Antioxidant Activity, Metal Chelating Ability and DNA Protective Effect of the Hydroethanolic Extracts of Crocus sativus Stigmas, Tepals and Leaves
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Plant Material
2.3. Preparation of Plant Material
2.4. Preparation of Hydroethanolic Extracts
2.5. Animals
2.6. Determination of Total Polyphenols
2.7. Antioxidant Activity
2.7.1. Antiradical Activity by DPPH Method
2.7.2. Ferric Reducing Antioxidant Power (FRAP)
2.7.3. Bleaching Test for β-Carotene
2.8. Metal Chelating Power
2.8.1. Iron Chelation Test
2.8.2. Copper Chelation Test
2.9. DNA Protective Effect
2.9.1. Collection and Treatment of Cells
- -
- Genotoxic effect
- -
- DNA-protective effect
- -
- Positive control
- -
- Negative control
2.9.2. Comet Assay
2.9.3. Microscopic Observation
2.10. Statistical Analysis
3. Results
3.1. Total Polyphenol Content
3.2. Antioxidant Activity
3.2.1. Antiradical Activity by DPPH Method
3.2.2. Effect on the Ferric Reducing Antioxidant Power
3.2.3. Effect on the Bleaching of β-Carotene
3.3. Metal Chelating Power
3.3.1. Iron Chelating Power
3.3.2. Copper Chelating Power
3.4. Genotoxic Effect on Rat Leukocytes
3.5. DNA-Protective Effect in Streptozotocin-Intoxicated Leukocytes
3.6. DNA-Protective Effect in Alloxan-Intoxicated Leukocytes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Manzo, A.; Panseri, S.; Bertoni, D.; Giorgi, A. Economic and qualitative traits of Italian Alps saffron. J. Mt. Sci. 2015, 12, 1542–1550. [Google Scholar] [CrossRef]
- Lim, T.K. Crocus sativus. In Edible Medicinal and Non Medicinal Plants: Flowers; T.K. Lim, Ed.; Springer: Dordrecht, The Netherlands, 2014; Volume 8, pp. 77–136. [Google Scholar]
- MAPM. 2019. Available online: https://www.agriculture.gov.ma/fr/filiere/safran (accessed on 4 February 2019).
- Melnyk, P.J.; Wang, S.; Marcone, M.F. Chemical and biological properties of the world’s most expensive spice: Saffron. Food Res. Int. 2010, 43, 1981–1989. [Google Scholar] [CrossRef]
- Mousavi, Z.S.; Bathaie, S.Z. Historical uses of saffron: Identifying Potential New Avenues for Modern Research. Avicenna J. Phytomedicine 2011, 1, 57–66. [Google Scholar]
- Sampathu, S.R.; Shivashankar, S.; Lewis, Y.S.; Wood, A.B. Saffron (Crocus Sativus Linn.)—Cultivation, processing, chemistry and standardization. CRC Crit. Rev. Food Sci. Nutr. 1984, 20, 123–157. [Google Scholar] [CrossRef]
- Karimi, E.; Oskoueian, E.; Hendra, R.; Jaafar, H.Z. Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity. Molecules 2010, 15, 6244–6256. [Google Scholar] [CrossRef] [Green Version]
- Abdullaev, F. Saffron (Crocus sativus L.) and its possible role in the prevention of cancer. Recent Prog. Med. Plants 2003, 8, 53–67. [Google Scholar]
- Salomi, M.; Nair, S.C.; Panikkar, K. Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. Nutr. Cancer 1991, 16, 67–72. [Google Scholar] [CrossRef]
- Samarghandian, S.; Azimi-Nezhad, M.; Samini, F. Ameliorative effect of saffron aqueous extract on hyperglycemia, hyperlipidemia, and oxidative stress on diabetic encephalopathy in streptozotocin induced experimental diabetes mellitus. Biomed. Res. Int. 2014, 2014, 920857. [Google Scholar] [CrossRef] [Green Version]
- Ouahhoud, S.; Lahmass, I.; Bouhrim, M.; Khoulati, A.; Sabouni, A.; Benabbes, R.; Asehraou, A.; Choukri, M.; Bnouham, M.; Saalaoui, E. Antidiabetic effect of hydroethanolic extract of Crocus sativus stigmas, tepals and leaves in streptozotocin-induced diabetic rats. Physiol. Pharmacol. 2019, 23, 9–20. [Google Scholar]
- Reyhane, H.; Ahmadreza, S.; Mohadeseh, B.; Masoomeh, V.; Mehran, H. The impact of Crocus sativus stigma against methotrexate-induced liver toxicity in rats. J. Complementary Integr. Med. 2020, 17, 20190201. [Google Scholar]
- Ouahhoud, S.; Touiss, I.; Khoulati, A.; Lahmass, I.; Mamri, S.; Meziane, M.; Elassri, S.; Bencheikh, N.; Benabbas, R.; Asehraou, A. Hepatoprotective effects of hydroethanolic extracts of Crocus sativus tepals, stigmas and leaves on carbon tetrachloride induced acute liver injury in rats. Physiol. Pharmacol. 2021, 25, 178–188. [Google Scholar] [CrossRef]
- Naghizadeh, B.; Boroushaki, M.T.; Vahdati Mashhadian, N.; Mansouri, M.T. Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats. Iran Biomed. J. 2008, 12, 93–100. [Google Scholar] [PubMed]
