Abstract
Genistein is considered one of the most active natural flavonoids. It has an isoflavonoid structure and expresses a variety of health benefits. This compound is considered one of the first choices for the prevention and treatment of many chronic diseases and several types of cancer as well. Since it is classified in the group of phytoestrogens, the area and complexity of its action are highly multidirectional. The main sources of genistein for human use are soy and soy-derived functional foods, but also some other plant species like dyer’s broom and red clover. It is biosynthesized via the shikimate pathway in plants and can be present in the form of its glucoside genistin. Genistein is quite simply metabolized after ingestion, but low absorption and biotransformation processes direct its bioavailability and further activity. Numerous in vitro, in vivo, and clinical studies were conducted to evaluate a broad range of genistein effects. It showed significant antioxidant, anti-inflammatory, anticancer, and antidiabetic properties, which, in combination with its estrogenic potential, may lead to the most profound effects on human health. Considering all aspects of genistein biosynthesis, bioavailability, metabolism, and biological activity, this chapter aimed to provide insight into most of the details related to its characteristics, resources, and usage in the general population.
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References
Ae Park S, Choi M-S, Cho S-Y et al (2006) Genistein and daidzein modulate hepatic glucose and lipid regulating enzyme activities in C57BL/KsJ-db/db mice. Life Sci 79:1207–1213. https://doi.org/10.1016/j.lfs.2006.03.022
Agarwal R (2000) Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents. Biochem Pharmacol 60:1051–1059. https://doi.org/10.1016/S0006-2952(00)00385-3
Ajdžanović VZ, Šošič-Jurjević BT, Filipović B et al (2009) Genistein affects the morphology of pituitary ACTH cells and decreases circulating levels of ACTH and corticosterone in middle-aged male rats. Biol Res 42:13–23. https://doi.org/10.4067/s0716-97602009000100002
Amanat S, Eftekhari MH, Fararouei M et al (2018) Genistein supplementation improves insulin resistance and inflammatory state in non-alcoholic fatty liver patients: a randomized, controlled trial. Clin Nutr 37:1210–1215. https://doi.org/10.1016/j.clnu.2017.05.028
Babu PVA, Si H, Fu Z et al (2012) Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic endothelial cells through preservation of the camp signaling pathway and ameliorates vascular inflammation in obese diabetic mice. J Nutr 142:724–730. https://doi.org/10.3945/jn.111.152322
Barnes S, Peterson TG (1995) Biochemical targets of the isoflavone genistein in tumor cell lines. Proc Soc Exp Biol Med 208:103–108. https://doi.org/10.3181/00379727-208-43840
Behloul N, Wu G (2013) Genistein: a promising therapeutic agent for obesity and diabetes treatment. Eur J Pharmacol 698:31–38. https://doi.org/10.1016/j.ejphar.2012.11.013
Berkenstam A, Rehnmark S, Witt M-R, Watt S (2011) Crystalline genistein sodium salt dihydrate, United States Patent No. US 7,863,325 B2; Axcentua Pharmaceuticals AB (SE), 2011-01-04.
