Pomegranate Juice Improves Iron Status and Ameliorates Iron Deficiency Induced Cellular Changes in Saccharomyces cerevisiae
DOI:
https://doi.org/10.6000/1929-5634.2015.04.03.5Keywords:
Iron deficiency anemia, Ayurveda, Pandu, Pomegranate, Rasayana, S. cerevisiaeAbstract
Background: Iron Deficiency Anemia (IDA) is most prevalent form of anemia affecting around 2 billion people world-wide. Ayurveda, an Indian system of medicine, describes pomegranate (Punica granatum) fruits as a Rasayana and a dietary supplement for managing a condition called Pandu, which is akin to IDA. Rasayanas are methods to maintain homeostasis by improving digestion, metabolism and absorption of nutrients and elimination of waste. Yeast (Saccharomyces cerevisiae) has been a well-accepted model organism to study iron metabolism.
Materials & Methods: In the current study we developed ‘anemic yeast’ by culturing yeast cells in iron-free medium with bathophenanthroline disulfonate (BPS). The effect of pomegranate juice (PJ) on reversing the ‘IDA like’ condition in yeast was studied.
Results: Culturing iron deficient (ID) cells in the presence of 10% PJ supplemented medium (IDP), improved iron status by at least 7 fold (p<0.0001) and reversed mitochondrial degeneration induced by iron deficiency. Percentage of healthy reticulate mitochondria in IDP cells was >30% higher (p<0.0001) than that in the ID cells grown in iron deficient medium (IDD) and at least 14% more than that in ID cells grown in 10% PJ-equivalent iron substituted media. Interestingly, PJ substitution improved the functional ferrous (Fe2+) form as well as the bio-assimilated heme form of iron, but not the ferric (Fe3+) storage form in ID cells.
Conclusion: Yeast model can be useful as a quick screen to identify potential nutritional supplements. Pomegranate’s potential role as a nutritional supplement in IDA management and as a hematinic is worthy of further research
References
Munoz M, Villar I, Garcia-Erce JA. An update on iron physiology. World J Gastroenterol 2009; 15: 4617-26. http://dx.doi.org/10.3748/wjg.15.4617
Formanowicz D, Formanowicz P. An overall view of the process of the regulation of human iron metabolism. Journal of Biotechnology, Computational Biology and Bionanotechnology 2011; 92: 193-207. http://dx.doi.org/10.5114/bta.2011.46534
McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anemia, WHO Vitamins and Mineral Nutrition Information System, 1993 – 2005. Public Health Nutrition 2009; 12: 444-54. http://dx.doi.org/10.1017/S1368980008002401
Lesuisse E, Raguzzi F, Crichton RR. Iron uptake by the yeast Saccharomyces cerevisiae: involvement of a reduction step. J Gen Microbiol 1987; 133: 3229-36. http://dx.doi.org/10.1099/00221287-133-11-3229
Balarajan Y, Ramakrishnan U, Ozaltin E, Shankar AH, Subramanian SV. Anemia in low-income and middle-income countries. Lancet 2011; 378: 2123-35. http://dx.doi.org/10.1016/S0140-6736(10)62304-5
Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron deficiency anaemia. The Lancet 2015; pii: S0140-6736: 60865-70. http://dx.doi.org/10.1016/S0140-6736(15)60865-0
Shah M, Griffin IJ, Lifschitz CH, Abrams SA. Effect of orange and apple juices on iron absorption in children. Arch Pediatr Adolesc Med 2003; 157: 1232-36. http://dx.doi.org/10.1001/archpedi.157.12.1232
Nair KM, Brahmam GN, Radhika MS, Dripta RC, Ravinder P, Balakrishna N, Chen Z, Hawthorne KM, Abrams SA. Inclusion of guava enhances non-heme iron bioavailability but not fractional zinc absorption from a rice-based meal in adolescents. J Nutr 2013; 143: 852-8. http://dx.doi.org/10.3945/jn.112.171702
Venkatasubramanian P, Koul IB, Varghese RK, Koyyala S, Shivakumar A. Amla (Phyllanthus emblica L.) enhances iron dialysability and uptake in in-vitro models. Current Science 2014; 107: 1859-66.
Rao S. Potential of community based approach for prevention of anaemia among women of child bearing age from rural India. Journal of Food and Nutrition Sciences 2014; 2: 270-6. http://dx.doi.org/10.11648/j.jfns.20140206.15
Murthy KRS, Ed. Astanga Samgraha of Vagbhata (Sarira, Nidana, Cikitsita and Kalpa Sthana) (Vol II). Varanasi: Chakhambha Orientalia 2009.
Chunekar KC, Ed. Bhavaprakasha Nighantu. Varanasi: Chaukhambha Bharati Academy 2004.
Udapa MH. Comprehensive Kaayachikitsa and Principles of Ayurveda. Bangalore: Laveena Publications 2004.
Balasubramani SP, Venkatasubramanian P, Kukkupuni SK, Patwardhan B. Plant-based Rasayana drugs from Ayurveda. Chin J Integr Med 2011; 17: 88-94. http://dx.doi.org/10.1007/s11655-011-0659-5
Wang R, Ding Y, Liu R, Xiang L, Du L. Pomegranate: constituents, bioactivities and pharmacokinetics. Fruits Veg Cereal Sci Biotech 2010; 4(Spl issue 2): 77-87.
