Evaluating of Gene Expression Alteration after Garlic Consumption, Analyzing through Bioinformatics Approach

Document Type : Research article


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

2 Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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

4 Physiotherapy Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

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

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


Molecular study of garlic as a popular food ingredient could better understand its health benefits such as immunological effects. For this aim, effects of garlic on the spleen and possible side effects including oxidative stress increment, the molecular mechanism is investigated through network analysis of differentially expressed genes in the treatment of garlic. Protein-protein interaction (PPI) network analysis of spleen gene expression profile of Mus musculus (8-week old male C57BL/6J mice) in garlic treatments from a microarray study with the code of GSE10344 was analyzed via GEO2R software. Furthermore, Cytoscape V 3.7.1 was applied to construct and analyze a network of up- and down-regulated genes. The differentially expressed genes (DEGs) were analyzed via the CluePedia plugin of Cytoscape to determine expression patterns. After the identification of central nodes, an action map was created. A total of 77 DEGs were achieved which were including 40 up-regulated and 37 Down-regulated. The centrality analysis of the network indicated that Vcan, Lamb1, and Ltbp1 are hubs and Glra1, Wdr17, Nefl, and Becn1 are bottlenecks. Mutual regulatory connections between hubs and Alb and App (as two non-queried hubs) were determined. The findings indicate that garlic effect on the spleen and its mechanism may be involved mostly with App dysregulation.

Graphical Abstract

Evaluating of Gene Expression Alteration after Garlic Consumption, Analyzing through Bioinformatics Approach