Bhat SS, Prasad SK, Shivamallu C et al (2021) Genistein: a potent anti-breast cancer agent. Curr Issues Mol Biol 43:1502–1517. https://doi.org/10.3390/cimb43030106
Bowey E, Adlercreutz H, Rowland I (2003) Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats. Food Chem Toxicol 41:631–636. https://doi.org/10.1016/S0278-6915(02)00324-1
Braxas H, Rafraf M, Karimi Hasanabad S, Asghari Jafarabadi M (2019) Effectiveness of genistein supplementation on metabolic factors and antioxidant status in postmenopausal women with type 2 diabetes mellitus. Can J Diabetes 43:490–497. https://doi.org/10.1016/j.jcjd.2019.04.007
Cai Q, Wei H (1996) Effect of dietary genistein on antioxidant enzyme activities in SENCAR mice. Nutr Cancer 25:1–7. https://doi.org/10.1080/01635589609514423
Ceccarelli I, Bioletti L, Peparini S et al (2022) Estrogens and phytoestrogens in body functions. Neurosci Biobehav Rev 132:648–663. https://doi.org/10.1016/j.neubiorev.2021.12.007
Cederroth CR, Zimmermann C, Nef S (2012) Soy, phytoestrogens and their impact on reproductive health. Mol Cell Endocrinol 355:192–200. https://doi.org/10.1016/j.mce.2011.05.049
Cepeda SB, Sandoval MJ, Rauschemberger MB, Massheimer VL (2017) Beneficial role of the phytoestrogen genistein on vascular calcification. J Nutr Biochem 50:26–37. https://doi.org/10.1016/j.jnutbio.2017.08.009
Chang TS, Ding HY, Tai SSK, Wu CY (2007) Metabolism of the soy isoflavones daidzein and genistein by fungi used in the preparation of various fermented soybean foods. Biosci Biotechnol Biochem 71:1330–1333. https://doi.org/10.1271/bbb.60573
Chantalat E, Valera M-C, Vaysse C et al (2020) Estrogen receptors and endometriosis. Int J Mol Sci 21:2815. https://doi.org/10.3390/ijms21082815
Chen Y, Jefferson WN, Newbold RR et al (2007) Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo. Endocrinology 148:3580–3590. https://doi.org/10.1210/EN.2007-0088
Chiang CM, Ding HY, Lu JY, Chang TS (2016) Biotransformation of isoflavones daidzein and genistein by recombinant Pichia pastoris expressing membrane-anchoring and reductase fusion chimeric CYP105D7. J Taiwan Inst Chem Eng 60:26–31. https://doi.org/10.1016/j.jtice.2015.10.015
Cho SH, Jo A, Casale T et al (2019) Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1–producing genotypes. J Allergy Clin Immunol 144:109–117.e4. https://doi.org/10.1016/j.jaci.2019.01.020
Choi HR, Park JS, Kim KM et al (2018) Enhancing the antimicrobial effect of genistein by biotransformation in microbial system. J Ind Eng Chem 63:255–261. https://doi.org/10.1016/j.jiec.2018.02.023
Chow YY, Chin KY (2020) The role of inflammation in the pathogenesis of osteoarthritis. Mediat Inflamm 2020:1. https://doi.org/10.1155/2020/8293921
Cos P, De Bruyne T, Apers S et al (2003) Phytoestrogens: recent developments. Planta Med 69:589–599. https://doi.org/10.1055/s-2003-41122
Cotroneo MS, Lamartiniere CA (2001) Pharmacologic, but not dietary, genistein supports endometriosis in a rat model. Toxicol Sci 61:68
Davis JN, Kucuk O, Sarkar FH (1999) Genistein inhibits NF-kB activation in prostate cancer cells. Nutr Cancer 35:167–174
Davis JN, Kucuk O, Djuric Z, Sarkar FH (2001) Soy isoflavone supplementation in healthy men prevents NF-kB activation by TNF-alpha in blood lymphocytes. Free Radic Biol Med 30:1293–1302
Dewick PM (2009) Medicinal natural products a biosynthetic approach, 3rd edn. Wiley, Chichester
Di Lorenzo C, Colombo F, Biella S et al (2021) Polyphenols and human health: the role of bioavailability. Nutrients 13:1–30
Diel P, Olff S, Schmidt S, Michna H (2001) Molecular identification of potential selective estrogen receptor modulator (SERM) like properties of phytoestrogens in the human breast cancer cell line MCF-7. Planta Med 67:510–514. https://doi.org/10.1055/s-2001-16474
