Assessment of Saffron Neuroprotective Properties in Rat Retina versus Light Damage

Document Type: Original paper

Authors

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

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

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

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

5 Firoozabadi Hospital, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

6 Proteomics Research Center, Department of Emergency Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Background and objectives: Crocus sativus L. (Iridaceae) commonly known as saffron, is a popular spice which is used for its pleasant aroma and favored color. Regarding the previous reports about the neuroprotective behavior of saffron or its constituents, in the present work, the neuroprotective property of saffron in rat retina was investigated against light damage in a system biology study. Methods: Retina gene profiles of 4 groups (each group including 3 samples) of rats (control; C light damage; L, Saffron; S, and saffron-light damage; SL) which are included in GSE22818 were extracted from Gene Expression Omnibus (GEO).  The significant differentially expressed genes (DEGs) from C-L groups analysis which are not included in S-SL comparison were screened by pathway analysis to find the critical protected genes against light damage by saffron. Results: Numbers of 46 gene were protected by saffron versus light damage significantly. The findings revealed that Casp3, Myd88, Birc3, Tnfrsf1a, Myc, Nfkb2, Fgf2 were the important protected genes by saffron against light damage. “MAPK signaling pathway” and “apoptosis” were highlighted as important related pathways for 46 DEGs. Conclusion: Saffron protects a part of light damage which is controlled mostly by Casp3, Myd88, Birc3, Tnfrsf1a, Myc, Nfkb2, Fgf2. It seems other parts of damage should be studied in more details to find a complete prospective of molecular mechanism of light damage effect on retina.  

Keywords

Main Subjects


[1] Mousavi SZ, Bathaie SZ. Historical uses of saffron: identifying potential new avenues for modern research. Avicenna J Phytomed. 2011; 1(2): 57-66.

[2] Hosseinzadeh H. Saffron: a herbal medicine of third millennium. Jundishapur J Nat Pharm Prod. 2014; 9(1): 1-2.

[3] Akhondzadeh S, Sabet MS, Harirchian M, Togha M, Cheraghmakani H, Razeghi S, Hejazi SSh, Yousefi MH, Alimardani R, Jamshidi A, Zare F, Moradi A. Saffron in the treatment of patients with mild to moderate Alzheimer’s disease: a 16‐week, randomized and placebo‐controlled trial. J Clin Pharm Ther. 2010; 35(5): 581-588.

[4] Kamalipour M, Akhondzadeh S. Cardiovascular effects of saffron: an evidence-based review. J Tehran Heart Cent. 2011; 6(2): 59-61.

[5] Rao SV, Muralidhara, Yenisetti SC, Rajini PS. Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of Parkinsonism. Neurotoxicology. 2016; 52: 230-242.

[6] Skladnev NV, Johnstone DM. Neuroprotective properties of dietary saffron: more than just a chemical scavenger? Neural Regen Res. 2017; 12(2): 210-211.

[7] Azari H, Ebrahimi S, Saeb S, Ghanbari A, Peyravian F, Mokarram P. The Effect of saffron aquatic extract and crocin on the differentiation of neural stem cells into oligodendrocyte precursor cells. Shiraz EMed J. 2018; 19(3): 1-7.

[8] Sadeghnia HR, Shaterzadeh H, Forouzanfar F, Hosseinzadeh H. Neuroprotective effect of safranal, an active ingredient of Crocus sativus, in a rat model of transient cerebral ischemia. Folia Neuropathol. 2017; 55(3): 206-213.

[9] Bisti S, Maccarone R, Falsini B. Saffron and retina: neuroprotection and pharmacokinetics. Vis Neurosci. 2014; 31(4-5): 355-361.

[10] Amin A, Hamza AA, Bajbouj K, Ashraf SS, Daoud S. Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology. 2011; 54(3): 857-867.

[11] Hoshyar R, Mollaei H. A comprehensive review on anticancer mechanisms of the main carotenoid of saffron, crocin. J Pharm Pharmacol. 2017; 69(11): 1419-1427.

[12] Sun X, Vilar S, Tatonetti NP. High-throughput methods for combinatorial drug discovery. Sci Transl Med. 2013; Article ID 24089409.

[13] Ovesná J, Slabý O, Toussaint O, Kodíček M, Maršík P, Pouchová V, Vanĕk T. High throughput ‘omics’ approaches to assess the effects of phytochemicals in human health studies. Br J Nutr. 2008; 99(ES1): 127-134.