Viladomiu M, Hontecillas R, Lu P, Bassaganya-Riera J. Preventive and prophylactic mechanisms of action of pomegranate bioactive constituents. Evidence-Based Complementary and Alternative Medicine 2013. http://dx.doi.org/10.1155/2013/789764
Faria A, Calhau C. The bioactivity of pomegranate: impact on health and disease. Crit Rev Food SciNutr 2011; 51: 626-34. http://dx.doi.org/10.1080/10408391003748100
Medjakovic S, Jungbauer A. Pomegranate: a fruit that ameliorates metabolic syndrome. Food Funct 2013; 4: 19-39. http://dx.doi.org/10.1039/c2fo30034f
Balasubramani SP, Mohan J, Esha P, Arunita C, Kumar KS, Nongthomba U, Venkatasubramanian P. Pomegranate juice enhances healthy lifespan in Drosophila melanogaster. Front Public Health 2014; 2: 245. http://dx.doi.org/10.3389/fpubh.2014.00245
Garcia Y, Diaz-Castro J. Advantages and disadvantages of the animal models v. in vitro studies in iron metabolism: a review. Animal 2013; 7: 1651-8. http://dx.doi.org/10.1017/S1751731113001134
De Freitas J, Wintz H, Kim JH, Poynton H, Fox T, Vulpe C. Yeast, a model organism for iron and copper metabolism studies. Biometals 2003; 16: 185-97. http://dx.doi.org/10.1023/A:1020771000746
Yun CW, Ferea T, Rashford J, Ardon O, Brown PO, Botstein D, Kaplan J, Philpott CC. Desferrioxamine-mediated iron uptake in Saccharomyces cerevisiae. Evidence for two pathways of iron uptake. J Biol Chem 2000; 275: 10709-15. http://dx.doi.org/10.1074/jbc.275.14.10709
Minear S, O'Donnell AF, Ballew A, Giaever G, Nislow C, Stearns T, Cyert MS. Curcumin inhibits growth of Saccharomyces cerevisiae through iron chelation. Eukaryot Cell 2011; 10: 1574-81. http://dx.doi.org/10.1128/EC.05163-11
Huang Z, Chen K, Xu T, Zhang J, Li Y, Li W, Agarwal AK, Clark AM, Phillips JD, Pan X Sampangine inhibits heme biosynthesis in both yeast and human. Eukaryot Cell 2011; 10: 1536-44. http://dx.doi.org/10.1128/EC.05170-11
Jo WJ, Kim JH, Oh E, Jaramillo D, Holman P, Loguinov AV, Arkin AP, Nislow C, Giaever G, Vulpe CD. Novel insights into iron metabolism by integrating deletome and transcriptome analysis in an iron deficiency model of the yeast Saccharomyces cerevisiae. BMC Genomics 2009; 10: 130. http://dx.doi.org/10.1186/1471-2164-10-130
Shakoury-Elizeh M, Protchenko O, Berger A, Cox J, Gable K, Dunn TM, Prinz WA, Bard M, Philpott CC. Metabolic response to iron deficiency in Saccharomyces cerevisiae. J Biol Chem 2010; 285: 14823-33. http://dx.doi.org/10.1074/jbc.M109.091710
Forner J, Binder S. The red fluorescent protein eqFP611: application in sub-cellular localization studies in higher plants. BMC Plant Biol 2007; 7: 28. http://dx.doi.org/10.1186/1471-2229-7-28
Folch J, Lees M, Stanley Gh S. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957; 226: 497-509.
Seo AY, Joseph AM, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C. New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci 2010; 123: 2533-42. http://dx.doi.org/10.1155/2014/210934
WHO. The global prevalence of anaemia in 2011. Geneva: World Health Organization 2015.
Sharma PV, Ed. Caraka-Samhita, Vol II. Varanasi: Chaukhambha Orientalia 2001.
Philpott CC, Protchenko O. Response to iron deprivation in Saccharomyces cerevisiae. Eukaryot Cell 2008; 7: 20-7. http://dx.doi.org/10.1128/EC.00354-07
Raguzzi F, Lesuisse E, Crichton RR. Iron storage in Saccharomyces cerevisiae. FEBS Letters 1988; 231: 253-8. http://dx.doi.org/10.1016/0014-5793(88)80742-7
Holmes-Hampton GP, Jhurry ND, McCormick SP, Lindahl PA. Iron content of Saccharomyces cerevisiae cells grown under iron-deficient and iron-overload conditions. Biochemistry 2013; 52: 105-14. http://dx.doi.org/10.1021/bi3015339
Walter PB, Knutson MD, Paler-Martinez A, Lee S, Xu Y, Viteri FE, Ames BN. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Natl Acad Sci USA 2002; 99: 2264-69. http://dx.doi.org/10.1073/pnas.261708798
Okamoto K, Shaw JM. Mitochondrial morphology and dynamics in yeast and multicellular eukaryotes. Annu Rev Genet 2005. 39: 503-36.
http://.dx.doi.org/10.1146/annurev.genet.38.072902.093019
Bossy-Wetzel E, Barsoum MJ, Godzik A, Schwarzenbacher R, Lipton SA. Mitochondrial fission in apoptosis, neurodegeneration and aging. Curr Opin Cell Biol 2003; 15: 706-16. http://dx.doi.org/10.1016/j.ceb.2003.10.015
Puig S, Askeland E, Thiele DJ. Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation. Cell 2005; 120: 99-110. http://dx.doi.org/10.1016/j.cell.2004.11.032
Ihrig J, Hausmann A, Hain A, Richter N, Hamza I, Lill R, Muhlenhoff U. Iron regulation through the back door: iron-dependent metabolite levels contribute to transcriptional adaptation to iron deprivation in Saccharomyces cerevisiae. Eukaryot Cell 2010; 9: 460-71. http://dx.doi.org/10.1128/EC.00213-09
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