Dixon RA, Ferreira D (2002) Genistein. Phytochemistry 60:205–211
Dong JY, Kimura T, Ikehara S et al (2021) Soy consumption and incidence of gestational diabetes mellitus: the Japan Environment and Children’s Study. Eur J Nutr 60:897–904. https://doi.org/10.1007/s00394-020-02294-1
Elmarakby AA, Ibrahim AS, Faulkner J et al (2011) Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin-induced diabetic mice. Vasc Pharmacol 55:149–156. https://doi.org/10.1016/j.vph.2011.07.007
Evans WC (2002) Trease & Evans pharmacognosy, 15th edn. Elsevier (A Division of Reed Elsevier India Pvt. Limited), Delhi
Fang Y, Zhang Q, Wang X et al (2016) Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells. Int J Oncol 48:1016–1028. https://doi.org/10.3892/ijo.2016.3327
Fraga CG, Oteiza PI (2011) Dietary flavonoids: role of(−)-epicatechin and related procyanidins in cell signaling. Free Radic Biol Med 51:813–823. https://doi.org/10.1016/j.freeradbiomed.2011.06.002
Fu Z, Zhang W, Zhen W et al (2010) Genistein induces pancreatic β-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice. Endocrinology 151:3026–3037. https://doi.org/10.1210/en.2009-1294
Fuloria S, Yusri MAA, Sekar M et al (2022) Genistein: a potential natural lead molecule for new drug design and development for treating memory impairment. Molecules 27:265. https://doi.org/10.3390/molecules27010265
Ganai AA, Farooqi H (2015) Bioactivity of genistein: a review of in vitro and in vivo studies. Biomed Pharmacother 76:30–38. https://doi.org/10.1016/J.BIOPHA.2015.10.026
Gao QG, Xie JX, Wong MS, Chen WF (2012) IGF-I receptor signaling pathway is involved in the neuroprotective effect of genistein in the neuroblastoma SK-N-SH cells. Eur J Pharmacol 677:39–46. https://doi.org/10.1016/j.ejphar.2011.12.032
Garbiec E, Cielecka-Piontek J, Kowalówka M et al (2022) Genistein – opportunities related to an interesting molecule of natural origin. Molecules 27:815. https://doi.org/10.3390/molecules27030815
George J, Banik NL, Ray SK (2010) Genistein induces receptor and mitochondrial pathways and increases apoptosis during Bcl-2 knockdown in human malignant neuroblastoma SK-N-DZ cells. J Neurosci Res 88:877–886. https://doi.org/10.1002/jnr.22244
Gilbert ER, Liu D (2013) Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function. Food Funct 4:200–212. https://doi.org/10.1039/c2fo30199g
Goh YX, Jalil J, Lam KW et al (2022) Genistein: a review on its anti-inflammatory properties. Front Pharmacol 13:820969. https://doi.org/10.3389/fphar.2022.820969
Guo TL, Chen Y, Xu HS et al (2020) Gut microbiome in neuroendocrine and neuroimmune interactions: the case of genistein. Toxicol Appl Pharmacol 402:115130. https://doi.org/10.1016/j.taap.2020.115130
Hamza Sherif S, Gebreyohannes BT (2018) Synthesis, characterization, and antioxidant activities of genistein, biochanin A, and their analogues. J Chem 2018:2–8. https://doi.org/10.1155/2018/4032105
Heinonen SM, Hoikkala A, Wähälä K, Adlercreutz H (2003) Metabolism of the soy isoflavones daidzein, genistein and glycitein in human subjects. Identification of new metabolites having an intact isoflavonoid skeleton. J Steroid Biochem Mol Biol 87:285–299. https://doi.org/10.1016/j.jsbmb.2003.09.003
Hu S-C, Hong K, Song Y-C et al (2009) Biotransformation of soybean isoflavones by a marine Streptomyces sp. 060524 and cytotoxicity of the products. World J Microbiol Biotechnol 25:115–121. https://doi.org/10.1007/s11274-008-9872-6
Ionescu VS, Popa A, Alexandru A et al (2021) Dietary phytoestrogens and their metabolites as epigenetic modulators with impact on human health. Antioxidants 10:1893. https://doi.org/10.3390/antiox10121893