  1. Huang CH, Hsu FY, Wu YH, Zhong L, Tseng MY, Kuo CJ, Hsu AL, Liang SS and Chiou SH. Analysis of lifespan-promoting effect of garlic extract by an integrated metabolo-proteomics approach. J. Nutr. Biochem. (2015) 26: 808-17.
  2. Bayan L, Koulivand PH and Gorji A. Garlic: a review of potential therapeutic effects. Avicenna J. phytomed. (2014) 4: 1-14.
  3. Gorinstein S, Leontowicz H, Leontowicz M, Namiesnik J, Najman K, Drzewiecki J, Cvikrova M, Martincova O,  Katrich E and  Trakhtenberg S. Comparison of the main bioactive compounds and antioxidant activities in garlic and white and red onions after treatment protocols. J. Agric. Food Chem. (2008) 56: 4418-26.
  4. Akgül B, Lin KW, Yang HMO, Chen YH, Lu TH, Chen CH Kikuchi T, Chen YT and TU CP. Garlic accelerates red blood cell turnover and splenic erythropoietic gene expression in mice: evidence for erythropoietin-independent erythropoiesis. PloS one. (2010) 5: e15358.
  5. Petropoulos S, Fernandes Â, Barros L, Ciric A, Sokovic M and Ferreira IC. Antimicrobial and antioxidant properties of various Greek garlic genotypes. Food chem. (2018) 245:7-12.
  6. Kim WT, Seo S-P, Byun YJ, Kang H-W, Kim Y-J, Lee SC, Jeong P, Seo Y,  Choe SY, Kim DJ, Kim SK, Moon SK Choi YH, Lee GT  Kim IY Yun SJ and Kim WJ. Garlic extract in bladder cancer prevention: Evidence from T24 bladder cancer cell xenograft model, tissue microarray, and gene network analysis. Int. J. Oncol. (2017) 51: 204-12.
  7. Lan X, Sun H, Liu J, Lin Y, Zhu Z, Han X, Sun X, Li X, Zhang H and Tang Z. Effects of garlic oil on pancreatic cancer cells. Asian Pac. J. of Cancer Prev. (2013) 14: 5905-10.
  8. Fleischauer AT, Poole C, Arab L. Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers. Am. J. Clin Nutr. (2000) 72:1047-52.
  9. Seo MJ, Kang BW, Park JU, Kim MJ, Lee HH, Ryu EJ, Joo WH, Kim KH and Jeong YK. Effect of black garlic extract on cytokine generation of mouse spleen cells. J. Life Sci. (2013) 23: 63-8.
  10. Andrew UO, Ozoko LEC, Kingsley IA, Mamerhi ET, Beauty E. Histologic effect of garlic extract on the spleen of adult wistar rat. J Pharm. Biol Sci. (2017) 2:1-4.
  11. Rezaei-Tavirani M, Rezaei-Tavirani M and Zamanian Azodi M. The bioinformatics aspects of gene screening of HT-29, human colon cell line treated with caffeic acid. Gastroenterol. Hepatol. Bed Bench. (2019) 12: 246-53.
  12. Zamanian-Azodi M and Rezaei-Tavirani M. Investigation of health benefits of cocoa in human colorectal cancer cell line, HT-29 through interactome analysis. Gastroenterol. and Hepatol. Bed Bench. (2019) 12: 67-73.
  13. Barrett T, Wilhite SE, Ledoux P, Evangelista C and Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL,  Serova N,  Davis S and Alexandra Soboleva A. NCBI GEO: archive for functional genomics data sets update. Nucleic Acids Res. (2012) 41: D991-5.
  14. Yeh YY and Yeh SM. Garlic reduces plasma lipids by inhibiting hepatic cholesterol and triacylglycerol synthesis. Lipids. (1994) 29:189-93.
  15. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. (2003) 13: 2498-504.
  16. Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, Jensen LJ and  Mering CV. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic acids Res. (2016) 45: D362-8.
  17. Bindea G, Galon J and Mlecnik B. CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics. (2013) 29 :661-3.
  18. Zamani A, Vahidinia A and Ghannad MS. The effect of garlic consumption on Th1/Th2 cytokines in phytohemagglutinin (PHA) activated rat spleen lymphocytes. Phytother. Res. (2009) 23: 579-81.
  19. Hamlaoui-Gasmi S, Mokni M, Limam N, Limam F, Amri M, Aouani E and Marzouki L. Grape seed extract mitigates garlic-induced oxidative stress in rat spleen and plasma. J Med. Plant. Res. (2011) 5: 6076-84.
  20. Gu X, Wu H and Fu P. Allicin attenuates inflammation and suppresses HLA-B27 protein expression in ankylosing spondylitis mice. Biomed. Res. Int. (2013) 2013: 1-6
  21. Kimura A, Kakinuma K, Yonezawa S and Takahashi T. Expression of β-amyloid precursor protein in the porcine ovary. Zool. Sci. (2000) 17:769-78.
  22. Rasouli J, Lekhraj R, Ozbalik M, Lalezari P, andCasper D. Brain-spleen inflammatory coupling: a literature review. The Einstein J. Biol. Med. (2011) 27: 74-77.
  23. Paris D, Ait-Ghezala G, Bachmeier C, Laco G, Beaulieu-Abdelahad D, Lin Y, Jin C, Crawford F and Mullan M. The spleen tyrosine kinase (Syk) regulates Alzheimer amyloid-β production and Tau hyperphosphorylation. J Biol. Chem. (2014) 289: 33927-44.
  24. Chauhan NB. Effect of aged garlic extract on APP processing and tau phosphorylation in Alzheimer's transgenic model Tg2576. J. Ethnopharmacol. (2006) 108: 385-94.
  25. Ray B, Chauhan NB and Lahiri DK. The “Aged Garlic Extract”(AGE) and One of its Active Ingredients S-Allyl-LCysteine (SAC) as Potential Preventive and Therapeutic Agents for Alzheimer's Disease (AD). Curr. Med. Chem. (2011) 18: 3306-13.
  26. Takano T, Sada K and Yamamura H. Role of protein-tyrosine kinase syk in oxidative stress signaling in B cells. Antioxid. Redox Signal. (2002) 4: 533-41.