An Overview on Genistein and its Various Formulations

Neha Jaiswal; Juber Akhtar; Satya Prakash Singh; Farogh Ahsan; Badruddeen

doi:10.1055/a-0797-3657

Drug Research, Table of Contents

Drug Res (Stuttg) 2019; 69(06): 305-313
DOI: 10.1055/a-0797-3657

Review

An Overview on Genistein and its Various Formulations

Neha Jaiswal

¹Department of Pharmaceutics, Integral University, Lucknow, India

,

Juber Akhtar

¹Department of Pharmaceutics, Integral University, Lucknow, India

,

Satya Prakash Singh

¹Department of Pharmaceutics, Integral University, Lucknow, India

,

Badruddeen,

Farogh Ahsan

²Department of Pharmacology, Integral University, Lucknow, Inidia

› Author Affiliations

Abstract

Genistein is the natural isoflavone and a phytoestrogen with a broad range of pharmacological properties, such as tyrosine and topoisomerase inhibition. It also induces apoptosis and cell proliferation inhibition, differentiates cancer cells. Added health benefits include the reduction of osteoporosis by suppressing osteoclasts and lymphocyte functions, decreased the risk of cardiovascular attacks and relieved postmenopausal problems. Genistein traditionally used in Chinese and Ayurvedic medicine and are found to be associated with lower risk of breast, prostate and lung cancer. Numerous factors comprising genetic, epigenetic and transcriptomic alterations are evidenced to be responsible for breast, prostate and lung cancer. In present review, an overview on genistein, the various analytical methods and drug delivery approaches to determine genistein in the formulations are discussed. It may help to develop novel formulations with better solubility and bioavailability of genistein. The tumor cell scan may be targeted to form a stable genistein formulation.