Ivanović N, Jovanović L, Marković Z et al (2016) Potent 1,2,4-triazole-3-thione radical scavengers derived from phenolic acids: synthesis, electrochemistry, and theoretical study. ChemistrySelect 1:3870–3878. https://doi.org/10.1002/slct.201600738
Jamilian M, Asemi Z (2016) The effects of soy isoflavones on metabolic status of patients with polycystic ovary syndrome. J Clin Endocrinol Metab 101:3386–3394. https://doi.org/10.1210/JC.2016-1762
Javanbakht MH, Sadria R, Djalali M et al (2014) Soy protein and genistein improves renal antioxidant status in experimental nephrotic syndrome. Nefrologia 34:483–490. https://doi.org/10.3265/Nefrologia.pre2014.Jun.12051
Jung YS, Rha C-S, Baik M-Y et al (2020) A brief history and spectroscopic analysis of soy isoflavones. Food Sci Biotechnol 29:1605–1617. https://doi.org/10.1007/s10068-020-00815-6
Katanić Stanković JS, Srećković N, Mišić D et al (2020) Bioactivity, biocompatibility and phytochemical assessment of lilac sage, Salvia verticillata L. (Lamiaceae) – a plant rich in rosmarinic acid. Ind Crops Prod 143:111932. https://doi.org/10.1016/j.indcrop.2019.111932
Katanić J, Boroja T, Stanković N et al (2015a) Bioactivity, stability and phenolic characterization of Filipendula ulmaria (L.) Maxim. Food Funct 6:1164–1175. https://doi.org/10.1039/C4FO01208A
Katanić J, Mihailović V, Stanković N et al (2015b) Dropwort (Filipendula hexapetala Gilib.): potential role as antioxidant and antimicrobial agent. EXCLI J 14:1–20. https://doi.org/10.17179/excli2014-479
Katanić J, Boroja T, Mihailović V et al (2016) In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent. J Ethnopharmacol 193:627–636. https://doi.org/10.1016/j.jep.2016.10.015
Khani B, Mehrabian F, Khalesi E, Eshraghid A (2011) Effect of soy phytoestrogen on metabolic and hormonal disturbance of women with polycystic ovary syndrome. J Res Med Sci 16:297
Kładna A, Berczyński P, Kruk I et al (2016) Studies on the antioxidant properties of some phytoestrogens. Luminescence 31:1201–1206. https://doi.org/10.1002/bio.3091
Lakshman M, Xu L, Ananthanarayanan V et al (2008) Dietary genistein inhibits metastasis of human prostate cancer in mice. Cancer Res 68:2024–2032. https://doi.org/10.1158/0008-5472.CAN-07-1246
Lecomte S, Demay F, Ferrière F, Pakdel F (2017) Phytochemicals targeting estrogen receptors: beneficial rather than adverse effects? Int J Mol Sci 18:1381. https://doi.org/10.3390/ijms18071381
Lee JS (2006) Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats. Life Sci 79:1578–1584. https://doi.org/10.1016/j.lfs.2006.06.030
Lee CH, Yang L, Xu JZ et al (2005) Relative antioxidant activity of soybean isoflavones and their glycosides. Food Chem 90:735–741. https://doi.org/10.1016/j.foodchem.2004.04.034
Lewicki S, Lewicka A, Kalicki B et al (2018) Effects of genistein on insulin pathway-related genes in mouse differentiated myoblast C2C12 cell line: evidence for two independent modes of action. Folia Histochem Cytobiol 56:123–132. https://doi.org/10.5603/FHC.a2018.0014
Li H, Xu W, Huang Y et al (2012) Genistein demethylates the promoter of CHD5 and inhibits neuroblastoma growth in vivo. Int J Mol Med 30:1081–1086. https://doi.org/10.3892/ijmm.2012.1118
Liu Y, Zou T, Wang S et al (2016) Genistein-induced differentiation of breast cancer stem/progenitor cells through a paracrine mechanism. Int J Oncol 48:1063–1072. https://doi.org/10.3892/ijo.2016.3351
Lopes De Azambuja CR, Dos Santos LG, Rodrigues MR et al (2015) Physico-chemical characterization of asolectin-genistein liposomal system: an approach to analyze its in vitro antioxidant potential and effect in glioma cells viability. Chem Phys Lipids 193:24–35. https://doi.org/10.1016/j.chemphyslip.2015.10.001
Lu C, Lv J, Jiang N et al (2020) Protective effects of Genistein on the cognitive deficits induced by chronic sleep deprivation. Phyther Res 34:846–858. https://doi.org/10.1002/ptr.6567