[14] Wheelock CE, Goss VM, Balgoma D, Nicholas B, Brandsma J, Skipp PJ, Snowden S, Burg D, D'Amico A, Horvath I, Chaiboonchoe A, Ahmed H, Ballereau S, Rossios C, Chung KF, Montuschi P, Fowler SJ, Adcock IM, Postle AD, Dahlén SE, Rowe A, Sterk PJ, Auffray C, Djukanovic R. Application of’omics technologies to biomarker discovery in inflammatory lung diseases. Eur Respir J. 2013; 42(3): 802-825.

[15] Baxevanis AD, Bader G, Wishart D. Bioinformatics: John Wiley & Sons, 2020.

[16] Perroud B, Lee J, Valkova N, Dhirapong A, Lin PY, Fiehn O, Kültz D, Weiss RH. Pathway analysis of kidney cancer using proteomics and metabolic profiling. Mol Cancer. 2006; 5(1): 1-17.

[17] Helleman J, Smid M, Jansen MP, Vander Burg ME, Berns EM. Pathway analysis of gene lists associated with platinum-based chemotherapy resistance in ovarian cancer: the big picture. Gynecol Oncol. 2010; 117(2): 170-176.

[18] Jack XY, Sieuwerts AM, Zhang Y, Martens JW, Smid M, Klijn JG, Wang Y, Foekens JA. Pathway analysis of gene signatures predicting metastasis of node-negative primary breast cancer. BMC Cancer. 2007; 7(1): 1-14.

[19] Zali H, Rezaei-Tavirani M, Vafaee R, Rezaei-Tavirani M. Gastric cardia adenocarcinoma pathway analysis. Gastroenterol Hepatol Bed Bench. 2013; 6(S1): 11-18.

[20] Tavirani MR, Tavirani SR, Rostami FT. Biochemical pathway analysis of gastric atrophy. Gastroenterol Hepatol Bed Bench. 2018; 11(2): 118-124.

[21] Rostami-Nejad M, Rezaei-Tavirani M, Zadeh-Esmaeel MM, RezaeiTavirani S, Akbari Z, Esmaeili S, Okhovatian F. Assessment of cytokine-mediated signaling pathway dysregulation in arm skin after CO2 laser therapy. J Lasers Med Sci. 2019; 10(4): 1-7.

[22] Natoli R, Zhu Y, Valter K, Bisti S, Eells J, Stone J. Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina. Molecular Vis. 2010; 16: 1801-1822.

[23] Mlecnik B, Galon J, Bindea G. Automated exploration of gene ontology term and pathway networks with ClueGO-REST. Bioinformatics. 2019; 35(19): 3864-3866.

[24] KEGG: Kyoto Encyclopedia of Genes and Genomes. [Accessed 2020]. Available from https://www.genome.jp/kegg/

[25] Bindea G, Galon J, Mlecnik B. CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics. 2013; 29(5): 661-663.

[26] Khatri P, Sirota M, Butte AJ. Ten years of pathway analysis: current approaches and outstanding challenges. PLoS Comput Biol. 2012; 8(2): 1-10.

[27] Papin JA, Stelling J, Price ND, Klamt S, Schuster S, Palsson BO. Comparison of network-based pathway analysis methods. Trends Biotechnol. 2004; 22(8): 400-405.

[28] Piccardi M, Marangoni D, Minnella AM, Savastano MC, Valentini P, Ambrosio L, Capoluongo E, Maccarone R, Bisti S, Falsini B. A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function. Evid Based Complement Altern Med. 2012; Article ID 429124.

[29] Bajbouj K, Schulze-Luehrmann J, Diermeier S, Amin A, Schneider-Stock R. The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines. BMC Complement Altern Med. 2012; 12(1): 1-9.

[30] Kangas A, Nicholson DW, HoÈlttaÈ E. Involvement of CPP32/Caspase-3 in c-Myc-induced apoptosis. Oncogene. 1998; 16(3): 387-398.

[31] Keller U, Huber J, Nilsson JA, Fallahi M, Hall MA, Peschel C, Cleveland JL. Myc suppression of Nfkb2 accelerates lymphomagenesis. BMC Cancer. 2010; 10 :1-10.

[32] McHale CM, Zhang L, Lan Q, Li G, Hubbard AE, Forrest MS, Vermeulen R, Chen J, Shen M, Rappaport SM, Yin S, Smith MT, Rothman N. Changes in the peripheral blood transcriptome associated with occupational benzene exposure identified by cross-comparison on two microarray platforms. Genomics. 2009; 93(4): 343-349.

[33] Kim EK, Choi EJ. Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta. 2010; 1802(4): 396-405.

[34] Lowe SW, Lin AW. Apoptosis in cancer. Carcinogenesis. 2000; 21(3): 485-495.

[35] Carson DA, Ribeiro JM. Apoptosis and disease. Lancet. 1993; 341(8855): 1251-1254.

[36] Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol. 2000; 1(2): 120-130.