Key words

apoptosis - breast cancer - genistein - nanoformulations

Full Text

References

References
1 Ganai AA, Farooqi H. Bioactivity of genistein: A review of in vitro and in vivo studies. Biomedicine & Pharmacotherapy 2015; 76: 30-38
2 Bhagwat S, Haytowitz DB, Holden JM. USDA database for the isoflavone content of selected foods. Release 2.0. Bethesda (MD): USDA; 2008
3 Messina M, Nagata C, Anna HW. Estimated Asian Adult Soy Protein and Isoflavone Intakes. Nutrition and Cancer 2006; 55: 1-12
4 Van Erp-Baart MA, Brants HA, Kiely M. et al. Isoflavone intake in four different European countries: The venus approach. Br J Nutr 2003; 89: S25-S30
5 Liggins J, Bluck L, Runswick S. et al. Daidzein and genistein contents of vegetables. Br J Nutr 2000; 84: 717-725
6 Liggins J, Bluck LJ, Runswick S. et al. Daidzein and genistein content of fruits and nuts. J Nutr Biochem 2000; 11: 326-331
7 Ahmad S, Pathak D. Nutritional changes in soybean during germination. J Food SciTechnol 2000; 37: 665-666
8 Kim WJ, Lee HY, Won MH. et al. Germination effect of soybean on its contents of isoflavones and oligosaccharides. Food Sci Biotechnol 2005; 14: 498-502
9 Quinhone Jr. A, Ida E. Profile of the contents of different forms of soybean isoflavones and the effect of germination time on these compounds and the physical parameters in soybean sprouts. Food Chem 2015; 166: 173-178
10 Lee SY, Lee S, Lee S. et al. Primary andsecondary metabolite profiling of doenjang, a fermented soybean pasteduring industrial processing. Food Chem 2014; 165: 157-166
11 Sohn SI, Kim YH, Kim SL. et al. Genistein production in rice seed via transformation with soybean IFSgenes. Plant Sci 2014; 217–218: 27-35
12 Markovits J, Linassier C, Fosse P. et al. Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. Cancer Res 1989; 49: 5111-5117
13 Cassidy A. Potential tissue selectivity of dietary phytoestrogens and estrogens. Curr Opin Lipidol 1999; 10: 47-52
14 Tham DM, Gardner CD, Haskell WL. Clinical review 97: Potential health benefits of dietary phytoestrogens: A review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 1998; 83: 2223-2235
15 Farina HG, Pomies M, Alonso DF. et al. Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncology Reports 2006; 16: 885-891
16 Barnes S, Kim H, Usmar VD. et al. Beyond ERα and ERβ: Estrogen receptor binding is only part of the isoflavone story. The Journal of Nutrition 2000; 130: 656S-657S
17 Dixon RA, Ferreira D. Molecules of interest genistein. Phytochemistry 2002; 60: 205-211
18 Magee PJ, Rowland IR. Phyto-oestrogens, their mechanism of action: Current evidence for a role in breast and prostate cancer. British Journal of Nutrition 2004; 91: 513-531
19 Ososki AL, Kennelly EJ. Phytoestrogens: A Review of the Present State of Research. Phytotherapy Research 2003; 17: 845-869
20 Matsuda H, Shimoda H, Morikawa T. et al. Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): Structure-requirement of hydroxyl anthraquinones for estrogenic activity. Bioorg Mol Chem Lett 2001; 11: 1839-1842
21 Milligan SR, Kalita JC, Heyerick A. et al. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab 1999; 83: 2249-2252
22 Rafi MM, Rosen RT, Vassail A. et al. Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid. Anticancer Res 2000; 20: 2653-2658
23 Kim H, Peterson TG, Barnes S. Mechanisms of action of the soy isoflavone genistein: Emerging role for its effects via transforming growth factor b signaling pathways. Am J Clin Nutr 1998; 68 suppl 1418S-1425S
24 Chan KK, Siu MK, Jiang YX. et al. Estrogen receptor modulators genistein, daidzein and ERB-041 inhibit cell migration, invasion, proliferation and sphere formation via modulation of FAK and PI3K/AKT signaling in ovarian cancer. Cancer cell international 2018; 18: 65
25 Keating E, Martel F. Antimetabolic effects of polyphenols in breast cancer cells: Focus on glucose uptake and metabolism. Frontiers in nutrition 2018; 5: 25
26 Food Standards Agency 2003; Phytoestrogens and Health, Committee on Toxicology of Chemicals in Food, Consumer Products and the Environment https://cot.food.gov.uk/sites/default/files/cot/phytoreport0503.pdf
27 Kurzer MS. Phytoestrogen supplement use by women. The Journal of Nutrition 2003; 133: 1983S-1986S
28 Fotsis T, Pepper M, Adlercreutz H. et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proceedings National Academic Science USA 1993; 90: 2690-2694
29 Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effect of soy. Journal of Nutrition 1995; 125: 606S-611S