- Abbasvali, M.; Ranaei, A.; Shekarforoush, S.S.; Moshtaghi, H. The Effects of Aqueous and Alcoholic Saffron (Crocus sativus) Tepal Extracts on Quality and Shelf-Life of Pacific White Shrimp (Litopeneous vannamei) During Iced Storage. J. Food Qual. 2016, 39, 732–742. [Google Scholar] [CrossRef]
- Serrano-Díaz, J.; Sánchez, A.M.; Maggi, L.; Martínez-Tomé, M.; García-Diz, L.; Murcia, M.A.; Alonso, G.L. Increasing the applications of Crocus sativus flowers as natural antioxidants. J. Food Sci. 2012, 77, C1162–C1168. [Google Scholar] [CrossRef] [PubMed]
- Serrano-Díaz, J.; Sánchez, A.M.; Martínez-Tomé, M.; Winterhalter, P.; Alonso, G.L. A contribution to nutritional studies on Crocus sativus flowers and their value as food. J. Food Compos. Anal. 2013, 31, 101–108. [Google Scholar] [CrossRef]
- Zara, S.; Petretto, G.L.; Mannu, A.; Zara, G.; Budroni, M.; Mannazzu, I.; Multineddu, C.; Pintore, G.; Fancello, F. Antimicrobial Activity and Chemical Characterization of a Non-Polar Extract of Saffron Stamens in Food Matrix. Foods 2021, 10, 703. [Google Scholar] [CrossRef]
- Santana-Méridas, O.; González-Coloma, A.; Sánchez-Vioque, R. Agricultural residues as a source of bioactive natural products. Phytochem. Rev. 2012, 11, 447–466. [Google Scholar] [CrossRef]
- Carmona, M.; Sánchez, A.M.; Ferreres, F.; Zalacain, A.; Tomás-Barberán, F.; Alonso, G.L. Identification of the flavonoid fraction in saffron spice by LC/DAD/MS/MS: Comparative Study of Samples from Different Geographical Origins. Food Chem. 2007, 100, 445–450. [Google Scholar] [CrossRef]
- Goupy, P.; Vian, M.A.; Chemat, F.; Caris-Veyrat, C. Identification and quantification of flavonols, anthocyanins and lutein diesters in tepals of Crocus sativus by ultra performance liquid chromatography coupled to diode array and ion trap mass spectrometry detections. Ind. Crops Prod. 2013, 44, 496–510. [Google Scholar] [CrossRef]
- Nørbæk, R.; Kondo, T. Anthocyanins from flowers of Crocus (iridaceae). Phytochemistry 1998, 47, 861–864. [Google Scholar] [CrossRef]
- Smolskaite, L.; Talou, T.; Fabre, N.; Venskutonis, P.R. Volarization of Saffron Industry By-Products: Bioactive Compounds from Leaves; Latvia University of Agriculture, Faculty of Food Technology: Jelgava, Latvia, 2011; pp. 67–72. [Google Scholar]
- Baba, S.A.; Malik, A.H.; Wani, Z.A.; Mohiuddin, T.; Shah, Z.; Abbas, N.; Ashraf, N. Phytochemical analysis and antioxidant activity of different tissue types of Crocus sativus and oxidative stress alleviating potential of saffron extract in plants, bacteria, and yeast. S. Afr. J. Bot. 2015, 99, 80–87. [Google Scholar] [CrossRef]
- Sánchez-Vioque, R.; Santana-Méridas, O.; Polissiou, M.; Vioque, J.; Astraka, K.; Alaiz, M.; Herraiz-Peñalver, D.; Tarantilis, P.A.; Girón-Calle, J. Polyphenol composition and in vitro antiproliferative effect of corm, tepal and leaf from Crocus sativus L. on human colon adenocarcinoma cells (Caco-2). J. Funct. Foods 2016, 24, 18–25. [Google Scholar] [CrossRef] [Green Version]
- Puglia, C.; Santonocito, D.; Musumeci, T.; Cardile, V.; Graziano, A.C.E.; Salerno, L.; Raciti, G.; Crascì, L.; Panico, A.M.; Puglisi, G. Nanotechnological approach to increase the antioxidant and cytotoxic efficacy of crocin and crocetin. Planta Med. 2019, 85, 258–265. [Google Scholar] [CrossRef] [Green Version]
- Xi, L.; Qian, Z.; Xu, G.; Zheng, S.; Sun, S.; Wen, N.; Sheng, L.; Shi, Y.; Zhang, Y. Beneficial impact of crocetin, a carotenoid from saffron, on insulin sensitivity in fructose-fed rats. J. Nutr. Biochem. 2007, 18, 64–72. [Google Scholar] [CrossRef]
- Kyriakoudi, A.; Tsimidou, M.Z.; O’Callaghan, Y.C.; Galvin, K.; O’Brien, N.M. Changes in total and individual crocetin esters upon in vitro gastrointestinal digestion of saffron aqueous extracts. J. Agric. Food Chem. 2013, 61, 5318–5327. [Google Scholar] [CrossRef]
- Moratalla-López, N.; Bagur, M.J.; Lorenzo, C.; Martínez-Navarro, M.E.; Salinas, M.R.; Alonso, G.L. Bioactivity and Bioavailability of the Major Metabolites of Crocus sativus L. Flower. Molecules 2019, 24, 2827. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gutiérrez-Grijalva, E.P.; Ambriz-Pérez, D.L.; Leyva-López, N.; Castillo-López, R.I.; Heredia, J.B. Bioavailability of dietary phenolic compounds. Rev. Española Nutr. Hum. Dietética 2016, 20, 140–147. [Google Scholar] [CrossRef] [Green Version]