Malloy KM, Wang J, Clark LH et al (2018) Novasoy and genistein inhibit endometrial cancer cell proliferation through disruption of the AKT/mTOR and MAPK signaling pathways. Am J Transl Res 10:784–795
McClain RM, Wolz E, Davidovich A et al (2005) Subchronic and chronic safety studies with genistein in dogs. Food Chem Toxicol 43:1461–1482. https://doi.org/10.1016/j.fct.2005.02.017
McClain RM, Wolz E, Davidovich A et al (2006) Acute, subchronic and chronic safety studies with genistein in rats. Food Chem Toxicol 44:56–80. https://doi.org/10.1016/j.fct.2005.05.021
McClain RM, Wolz E, Davidovich A et al (2007) Reproductive safety studies with genistein in rats. Food Chem Toxicol 45:1319–1332. https://doi.org/10.1016/j.fct.2007.01.009
Mei J, Chen X, Liu J et al (2019) A biotransformation process for production of genistein from sophoricoside by a strain of Rhizopus oryza. Sci Rep 9:2–6. https://doi.org/10.1038/s41598-019-42996-z
Mihailović V, Kreft S, Benković ET et al (2016) Chemical profile, antioxidant activity and stability in stimulated gastrointestinal tract model system of three Verbascum species. Ind Crop Prod 89:141–151. https://doi.org/10.1016/j.indcrop.2016.04.075
Mihailović N, Marković V, Matić IZ et al (2017) Synthesis and antioxidant activity of 1,3,4-oxadiazoles and their diacylhydrazine precursors derived from phenolic acids. RSC Adv 7:8550–8560. https://doi.org/10.1039/c6ra28787e
Mihailović NR, Mihailović VB, Kreft S et al (2018) Analysis of phenolics in the peel and pulp of wild apples (Malus sylvestris (L.) Mill.). J Food Compos Anal 67:1–9. https://doi.org/10.1016/j.jfca.2017.11.007
Mihailović V, Katanić Stanković JS, Mihailović N (2020) Phenolic compounds diversity of Teucrium species. In: Stanković MS (ed) Teucrium species: biology and applications. Springer Nature Switzerland AG, Cham, pp 143–178
Miljkovic D, Geller J, Olbina G (1998) The use of genistein and related compounds to treat certain sex hormone related conditions. pp 1–22. Publication Number WO/1998/048790
Mirahmadi SMS, Shahmohammadi A, Rousta AM et al (2017) Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects. Cytokine 104:151. https://doi.org/10.1016/j.cyto.2017.10.008
Mititelu RR, Pădureanu R, Băcănoiu M et al (2020) Inflammatory and oxidative stress markers-mirror tools in rheumatoid arthritis. Biomedicine 8:1–14. https://doi.org/10.3390/BIOMEDICINES8050125
Mohan N, Chakrabarti M, Banik NL, Ray SK (2013) Combination of LC3 shRNA plasmid transfection and genistein treatment inhibited autophagy and increased apoptosis in malignant neuroblastoma in cell culture and animal models. PLoS One 8:1–16. https://doi.org/10.1371/journal.pone.0078958
Mukund V, Mukund D, Sharma V et al (2017) Genistein: its role in metabolic diseases and cancer. Crit Rev Oncol Hematol 119:13–22. https://doi.org/10.1016/j.critrevonc.2017.09.004
Nathan C, Ding A (2010) Nonresolving inflammation. Cell 140:871–882. https://doi.org/10.1016/j.cell.2010.02.029
Nayeem F, Chen NW, Nagamani M et al (2019) Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: a 2-year randomized, double-blind, placebo-controlled study. Nutr Res 68:70–81. https://doi.org/10.1016/j.nutres.2019.06.007
Nazari-Khanamiri F, Ghasemnejad-Berenji M (2021) Cellular and molecular mechanisms of genistein in prevention and treatment of diseases: an overview. J Food Biochem 45:127–137. https://doi.org/10.1111/jfbc.13972
Nielsen ILF, Williamson G (2007) Review of the factors affecting bioavailability of soy isoflavones in humans. Nutr Cancer 57:1–10. https://doi.org/10.1080/01635580701267677
Obata A, Matsuura M (1993) Production of genistein, Japan, Patent No. JPH07173148A, Kikkoman Corp, 1993-12-17.