30 Setchell KDR, Lydeking OE. Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. American Journal of Clinical Nutrition 2003; 7: 593S-609S
31 Sakai T, Kogiso M. Soy isoflavones and immunity. The Journal of Medical Investigation 2008; 55: 167-173
32 Setchell KD, Faughnan MS, Avades T. et al. Comparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal women. Am J Clin Nutr 2003; 77: 411-419
33 Setchell KD, Brown NM, Desai P. et al. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr 2001; 131: 1362S-1375S
34 Chandrasekharan S, Aglin A. Pharmacokinetics of dietary isoflavones. J Steroids Hormon Sci 2013; S12: 2-8
35 Yang Z, Kulkarni K, Zhu W. et al. Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on its ADME. Anticancer Agents Med Chem 2012; 12: 1264-1280
36 Zaheer K, Akhtar MH. An Updated Review of Dietary Isoflavones: Nutrition, Processing, Bioavailability and Impacts on Human Health. Critical Reviews in Food Science and Nutrition 2017; 57: 1280-1293
37 de Oliveira MR. Evidence for genistein as a mitochondriotropic molecule. Mitochondrion 2016; 29: 35-44
38 Mazumder Md. AR, Hongsprabhas P. Genistein as antioxidant and antibrowning agents in in vivo and in vitro: A review. Biomed Pharmacother 2016; 82: 379-392
39 Yang Z, Zhu W, Gao S. et al. Simultaneous determination of genistein and its four phase II metabolites in blood by a sensitive and robust UPLC-MS/MS method: Application to an oral bioavailability study of genistein in mice. J Pharm Biomed Anal 2010; 53: 81-89
40 Shelnutt SR, Cimino CO, Wiggins PA. et al. Pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein in men and women after consumption of a soy beverage. Am J Clin Nutr 2002; 76: 588-594
41 Doerge DR, Chang HC, Churchwell MI. et al. Analysis of soy isoflavone conjugation in vitro and in human blood using liquid chromatography-mass spectrometry. Drug Metab Dispos 2000; 28: 298-307
42 Heinonen SM, Wähälä K, Adlercreutz H. Metabolism of isoflavones in human subjects. Phytochemistry Reviews 2002; 1: 175-182
43 Zhang Y, Hendrich S, Murphy PA. Glucuronides are the main isoflavone metabolites in women. J Nutr 2003; 133: 399-404
44 Steensma A, Faassen-Peters MA, Noteborn HP. et al. Bioavailability of genistein and its glycoside genistin as measured in the portalvein of freely moving unanesthetized rats. J Agric Food Chem 2006; 54: 8006-8012
45 Kwon SH, Kang MJ, Huh JS. et al. Comparison of oral bioavailability of genistein and genistin in rats. Int J Pharm 2007; 337: 148-154
46 Motlekar N, Khan MA, Youan BBC. Preparation and characterization of genistein containing poly (ethylene glycol) microparticles. J Appl Polym Sci 2006; 101: 2070-2078
47 Huang AS, Hsieh OAL, Chang SS. Characterization of the non-volatile minor constituents responsible for the objectionable taste of defatted soybean flour. J Food Sci 1982; 47: 19-23
48 Tamura M, Ohnishi-Kameyama M, Nakagawa H. et al Dihydrogenistein-producing bacterium TM-40 isolated from human feces. Food Sci Technol Res 2007; 13: 129-132
49 Sirtori CR. Risks and benefits of soy phytoestrogens in cardiovascular diseases, cancer, climacteric symptoms and osteoporosis. Drug Saf 2001; 24: 665-682
50 Bloedon LT, Jeffcoat AR, Lopaczynski W. et al Safety and pharmacokinetics of purified soy isoflavones: single dose administration to postmenopausal women. Am J Clin Nutr 2002; 76: 1126-1137
51 Klein CB, King AA. Genistein genotoxicity: Critical considerations of in vitro exposure dose. Toxicol Appl Pharmacol 2007; 224: 1-2211
52 Michael McClain R, Wolz E, Davidovich A. et al. Genetic toxicity studies with genistein. Food ChemToxicol 2006; 44: 42-55
53 Bloedon LT, Jeffcoat AR, Lopaczynski W. et al. Safety and pharmacokinetics of purified soy isoflavones: Single dose administration to postmenopausal women. Am J Clin Nutr 2002; 76: 1126-1137
54 Jefferson WN, Williams CJ. Circulating levels of genistein in the neonate, apart from dose and route, predict future adverse female reproductive outcomes. Reprod Toxicol 2011; 31: 272-279
55 Spagnuolo C, Russo GL, Orhan IE. et al. Genistein and cancer: Current status, challenges, and future directions. Advances in nutrition 2015; 6: 408-419
56 da Costa César I, Braga FC, Vianna-Soares CD. et al. Quantitation of genistein and genistin in soy dry extracts by UV-Visible spectrophotometric method. Quim. Nova 2008; 31: 1933-1936
57 Chang Hebron C, Churchwell MI, Delclos KB. et al. mass spectrometric determination of genistein tissue distribution in diet-exposed sprague-dawley rats. J Nutr 2000; 130: 1963-1970