- De Vries, J.; Hollman, P.; Meyboom, S.; Buysman, M.; Zock, P.L.; van Staveren, W.A.; Katan, M.B. Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake. Am. J. Clin. Nutr. 1998, 68, 60–65. [Google Scholar] [CrossRef] [Green Version]
- Nielsen, S.E.; Kall, M.; Justesen, U.; Schou, A.; Dragsted, L.O. Human absorption and excretion of flavonoids after broccoli consumption. Cancer Lett. 1997, 114, 173–174. [Google Scholar] [CrossRef]
- DuPont, M.; Day, A.; Bennett, R.; Mellon, F.; Kroon, P. Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans. Eur. J. Clin. Nutr. 2004, 58, 947–954. [Google Scholar] [CrossRef] [Green Version]
- Ng, S.C.; Shi, H.Y.; Hamidi, N.; Underwood, F.E.; Tang, W.; Benchimol, E.I.; Panaccione, R.; Ghosh, S.; Wu, J.C.; Chan, F.K. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A Systematic Review of Population-Based Studies. Lancet 2017, 390, 2769–2778. [Google Scholar] [CrossRef]
- Loftus, P.A.; Wise, S.K. Epidemiology of asthma. Curr. Opin. Otolaryngol. Head Neck Surg. 2016, 24, 245–249. [Google Scholar] [CrossRef]
- Menke, A.; Casagrande, S.; Geiss, L.; Cowie, C.C. Prevalence of and trends in diabetes among adults in the United States, 1988–2012. JAMA 2015, 314, 1021–1029. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schnabel, R.B.; Yin, X.; Gona, P.; Larson, M.G.; Beiser, A.S.; McManus, D.D.; Newton-Cheh, C.; Lubitz, S.A.; Magnani, J.W.; Ellinor, P.T. 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: A Cohort Study. Lancet 2015, 386, 154–162. [Google Scholar] [CrossRef] [Green Version]
- Caughey, G.E.; Roughead, E.E.; Vitry, A.I.; McDermott, R.A.; Shakib, S.; Gilbert, A.L. Comorbidity in the elderly with diabetes: Identification of Areas of Potential Treatment Conflicts. Diabetes Res. Clin. Pract. 2010, 87, 385–393. [Google Scholar] [CrossRef] [PubMed]
- Kartha, G.K.; Li, I.; Comhair, S.; Erzurum, S.C.; Monga, M. Co-occurrence of asthma and nephrolithiasis in children. PLoS ONE 2017, 12, e0168813. [Google Scholar] [CrossRef]
- Gudbjartsson, D.F.; Holm, H.; Indridason, O.S.; Thorleifsson, G.; Edvardsson, V.; Sulem, P.; de Vegt, F.; d’Ancona, F.C.; den Heijer, M.; Franzson, L. Association of variants at UMOD with chronic kidney disease and kidney stones—Role of age and comorbid diseases. PLoS Genet. 2010, 6, e1001039. [Google Scholar] [CrossRef]
- Myers, S.P.; Hawrelak, J. The causes of intestinal dysbiosis: A review. Altern. Med. Rev. 2004, 9, 180–197. [Google Scholar]
- Lynch, S.V.; Pedersen, O. The human intestinal microbiome in health and disease. N. Engl. J. Med. 2016, 375, 2369–2379. [Google Scholar] [CrossRef] [Green Version]
- Blaser, M.J.; Falkow, S. What are the consequences of the disappearing human microbiota? Nat. Rev. Microbiol. 2009, 7, 887–894. [Google Scholar] [CrossRef]
- Hand, T.W.; Vujkovic-Cvijin, I.; Ridaura, V.K.; Belkaid, Y. Linking the microbiota, chronic disease, and the immune system. Trends Endocrinol. Metab. 2016, 27, 831–843. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Deledda, A.; Annunziata, G.; Tenore, G.C.; Palmas, V.; Manzin, A.; Velluzzi, F. Diet-derived antioxidants and their role in inflammation, obesity and gut microbiota modulation. Antioxidants 2021, 10, 708. [Google Scholar] [CrossRef] [PubMed]
- Wali, A.F.; Alchamat, H.A.A.; Hariri, H.K.; Hariri, B.K.; Menezes, G.A.; Zehra, U.; Rehman, M.U.; Ahmad, P. Antioxidant, Antimicrobial, Antidiabetic and Cytotoxic Activity of Crocus sativus L. Petals. Appl. Sci. 2020, 10, 1519. [Google Scholar] [CrossRef] [Green Version]
- Lahmass, I.; Ouahhoud, S.; Elmansuri, M.; Sabouni, A.; Elyoubi, M.; Benabbas, R.; Choukri, M.; Saalaoui, E. Determination of antioxidant properties of six by-products of Crocus sativus L.(saffron) plant products. Waste Biomass Valorization 2018, 9, 1349–1357. [Google Scholar] [CrossRef]
- FDA. CFR—Code of Federal Regulations Title 21. 2017. Available online: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1293 (accessed on 5 May 2022).