Paterni I, Granchi C, Katzenellenbogen JA, Minutolo F (2014) Estrogen receptors alpha (ERα) and beta (ERβ): subtype-selective ligands and clinical potential. Steroids 90:13–29. https://doi.org/10.1016/j.steroids.2014.06.012
Paulo A, Mota-Filipe H (2006) Effects of some natural 5-hydroxy-isoflavones on cultured human endothelial cells in presence and absence of hydrogen peroxide. J Pharm Pharmacol 58:101–105. https://doi.org/10.1211/jpp.58.1.0012
Pierzynowska K, Cyske Z, Gaffke L et al (2021) Potencjał autofagii indukowanej przez genisteinę w leczeniu chorób neurodegeneracyjnych. Postepy Biochem 67:117–129. https://doi.org/10.18388/pb.2021_380
Pihlajamaa P, Zhang FP, Saarinen L et al (2011) The phytoestrogen genistein is a tissue-specific androgen receptor modulator. Endocrinology 152:4395–4405. https://doi.org/10.1210/EN.2011-0221
Pintova S, Dharmupari S, Moshier E et al (2019) Genistein combined with FOLFOX or FOLFOX–Bevacizumab for the treatment of metastatic colorectal cancer: phase I/II pilot study. Cancer Chemother Pharmacol 84:591–598. https://doi.org/10.1007/s00280-019-03886-3
Popović-Djordjević JB, Katanić Stanković JS, Mihailović V, Muhammad A (2021) Biochemistry and metabolism. In: Galanakis CM (ed) Saffron. Elsevier Academic Press, London, United Kingdom, pp 1–39
Rahman Mazumder MA, Hongsprabhas P (2016) Genistein as antioxidant and antibrowning agents in in vivo and in vitro: a review. Biomed Pharmacother 82:379–392. https://doi.org/10.1016/j.biopha.2016.05.023
Record IR, Dreosti IE, McInerney JK (1995) The antioxidant activity of genistein in vitro. J Nutr Biochem 6:481–485. https://doi.org/10.1016/0955-2863(95)00076-C
Rowland I, Faughnan M, Hoey L et al (2003) Bioavailability of phyto-oestrogens. Br J Nutr 89:S45–S58. https://doi.org/10.1079/BJN2002796
Saltveit ME (2017) Synthesis and metabolism of phenolic compounds. In: Fruit and vegetable phytochemicals. Wiley, Chichester, pp 115–124
Samuelsson G, Bohlin L (2015) Drugs of natural origin – a treatise of pharmacognosy, 7th edn. Swedish Pharmaceutical Society, Stockholm
Schneider LS, Hernandez G, Zhao L et al (2019) Safety and feasibility of estrogen receptor-β targeted phytoSERM formulation for menopausal symptoms: phase 1b/2a randomized clinical trial. Menopause 26:874–884. https://doi.org/10.1097/GME.0000000000001325
Schoefer L, Mohan R, Braune A et al (2002) Anaerobic C-ring cleavage of genistein and daidzein by Eubacterium ramulus. FEMS Microbiol Lett 208:197–202. https://doi.org/10.1016/S0378-1097(02)00458-5
Sekar V, Anandasadagopan SK, Ganapasam S (2016) Genistein regulates tumor microenvironment and exhibits anticancer effect in dimethyl hydrazine-induced experimental colon carcinogenesis. Biofactors 42:623–637. https://doi.org/10.1002/biof.1298
Selma MV, Espín JC, Tomás-Barberán FA (2009) Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 57:6485–6501
Sha GH, Lin SQ (2008) Genistein inhibits proliferation of human endometrial endothelial cell in vitro. Chin Med Sci J 23:49–53. https://doi.org/10.1016/S1001-9294(09)60010-9
Shao J, Zhao T, Ma HP et al (2020) Synthesis, characterization, and antioxidant activity of 8-hydroxygenistein. Nat Prod Commun 15:1–7. https://doi.org/10.1177/1934578X20901399