58 Feng D, Qiu F, Tong Z. et al. oral pharmacokinetic comparison of different genistein tablets in beagle dogs. Journal of Chromatographic Science 2013; 51: 335-340
59 Holder CL, Churchwell MI, Doerge DR. quantification of soy isoflavones, genistein and daidzein, and conjugates in rat blood using LC/ES-MS. J. Agric. Food Chem 199 47: 3764-3770
60 Yang Z, Zhu W, Gao S. et al. Simultaneous determination of genistein and its four phase II metabolites in blood by a sensitive and robust UPLC-MS/MS method: Application to an oral bioavailability study of genistein in mice. J Pharm Biomed Anal 2010; 53: 81-89
61 Thomas BF, Zeisel SH, Busby MG. et al. Quantitative analysis of the principle soy isoflavones genistein, daidzein and glycitein, and their primary conjugated metabolites in human plasma and urine using reversed-phase high performance liquid chromatography with ultraviolet detection. Journal of Chromatography B 2001; 760: 191-205
62 Luo Y, Chen DW, Ren LX. et al. Solid lipid nanoparticles for enhancing vinpocetine’s oral bioavailability. J. Control. Release 2006; 114: 53-59
63 Muller RH, Runge S, Ravell V. et al. Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN) versus drug nanocrystals. Int J Pharm 2006; 317: 82-89
64 Wissing SA, Kayserb O, Muller RH. Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev 2004; 56: 1257-1272
65 Desai J, Thakkar H. Effect of particle size on oral bioavailability of darunavir-loaded solid lipid nanoparticles. J Microencapsul 2016; 33: 669-678
66 Horter D, Dressman JB. Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev 2001; 46: 75-87
67 Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - A review of the state of the art. Eur J Pharm Biopharm 2000; 50: 161-177
68 Kim JT, Barua S, Kim H. et al. Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes. Biomol Ther 2017; 25: 452-459
69 de Oliveira SR, Taveira SF, Marreto RN. et al. Preparation and characterization of solid oral dosage forms containing soy isoflavones. Brazilian Journal of Pharmacognosy 2013; 23: 175-181
70 Si H-Y, Li D-P, Wang T-M. et al. Improving the Anti-Tumor Effect of Genistein with a Biocompatible Superparamagnetic Drug Delivery System. Journal of Nanoscience and Nanotechnology 2010; 10: 1-7
71 Chen F, Peng J, Lei D. et al. Optimization of genistein solubilization by κ-carrageenan hydrogel using response surface methodology. Food Science and Human Wellness 2013; 2: 124-131
72 Kwon SH, Kim SY, Ha KW. et al. Pharmaceutical Evaluation of Genistein-loaded Pluronic Micelles for Oral Delivery. Arch Pharm Res 2007; 30: 1138-1143
73 Sahu AN. Nanotechnology in Herbal Medicines & Cosmetics. Int J Res Ayurveda Pharm 2013; 4: 472-474
74 NNI. 2005;National nanotechnology initiative: research and development leading to a revolution in technology and industry, office of sciences and technology policy, Washington, DC, USA http://www.nano.gov/nanotech-101/what
75 Ahmad J, Akhter S, Rizwanullah M. et al. Nanotechnology based inhalation treatments for lung cancer: state of the art. Nanotechnology Sci Appl 2015; 8: 55-66
76 Bhadoriya SS, Mangal A, Madoriya N. et al. Bioavailability and bioactivity enhancement of herbal drugs by nanotechnology: A review. J Curr Pharm Res 2011; 8: 1-7
77 Patel NR, Pattni BS, Abouzeid AH. et al. Nanopreparations to overcome multidrug resistance in cancer. Adv Drug Deliv Rev 2013; 65: 1748-1762
78 Peetla C, Vijayaraghavalu S, Labhasetwar V. Biophysics of cell membrane lipids in cancer drug resistance: implications for drug transport and drug delivery with nanoparticles. Adv Drug Deliv Rev 2013; 65: 1686-1698
79 Rizwanullah M, Amin S, Mir SR. et al. Phytochemical based nanomedicines against cancer: Current status and future prospects. J Drug Target 2017; 18: 1-22
80 Tosi G, Costantino L, Rivasi F. et al. Targeting the central nervous system: In vivo experiments with peptide-derivatized nanoparticles loaded with Loperamide and Rhodamine-123. J Control Release 2007; 122: 1-9
81 Mohanraj VJ, Chen Y. Nanoparticles – A Review. Tropical Journal of Pharmaceutical Research 2006; 5: 561-573
82 Barratt G. Colloidal drug carriers: Achievements and perspectives. Cell Mol Life Sci 2003; 60: 21-37
83 Tang J, Xu N, Ji H. et al. Eudragit nanoparticles containing genistein: Formulation, development, and bioavailability assessment. International Journal of Nanomedicine 2011; 6: 2429-2435
84 Zhang H, Liu G, Zeng X. et al. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells. International Journal of Nanomedicine 2015; 10: 2461-2473