- Swain, T.; Hillis, W.E. The phenolic constituents of Prunus domestica. I.—The quantitative analysis of phenolic constituents. J. Sci. Food Agric. 1959, 10, 63–68. [Google Scholar] [CrossRef]
- Sánchez-Moreno, C.; Larrauri, J.A.; Saura-Calixto, F. A procedure to measure the antiradical efficiency of polyphenols. J. Sci. Food Agric. 1998, 76, 270–276. [Google Scholar] [CrossRef]
- Karagözler, A.A.; Erdağ, B.; Emek, Y.; Uygun, D.A. Antioxidant activity and proline content of leaf extracts from Dorystoechas hastata. Food Chem. 2008, 111, 400–407. [Google Scholar] [CrossRef]
- Kabouche, A.; Kabouche, Z.; Öztürk, M.; Kolak, U.; Topçu, G. Antioxidant abietane diterpenoids from Salvia barrelieri. Food Chem. 2007, 102, 1281–1287. [Google Scholar] [CrossRef]
- Carter, P. Spectrophotometric determination of serum iron at the submicrogram level with a new reagent (ferrozine). Anal. Biochem. 1971, 40, 450–458. [Google Scholar] [CrossRef]
- Saiga, A.; Tanabe, S.; Nishimura, T. Antioxidant Activity of Peptides Obtained from Porcine Myofibrillar Proteins by Protease Treatment. J. Agric. Food Chem. 2003, 51, 3661–3667. [Google Scholar] [CrossRef]
- Singh, N.P.; McCoy, M.T.; Tice, R.R.; Schneider, E.L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res. 1988, 175, 184–191. [Google Scholar] [CrossRef] [Green Version]
- Garcia, O.; Romero, I.; González, J.E.; Mandina, T. Measurements of DNA damage on silver stained comets using free Internet software. Mutat. Res. Genet. Toxicol. Environ. Mutagenesis 2007, 627, 186–190. [Google Scholar] [CrossRef] [PubMed]
- Końca, K.; Lankoff, A.; Banasik, A.; Lisowska, H.; Kuszewski, T.; Góźdź, S.; Koza, Z.; Wojcik, A. A cross-platform public domain PC image-analysis program for the comet assay. Mutat. Res. 2003, 534, 15–20. [Google Scholar] [CrossRef]
- Tarantilis, A.P.; Tsoupras, G.; Polissiou, M. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatography-UV-visible photodiode-array detection-mass spectrometry. J. Chromatogr. A 1995, 699, 107–118. [Google Scholar] [CrossRef]
- Shahi, T.; Assadpour, E.; Jafari, S.M. Main chemical compounds and pharmacological activities of stigmas and tepals of ‘red gold’; saffron. Trends Food Sci. Technol. 2016, 58, 69–78. [Google Scholar] [CrossRef]
- Zeka, K.; Ruparelia, K.C.; Continenza, M.A.; Stagos, D.; Vegliò, F.; Arroo, R.R. Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol. Fitoterapia 2015, 107, 128–134. [Google Scholar] [CrossRef]
- Lautenschläger, M.; Sendker, J.; Hüwel, S.; Galla, H.; Brandt, S.; Düfer, M.; Riehemann, K.; Hensel, A. Intestinal formation of trans-crocetin from saffron extract (Crocus sativus L.) and in vitro permeation through intestinal and blood brain barrier. Phytomedicine 2015, 22, 36–44. [Google Scholar] [CrossRef]
- Asai, A.; Nakano, T.; Takahashi, M.; Nagao, A. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J. Agric. Food Chem. 2005, 53, 7302–7306. [Google Scholar] [CrossRef]
- Umigai, N.; Murakami, K.; Ulit, M.; Antonio, L.; Shirotori, M.; Morikawa, H.; Nakano, T. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration. Phytomedicine 2011, 18, 575–578. [Google Scholar] [CrossRef]
- Manach, C. and J.L. Donovan, Pharmacokinetics and metabolism of dietary flavonoids in humans. Free. Radic. Res. 2004, 38, 771–786. [Google Scholar] [CrossRef]
- Colombo, M.; de Lima Melchiades, G.; Michels, L.R.; Figueiró, F.; Bassani, V.L.; Teixeira, H.F.; Koester, L.S. Solid dispersion of kaempferol: Formulation development, characterization, and oral bioavailability assessment. AAPS PharmSciTech 2019, 20, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Direito, R.; Rocha, J.; Sepodes, B.; Eduardo-Figueira, M. Phenolic compounds impact on rheumatoid arthritis, inflammatory bowel disease and microbiota modulation. Pharmaceutics 2021, 13, 145. [Google Scholar] [CrossRef] [PubMed]
- Tomás-Barberán, F.A.; Selma, M.V.; Espín, J.C. Interactions of gut microbiota with dietary polyphenols and consequences to human health. Curr. Opin. Clin. Nutr. Metab. Care 2016, 19, 471–476. [Google Scholar] [CrossRef]
