816.
[11] Alferink LJM, Kiefte-de Jong JC. Potential mechanisms underlying the ole of coffee in liver health. Semin Liver Dis. 2018; 38(3): 193-214.
[12] Shetty A, Syn WK. Current treatment options for nonalcoholic fatty liver disease. Curr Opin Gastroenterol. 2019; 35(3): 168-176.
[13] Brandt A, Nier A, Jin CJ, Baumann A, Jung F, Ribas V, García-Ruiz C, Fernández-Checa JC, Bergheim I. Consumption of decaffeinated coffee protects against the development of early non-alcoholic steatohepatitis: role of intestinal barrier function. Redox Biol. 2019; 21: 1-13
[14] Cheah MC, Mc Cullough AJ, Goh GB. Dietary manipulations for nonalcoholic fatty liver disease (NAFLD). bioactive food as dietary interventions for diabetes. 2nd ed., Elsevier, 2019.
[15] Chen YP, Lu FB, Hu YB, Xu LM, Zheng MH, Hu ED.  A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease. Clin Nutr. In press.
[16] Zamanian-Azodi M, Rezaei-Tavirani M, Mahboubi M, Hamidpour M, Rezaei Tavirani M, Hamdieh M, Rostami-Nejad M, Nejadi N, Derakhshan MK. Serum proteomic study of women with obsessive-compulsive disorder, washing subtype. Basic Nlin Neurosci. 2018; 9(5): 337-346.
[17] Zamanian-Azodi M, Rezaei-Tavirani M, Rezaei-Tavirani M, Vafaee R, Rostami-Nejad M. Nasopharyngeal carcinoma protein interaction mapping analysis via proteomic approaches. Asian Pac J Cancer Prev. 2018; 19(3): 845-851.
[18] Zamanian-Azodi M, Rezaei-Tavirani M, Rostami-Nejad M, Rezaei-Tavirani M. Comparative bioinformatics characteristic of bladder cancer stage 2 from stage 4 expression profile: a network-based study. Galen Med J. 2018; 7:1-8.
[19] Salomone F, Li Volti G, Vitaglione P, Morisco F, Fogliano V, Zappalà A, Palmigiano A, Garozzo D, Caporaso N, D'Argenio G, Galvano F. Coffee enhances the expression of chaperones and antioxidant proteins in rats with nonalcoholic fatty liver disease. Transl Res. 2014; 163(6): 593-602.
[20] Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003. 13(11): 2498-2504.
[21] Rostami-Nejad M, Rezaei Tavirani S, Mansouri V, Jahani-Sherafat S, Moravvej Farshi H. Gene expression profile analysis of colon cancer grade II into grade III transition by using system biology. Gastroenterol Hepatol Bed Bench. 2019; 12(1): 60-66.
[22] Rezaei-Tavirani M, Rezaei-Taviran S, Mansouri M, Rostami-Nejad M, Rezaei-Tavirani M. Protein-protein interaction network analysis for a biomarker panel related to human esophageal adenocarcinoma. Asian Pac J Cancer Prev. 2017; 18(12): 3357-3363.
[23] Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pagès F, Trajanoski Z, Galon J. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25(8): 1091-1093.
[24] Affonso RC, Voytena AP, Fanan S, Pitz H, Coelho DS, Horstmann AL, Pereira A, Uarrota VG, Hillmann MC, Varela LA, Ribeiro-do-Valle RM, Maraschin M. Phytochemical composition, antioxidant activity, and the effect of the aqueous extract of coffee (Coffea arabica L.) bean residual press cake on the skin wound healing. Oxid Med Cell Longev. 2016; Article ID 1923754.
[25] Zhang J, Fan N, Peng Y. Heat shock protein 70 promotes lipogenesis in HepG2 cells. Lipids Health Dis. 2018; 17(1): 73-82.
[26] Wheeler MC, Gekakis N. Hsp90 modulates PPARγ activity in a mouse model of nonalcoholic fatty liver disease. J Lipid Res. 2014; 55(8): 1702-1710.
[27] Singh R, Wang Y, Xiang Y, Tanaka KE, Gaarde WA, Czaja MJ. Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology. 2009; 49(1): 87-96.
[28] Rhee SG, Woo HA, Kil IS, Bae SH. Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides. J Biol Chem. 2012; 287(7): 4403-4410.
[29] Kim YJ, Lee WS, Ip C, Chae HZ, Park EM, Park YM. Prx1 suppresses radiation-induced c-Jun NH2-terminal kinase signaling in lung cancer cells through interaction with the glutathione S-transferase Pi/c-Jun NH2-terminal kinase complex. Cancer Res. 2006; 66(14): 7136-7142.
[30] Xia W, Zhuang J, Wang G, Ni J, Wang J, Ye Y. P4HB promotes HCC tumorigenesis through downregulation of GRP78 and subsequent upregulation of epithelial-to-mesenchymal transition. Oncotarget. 2017; 8(5): 8512-8521.
[31] Molloy JW, Calcagno CJ, Williams CD, Jones FJ, Torres DM, Harrison SA. Association of coffee and caffeine consumption with fatty liver disease, nonalcoholic steatohepatitis, and degree of hepatic fibrosis. Hepatology, 2012; 55(2): 429-436.
[32] Vitaglione P, Morisco F, Mazzone G, Amoruso DC, Ribecco MT, Romano A, Fogliano V, Caporaso N, D'Argenio G. Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins. Hepatology. 2010; 52(5): 1652-1661.
[33] Wang Q, Dai X, Yang W, Wang H, Zhao H, Yang F, Yang Y, Li J, Lv X. Caffeine protects against alcohol-induced liver fibrosis by dampening the cAMP/PKA/CREB pathway in rat hepatic stellate cells. Int Immunopharmacol. 2015; 25(2): 340-352.
[34] McCusker RR, Goldberger BA, Cone EJ. Caffeine content of specialty coffees. J Anal Toxicol. 2003; 27(7): 520-522.
[35] Moreira AS, Nunes FM, Domingues MR, Coimbra MA. Coffee melanoidins: structures, mechanisms of formation and potential health impacts. Food Funct. 2012; 3(9): 903-915.