Weak Anti-inflammatory and Anti-cancer Properties of Saffron

Document Type : Original paper






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


Background and objectives: Positive role of saffron in human health promotion has been investigated in widespread researches. Anticancer property, neuroprotection, protection of cardiovascular system and several positive properties are reported for saffron customers. The aim of this study was assessment of saffron weakness against light damage in rat retina. Methods: Gene profiles of control samples (C group) and light damage (L) groups were extracted from Gene Expression Omnibus (GEO) and compared with similar samples in the presence of saffron. The unprotected differentially expressed genes (DEGs) were evaluated via network analysis and pathway investigation.  The critical genes which were not protected by saffron were identified and discussed. Results: Numbers of 67 DEGs were investigated via protein-protein interaction (PPI) network analysis, pathway assessment, and action map investigation. Findings indicated that STAT1, JUN, FOS, and STAT3 were the crucial genes that were not protected by saffron against light damage in rat retina. Conclusion: It may be necessary that consumption of saffron require a suitable protocol to avoid from possible disadvantages; however, saffron is well known for its benefits in human nutrition. 


Main Subjects

[1] Evans WC. Trease and Evans Pharmacognosy. 16th Ed. London: Saunders, 2009.
[2] Ashktorab H, Soleimani A, Singh G, Amin A, Tabtabaei S, Latella G, Stein U, Akhondzadeh Sh, Solanki N, Gondré-Lewis MC, Habtezion A, Brim H. Saffron: the golden spice with therapeutic properties on digestive diseases. Nutrients. 2019; 11: 1-16.
[3] Moshiri M, Vahabzadeh M, Hosseinzadeh H. Clinical applications of saffron (Crocus sativus) and its constituents: a review. Drug Res. 2015; 65: 287-295.
[4] Rostagno MA, Prado JM. Natural product extraction principles and applications. Cambridge: The Royal Society of Chemistry, 2013.
[5] Khorasanchi Z, Shafiee M, Kermanshahi F, Khazaei M, Ryzhikov M, Parizadeh MR, Kermanshahi B, Ferns GA, Avan A, Hassanian SM. Crocus sativus a natural food coloring and flavoring has potent anti-tumor properties. Phytomed. 2018; 43: 21-27.
[6] Melnyk JP, Wang S, Marcone MF. Chemical and biological properties of the world's most expensive spice: saffron. Food Res Int. 2010; 43(8):1981-1989.
[7] Kamalipour M, Akhondzadeh S. Cardiovascular effects of saffron: an evidence-based review. J Tehran Heart Cent. 2011; 6(2): 59-61.
[8] Maccarone R, Di Marco S, Bisti S. Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Investig Ophthalmol Vis Sci. 2008; 49(3): 1254-1261.
[9] Di Marco F, Romeo S, Nandasena C, Purushothuman S, Adams C, Bisti S, Stone J. The time course of action of two neuroprotectants, dietary saffron and photobiomodulation, assessed in the rat retina. Am J Neurodegener Dis. 2013; 2(3): 208-220.
[10] Khayatnouri M, Safavi SE, Safarmashaei S, Babazadeh D, Mikailpourardabili B. The effect of saffron orally administration on spermatogenesis index in rat. Adv Environ Biol. 2011; 5(7): 1514-1521.
[11] Bathaie SZ, Mousavi SZ. New applications and mechanisms of action of saffron and its important ingredients. Crit Rev Food Sci Nutr. 2010; 50(8): 761-786.
[12] Mallikarjuna Swamy B, Ahmed HU, Henry A, Mauleon R, Dixit S, Vikram P, Tilatto R, Verulkar SB, Perraju P, Mandal NP, Variar M, Robin S, Chandrababu R, Singh ON, Dwivedi JL, Das SP, Mishra KK, Yadaw RB, Aditya TL, Karmakar B, Satoh K, Moumeni A, Kikuchi S, Leung H, Kumar A. Genetic, physiological, and gene expression analyses reveal that multiple QTL enhance yield of rice mega-variety IR64 under drought. PLoS One. 2013; Article ID e62795.