- Lamousé-Smith, E.S.; Tzeng, A.; Starnbach, M.N. The intestinal flora is required to support antibody responses to systemic immunization in infant and germ free mice. PLoS ONE 2011, 6, e27662. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Round, L.J.; Mazmanian, S.K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 2009, 9, 313–323. [Google Scholar] [CrossRef] [PubMed]
- Round, J.L.; Lee, S.M.; Li, J.; Tran, G.; Jabri, B.; Chatila, T.A.; Mazmanian, S.K. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 2011, 332, 974–977. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spor, A.; Koren, O.; Ley, R. Unravelling the effects of the environment and host genotype on the gut microbiome. Nat. Rev. Microbiol. 2011, 9, 279–290. [Google Scholar] [CrossRef]
- Brown, L.M. Helicobacter pylori: Epidemiology and routes of transmission. Epidemiol. Rev. 2000, 22, 283–297. [Google Scholar] [CrossRef]
- Etxeberria, U.; Arias, N.; Boqué, N.; Macarulla, M.T.; Portillo, M.P.; Martínez, J.A.; Milagro, F.I. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J. Nutr. Biochem. 2015, 26, 651–660. [Google Scholar] [CrossRef]
- Hidalgo, M.; Oruna-Concha, M.J.; Kolida, S.; Walton, G.E.; Kallithraka, S.; Spencer, J.P.; de Pascual-Teresa, S. Metabolism of anthocyanins by human gut microflora and their influence on gut bacterial growth. J. Agric. Food Chem. 2012, 60, 3882–3890. [Google Scholar] [CrossRef]
- Kawabata, K.; Sugiyama, Y.; Sakano, T.; Ohigashi, H. Flavonols enhanced production of anti-inflammatory substance (s) by Bifidobacterium adolescentis: Prebiotic actions of galangin, quercetin, and fisetin. Biofactors 2013, 39, 422–429. [Google Scholar] [CrossRef] [PubMed]
- Parkar, G.S.; Stevenson, D.E.; Skinner, M.A. The potential influence of fruit polyphenols on colonic microflora and human gut health. Int. J. Food Microbiol. 2008, 124, 295–298. [Google Scholar] [CrossRef] [PubMed]
- He, J.; Giusti, M.M. Anthocyanins: Natural Colorants with Health-Promoting Properties. Annu. Rev. Food Sci. Technol. 2010, 1, 163–187. [Google Scholar] [CrossRef] [PubMed]
- Forester, C.S.; Waterhouse, A.L. Gut metabolites of anthocyanins, gallic acid, 3-O-methylgallic acid, and 2,4,6-trihydroxybenzaldehyde, inhibit cell proliferation of Caco-2 cells. J. Agric. Food Chem. 2010, 58, 5320–5327. [Google Scholar] [CrossRef]
- Norberto, S.; Silva, S.; Meireles, M.; Faria, A.; Pintado, M.; Calhau, C. Blueberry anthocyanins in health promotion: A metabolic overview. J. Funct. Foods 2013, 5, 1518–1528. [Google Scholar] [CrossRef]
- Zhang, X.; Yang, Y.; Wu, Z.; Weng, P. The modulatory effect of anthocyanins from purple sweet potato on human intestinal microbiota in vitro. J. Agric. Food Chem. 2016, 64, 2582–2590. [Google Scholar] [CrossRef]
- Fernandez-Prado, R.; Esteras, R.; Perez-Gomez, M.V.; Gracia-Iguacel, C.; Gonzalez-Parra, E.; Sanz, A.B.; Ortiz, A.; Sanchez-Niño, M.D. Nutrients turned into toxins: Microbiota modulation of nutrient properties in chronic kidney disease. Nutrients 2017, 9, 489. [Google Scholar] [CrossRef] [Green Version]
- Fenga, C. Gut microbiota modulation: A Tailored Approach for the Prevention of Chronic Diseases. Biomed. Rep. 2022, 16, 1–2. [Google Scholar] [CrossRef]
- Katalinic, V.; Milos, M.; Kulisic, T.; Jukic, M. Screening of 70 medicinal plant extracts for antioxidant capacity and total phenols. Food Chem. 2006, 94, 550–557. [Google Scholar] [CrossRef]
- Ghedadba, N.; Bousselsela, H.; Hambaba, L.; Benbia, S.; Mouloud, Y. Évaluation de l’activité antioxydante et antimicrobienne des feuilles et des sommités fleuries de Marrubium vulgare L. Phytothérapie 2014, 12, 15–24. [Google Scholar] [CrossRef]
- Mir, M.A.; Rameashkannan, M.; Pala, R.A. Screening of Crocus sativus L. (Saffron) Bio-residues from kashmir as a source of phenols and flavonoids with antioxidant potential. Adv. Biotechnol. Pat. 2014, 303. [Google Scholar]
- Siddhuraju, P. and K. Becker, The antioxidant and free radical scavenging activities of processed cowpea (Vigna unguiculata (L.) Walp.) seed extracts. Food Chem. 2007, 101, 10–19. [Google Scholar] [CrossRef]
- Kumaran, A.; Karunakaran, R.J. In vitro antioxidant activities of methanol extracts of five Phyllanthus species from India. LWT-Food Sci. Technol. 2007, 40, 344–352. [Google Scholar] [CrossRef]
- Jeong, S.-M.; Kim, S.-Y.; Kim, D.-R.; Jo, S.-C.; Nam, K.; Ahn, D.; Lee, S.-C. Effect of heat treatment on the antioxidant activity of extracts from citrus peels. J. Agric. Food Chem. 2004, 52, 3389–3393. [Google Scholar] [CrossRef] [PubMed]
- Sánchez-Vioque, R.; Rodríguez-Conde, M.; Reina-Urena, J.; Escolano-Tercero, M.; Herraiz-Peñalver, D.; Santana-Méridas, O. In vitro antioxidant and metal chelating properties of corm, tepal and leaf from saffron (Crocus sativus L.). Ind. Crops Prod. 2012, 39, 149–153. [Google Scholar] [CrossRef]
- Gadow, V.A.; Joubert, E.; Hansmann, C.F. Comparison of the antioxidant activity of aspalathin with that of other plant phenols of rooibos tea (Aspalathus linearis), α-tocopherol, BHT, and BHA. J. Agric. Food Chem. 1997, 45, 632–638. [Google Scholar] [CrossRef]
- Moure, A.; Franco, D.; Sineiro, J.; Domínguez, H.; Núñez, M.J.; Lema, J.M. Evaluation of extracts from Gevuina avellana hulls as antioxidants. J. Agric. Food Chem. 2000, 48, 3890–3897. [Google Scholar] [CrossRef]
- Koleva, I.I.; Van Beek, T.A.; Linssen, J.P.; Groot, A.D.; Evstatieva, L.N. Screening of plant extracts for antioxidant activity: A comparative study on three testing methods. Phytochem. Anal. Int. J. Plant Chem. Biochem. Tech. 2002, 13, 8–17. [Google Scholar] [CrossRef]
- Pathirana, L.M.C.; Shahidi, F. Antioxidant properties of commercial soft and hard winter wheats (Triticum aestivum L.) and their milling fractions. J. Sci. Food Agric. 2006, 86, 477–485. [Google Scholar] [CrossRef]
- Gülçın, İ.; Oktay, M.; Kıreçcı, E.; Küfrevıoǧlu, Ö.İ. Screening of antioxidant and antimicrobial activities of anise (Pimpinella anisum L.) seed extracts. Food Chem. 2003, 83, 371–382. [Google Scholar] [CrossRef]
- Jomova, K.; Valko, M. Advances in metal-induced oxidative stress and human disease. Toxicology 2011, 283, 65–87. [Google Scholar] [CrossRef] [PubMed]
- Yen, G.; Chen, H.; Peng, H. Evaluation of the cytotoxicity, mutagenicity and antimutagenicity of emerging edible plants. Food Chem. Toxicol. 2001, 39, 1045–1053. [Google Scholar] [CrossRef]
- Hosseinzadeh, H.; Sadeghnia, H.R. Effect of safranal, a constituent of Crocus sativus (Saffron), on methyl methanesulfonate (MMS)–induced DNA damage in mouse organs: An Alkaline Single-Cell Gel Electrophoresis (Comet) Assay. DNA Cell Biol. 2007, 26, 841–846. [Google Scholar] [CrossRef] [PubMed]
- Fairbairn, D.W.; Olive, P.L.; O’Neill, K.L. The comet assay: A comprehensive review. Mutat. Res. /Rev. Genet. Toxicol. 1995, 339, 37–59. [Google Scholar] [CrossRef]
- Tice, R.; Andrews, P.; Hirai, O.; Singh, N. The Single Cell Gel (SCG) Assay: An Electrophoretic Technique for the Detection of DNA Damage in Individual Cells, in Biological Reactive Intermediates IV; Springer: Boston, MA, USA, 1991; pp. 157–164. [Google Scholar]
- Tice, R. The single cell gel/comet assay: A Microgel Electrophoretic Technique for the Detection of DNA Damage and Repair in Individual Cells. Environ. Mutagenesis 1995, 2, 315–339. [Google Scholar]
- Abdullaev, F.; Riveron-Negrete, L.; Caballero-Ortega, H.; Hernández, J.M.; Perez-Lopez, I.; Pereda-Miranda, R.; Espinosa-Aguirre, J. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicol. In Vitro 2003, 17, 731–736. [Google Scholar] [CrossRef]
- Caballero-Ortega, H.; Riverón-Negrete, L.; Pereda-Miranda, R.; Rivera-Luna, R.; Hernández, M.; Pérez-López, I.; Espinosa-Aguirre, J. In vitro evaluation of the chemopreventive potential of saffron. Rev. Investig. Clin. Organo Hosp. Enferm. Nutr. 2002, 54, 430–436. [Google Scholar]