[13] Bouwens M, Van de Rest O, Dellschaft N, Bromhaar MG, de Groot LC, Geleijnse JM, Müller M, Afman LA. Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr. 2009; 90(2): 415-424.
[14] Mead MN. Nutrigenomics: the genome-food interface. Environ Health Perspect. 2007; 115(12): 582-589.
[15] 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. Mol Vis. 2010; 16: 1801-1822.
[16] Nezamdoost Z, Saghebjoo M, Hoshyar R, Hedayati M, Keska A. High-intensity training and saffron: effects on breast cancer-related gene expression. Med Sci Sports Exerc. In press.
[17] Keller M, Fankhauser S, Giezendanner N, König M, Keresztes F, Danton O, Hamburger M, Butterweck V, Potterat O. Saponins from saffron corms inhibit the secretion of pro-inflammatory cytokines at both protein and gene levels. Planta Med. 2019; 85: 1407.
[18] Motamedrad M, Shokouhifar A, Hemmati M, Moossavi M. The regulatory effect of saffron stigma on the gene expression of the glucose metabolism key enzymes and stress proteins in streptozotocin-induced diabetic rats. Res Pharm Sci. 2019; 14(3): 255-262.
[19] Azad RK, Shulaev V. Metabolomics technology and bioinformatics for precision medicine. Brief Bioinform. 2019; 20(6): 1957-1971.
[20] Brown J, Phillips AR, Lewis DA, Mans M-A, Chang Y, Tanguay RL, Peterson ES, Waters KM, Tilton SC. Bioinformatics resource manager: a systems biology web tool for microRNA and omics data integration. BMC Bioinform. 2019; 20(1): 1-8.
[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): 257-263.
[22] Rezaei-Tavirani M, Tavirani MR, Azodi MZ, Farshi HM, Razzaghi M. Evaluation of skin response after erbium: yttrium-aluminum-garnet laser irradiation: a network analysis approach. J Lasers Med Sci. 2019; 10(3): 194-199.
[23] Asadzadeh-Aghdaei H, Zadeh-Esmaeel MM, Esmaeili S, Rezaei–Tavirani M, Rezaei-Tavirani S, Mansouri V, Montazer F. Effects of high fat medium condition on cellular gene expression profile: a network analysis approach. Gastroenterol Hepatol Bed Bench. 2019; 12(S1): 130-135.
[24] Mlecnik B, Galon J, Bindea G. Automated exploration of gene ontology term and pathway networks with ClueGO-REST. Bioinformatics. 2019; 35(19): 3864-3866.
[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] Rezaei-Tavirani M, Rezaei-Tavirani S, Ahmadi N, Naderi N, Abdi S. Pancreatic adenocarcinoma protein-protein interaction network analysis. Gastroenterol Hepatol Bed Bench. 2017; 10(Sl1): 85.
[27] Angel P, Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991; 1072(2-3): 129-157.
[28] Sassone-Corsi P, Ransone LJ, Lamph WW, Verma IM. Direct interaction between fos and jun nuclear oncoproteins: role of the'leucine zipper'domain. Nature. 1988; 336(6200): 692-695.
[29] Abdullaev F, Espinosa-Aguirre J. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev. 2004; 28(6): 426-432.
[30] Durbin JE, Hackenmiller R, Simon MC, Levy DE. Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease. Cell. 1996; 84(3): 443-450.
[31] Dupuis S, Jouanguy E, Al-Hajjar S, Fieschi C, Al-Mohsen IZ, Al-Jumaah S, Yang K, Chapgier A, Eidenschenk C, Eid P, Al Ghonaium A, Tufenkeji H, Frayha H, Al-Gazlan S, Al-Rayes H, Schreiber RD, Gresser I, Casanova JL. Impaired response to interferon-α/β and lethal viral disease in human STAT1 deficiency. Nat Genet. 2003; 33(3): 388-391.
[32] Welte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE, Bothwell AL, Fikrig E, Koni PA, Flavell RA, Fu XY. STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proc Natl Acad Sci USA.  2003; 100(4): 1879-1884.
[33] Lovato P, Brender C, Agnholt J, Kelsen J, Kaltoft K, Svejgaard A, Eriksen KW, Woetmann A, Odum N. Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease. J Biol Chem. 2003; 278(19): 16777-16781.