- Hosseinzadeh, H.; Abootorabi, A.; Sadeghnia, H.R. Protective effect of Crocus sativus stigma extract and crocin (trans-crocin 4) on methyl methanesulfonate–induced DNA damage in mice organs. DNA Cell Biol. 2008, 27, 657–664. [Google Scholar] [CrossRef] [Green Version]
- Premkumar, K.; Thirunavukkarasu, C.; Abraham, S.; Santhiya, S.; Ramesh, A. Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice. Hum. Exp. Toxicol. 2006, 25, 79–84. [Google Scholar] [CrossRef]
- Salomi, M.; Nair, S.; Panikkar, K. Cytotoxicity and non-mutagenicity of Nigela sativa and saffron (Crocus sativus) in vitro. Proc. Ker. Sci. Congr. 1991, 5, 244. [Google Scholar]
- Cohen, G.; Heikkila, R.E. The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6-hydroxydopamine, dialuric acid, and related cytotoxic agents. J. Biol. Chem. 1974, 249, 2447–2452. [Google Scholar] [CrossRef]
- Winterbourn, C.C.; Munday, R. Glutathione-mediated redox cycling of alloxan: Mechanisms of superoxide dismutase inhibition and of metal-catalyzed OH formation. Biochem. Pharmacol. 1989, 38, 271–277. [Google Scholar] [CrossRef]
- Munday, R. Dialuric acid autoxidation: Effects of transition metals on the reaction rate and on the generation of “active oxygen” species. Biochem. Pharmacol. 1988, 37, 409–413. [Google Scholar] [CrossRef]
- Delaney, C.A.; Dunger, A.; Di Matteo, M.; Cunningham, J.M.; Green, M.H.; Green, I.C. Comparison of inhibition of glucose-stimulated insulin secretion in rat islets of Langerhans by streptozotocin and methyl and ethyl nitrosoureas and methanesulphonates: Lack of correlation with nitric oxide-releasing or O6-alkylating ability. Biochem. Pharmacol. 1995, 50, 2015–2020. [Google Scholar] [CrossRef]
- Elsner, M.; Guldbakke, B.; Tiedge, M.; Munday, R.; Lenzen, S. Relative importance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin. Diabetologia 2000, 43, 1528–1533. [Google Scholar] [CrossRef] [Green Version]
- Sandler, S.; Swenne, I. Streptozotocin, but not alloxan, induces DNA repair synthesis in mouse pancreatic islets in vitro. Diabetologia 1983, 25, 444–447. [Google Scholar] [CrossRef] [Green Version]
- Heller, B.; Bürkle, A.; Radons, J.; Fengler, E.; Jalowy, A.; Müller, M.; Burkart, V.; Kolb, H. Analysis of oxygen radical toxicity in pancreatic islets at the single cell level. Biol. Chem. 1994, 375, 597–602. [Google Scholar] [CrossRef]
- Turk, J.; Corbett, J.A.; Ramanadham, S.; Bohrer, A.; McDaniel, M.L. Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochem. Biophys. Res. Commun. 1993, 197, 1458–1464. [Google Scholar] [CrossRef]
- Kröncke, K.-D.; Fehsel, K.; Sommer, A.; Rodriguez, M.-L.; Kolb-Bachofen, V. Nitric oxide generation during cellular metabolization of the diabetogenic N-Mefhyl-N-Nitroso-Urea streptozotozin contributes to islet cell DNA damage. Biol. Chem. 1995, 376, 179–186. [Google Scholar] [CrossRef]
- Katsumata, K.; Katsumata, Y. Protective effect of diltiazem hydrochloride on the occurrence of alloxan-or streptozotocin-induced diabetes in rats. Horm. Metab. Res. 1992, 24, 508–510. [Google Scholar] [CrossRef]
- Karuna, R.; Reddy, S.S.; Baskar, R.; Saralakumari, D. Antioxidant potential of aqueous extract of Phyllanthus amarus in rats. Indian J. Pharmacol. 2009, 41, 64–67. [Google Scholar] [PubMed] [Green Version]
- Kraynak, A.; Storer, R.; Jensen, R.; Kloss, M.; Soper, K.; Clair, J.; DeLuca, J.; Nichols, W.; Eydelloth, R. Extent and persistence of streptozotocin-induced DNA damage and cell proliferation in rat kidney as determined by in vivo alkaline elution and BrdUrd labeling assays. Toxicol. Appl. Pharmacol. 1995, 135, 279–286. [Google Scholar] [CrossRef] [PubMed]
- Schmezer, P.; Eckert, C.; Liegibel, U.M. Tissue-specific induction of mutations by streptozotocin in vivo. Mutat. Res. Fundam. Mol. Mech. Mutagenesis 1994, 307, 495–499. [Google Scholar] [CrossRef]
- Park, K.S.; Kim, J.H.; Kim, M.S.; Kim, J.M.; Kim, S.K.; Choi, J.Y.; Chung, M.H.; Han, B.; Kim, S.Y.; Lee, H.K. Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats. Diabetes 2001, 50, 2837–2841. [Google Scholar] [CrossRef] [Green Version]
- Ramon, O.; Wong, H.-K.; Joyeux, M.; Riondel, J.; Halimi, S.; Ravanat, J.-L.; Favier, A.; Cadet, J. 2′-deoxyguanosine oxidation is associated with decrease in the DNA-binding activity of the transcription factor Sp1 in liver and kidney from diabetic and insulin-resistant rats. Free. Radic. Biol. Med. 2001, 30, 107–118. [Google Scholar] [CrossRef]
- Blasiak, J.; Sikora, A.; Czechowska, A.; Drzewoski, J. Free radical scavengers can modulate the DNA-damaging action of alloxan. Acta Biochim. Pol. 2003, 50, 205–210. [Google Scholar] [CrossRef]
- Alam, M.M.; Meerza, D.; Naseem, I. Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage in alloxan induced type 2 diabetic mice. Life Sci. 2014, 109, 8–14. [Google Scholar] [CrossRef]
- Etuk, E. Animals models for studying diabetes mellitus. Agric. Biol. JN Am. 2010, 1, 130–134. [Google Scholar]
- Premkumar, K.; Abraham, S.K.; Santhiya, S.T.; Ramesh, A. Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother. Res. 2003, 17, 614–617. [Google Scholar] [CrossRef]
- Tseng, T.-H.; Chu, C.-Y.; Huang, J.-M.; Shiow, S.-J.; Wang, C.-J. Crocetin protects against oxidative damage in rat primary hepatocytes. Cancer Lett. 1995, 97, 61–67. [Google Scholar] [CrossRef]
- Niering, P.; Michels, G.; Wätjen, W.; Ohler, S.; Steffan, B.; Chovolou, Y.; Kampkötter, A.; Proksch, P.; Kahl, R. Protective and detrimental effects of kaempferol in rat H4IIE cells: Implication of oxidative stress and apoptosis. Toxicol. Appl. Pharmacol. 2005, 209, 114–122. [Google Scholar] [CrossRef] [PubMed]
- Anderson, D.; Dobryńska, M.M.; Başaran, N.; Başaran, A.; Yu, T.W. Flavonoids modulate Comet assay responses to food mutagens in human lymphocytes and sperm. Mutat. Res. Fundam. Mol. Mech. Mutagenesis 1998, 402, 269–277. [Google Scholar] [CrossRef]
- Ramos, A.A.; Lima, C.F.; Pereira, M.L.; Fernandes-Ferreira, M.; Pereira-Wilson, C. Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells: Evaluation by the comet assay. Toxicol. Lett. 2008, 177, 66–73. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- García Forero, A.; Villamizar Mantilla, D.A.; Núñez, L.A.; Ocazionez, R.E.; Stashenko, E.E.; Fuentes, J.L. Photoprotective and Antigenotoxic Effects of the Flavonoids Apigenin, Naringenin and Pinocembrin. Photochem. Photobiol. 2019, 95, 1010–1018. [Google Scholar] [CrossRef] [PubMed]
- Llópiz, N.; Puiggròs, F.; Céspedes, E.; Arola, L.; Ardévol, A.; Bladé, C.; Salvadó, M.J. Antigenotoxic Effect of Grape Seed Procyanidin Extract in Fao Cells Submitted to Oxidative Stress. J. Agric. Food Chem. 2004, 52, 1083–1087. [Google Scholar] [CrossRef]
Sample | Polyphenol Content (µg GA eq/mg Extract) |
---|---|
STG | (34.41 ± 1.09) |
TPL | (64.66 ± 0.20) |
LV | (38.56 ± 0.34) |
Sample | IC50 (µg/mL) |
---|---|
STG | 1554.37 ± 299.09 |
TPL | 80.73 ± 0.71 |
LV | 101.50 ± 1.55 |
Asc.A | 2.50 ± 0.20 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ouahhoud, S.; Khoulati, A.; Kadda, S.; Bencheikh, N.; Mamri, S.; Ziani, A.; Baddaoui, S.; Eddabbeh, F.-E.; Lahmass, I.; Benabbes, R.; et al. Antioxidant Activity, Metal Chelating Ability and DNA Protective Effect of the Hydroethanolic Extracts of Crocus sativus Stigmas, Tepals and Leaves. Antioxidants 2022, 11, 932. https://doi.org/10.3390/antiox11050932
Ouahhoud S, Khoulati A, Kadda S, Bencheikh N, Mamri S, Ziani A, Baddaoui S, Eddabbeh F-E, Lahmass I, Benabbes R, et al. Antioxidant Activity, Metal Chelating Ability and DNA Protective Effect of the Hydroethanolic Extracts of Crocus sativus Stigmas, Tepals and Leaves. Antioxidants. 2022; 11(5):932. https://doi.org/10.3390/antiox11050932
Chicago/Turabian StyleOuahhoud, Sabir, Amine Khoulati, Salma Kadda, Noureddine Bencheikh, Samira Mamri, Anas Ziani, Sanae Baddaoui, Fatima-Ezzahra Eddabbeh, Iliass Lahmass, Redouane Benabbes, and et al. 2022. "Antioxidant Activity, Metal Chelating Ability and DNA Protective Effect of the Hydroethanolic Extracts of Crocus sativus Stigmas, Tepals and Leaves" Antioxidants 11, no. 5: 932. https://doi.org/10.3390/antiox11050932