Shrestha L, Marasini BP, Pradhan SP et al (2021) Biotransformation of daidzein, genistein, and naringenin by streptomyces species isolated from high-altitude soil of Nepal. Int J Microbiol 2021:1–8. https://doi.org/10.1155/2021/9948738
Singh P, Sharma S, Kumar Rath S (2014) Genistein induces deleterious effects during its acute exposure in Swiss mice. Biomed Res Int 2014:1. https://doi.org/10.1155/2014/619617
Siti HN, Kamisah Y, Kamsiah J (2015) The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vasc Pharmacol 71:40–56. https://doi.org/10.1016/j.vph.2015.03.005
Srećković N, Katanić Stanković JS, Matić S et al (2020) Lythrum salicaria L. (Lythraceae) as a promising source of phenolic compounds in the modulation of oxidative stress: comparison between aerial parts and root extracts. Ind Crops Prod 155:112781. https://doi.org/10.1016/j.indcrop.2020.112781
Sureda A, Sanches Silva A, Sánchez-Machado DI et al (2017) Hypotensive effects of genistein: from chemistry to medicine. Chem Biol Interact 268:37–46. https://doi.org/10.1016/j.cbi.2017.02.012
Sutrisno S, Sulistyorini C, Manungkalit EM et al (2017) The effect of genistein on TGF-β signal, dysregulation of apoptosis, cyclooxygenase-2 pathway, and NF-kB pathway in mice peritoneum of endometriosis model. Middle East Fertil Soc J 22:295–299. https://doi.org/10.1016/j.mefs.2017.05.002
Sutrisno S, Aprina H, Simanungkalit HM et al (2018) Genistein modulates the estrogen receptor and suppresses angiogenesis and inflammation in the murine model of peritoneal endometriosis. J Tradit Complement Med 8:278–281. https://doi.org/10.1016/j.jtcme.2017.03.002
Swami S, Krishnan AV, Moreno J et al (2009) Inhibition of prostaglandin synthesis and actions by genistein in human prostate cancer cells and by soy isoflavones in prostate cancer patients. Int J Cancer 124:2050–2059. https://doi.org/10.1002/ijc.24161
Tabary O, Escotte S, Couetil JP et al (1999) Genistein inhibits constitutive and inducible NFκB activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells. Am J Pathol 155:473–481. https://doi.org/10.1016/S0002-9440(10)65143-7
Temerdashev ZA, Chubukina TK, Vinitskaya EA et al (2021) Assessment of the concentrations of isoflavonoids in red clover (Trifolium pratense L.) of the fabaceae family using extraction by different methods. J Anal Chem 76:819–831. https://doi.org/10.1134/S1061934821090112
Tsuchiya M, Miura T, Hanaoka T et al (2007) Effect of soy isoflavones on endometriosis: interaction with estrogen receptor 2 gene polymorphism. Epidemiology 18:402–408. https://doi.org/10.1097/01.EDE.0000257571.01358.F9
USDA (2007) USDA-Iowa State University Database on the isoflavone content of foods. Release 1.4 April 2007. Available at: https://www.ars.usda.gov/ARSUserFiles/80400525/data/isoflav/isoflav1-4.pdf. Accessed 08 July 2022
Velderrain-Rodríguez GR, Palafox-Carlos H, Wall-Medrano A et al (2014) Phenolic compounds: their journey after intake. Food Funct 5:189–197. https://doi.org/10.1039/c3fo60361j
Verdrengh M, Jonsson IM, Holmdahl R, Tarkowski A (2003) Genistein as an anti-inflammatory agent. Inflamm Res 52:341–346. https://doi.org/10.1007/s00011-003-1182-8
Vermerris W, Nicholson R (2006) Phenolic compounds biochemistry. Springer, Dordrecht
Walter E (1941) Genistin (an isoflavone glucoside) and its aglucone, genistein, from soybeans. J Am Chem Soc 63:3273–3276
Wang Q, Brubaker P (2002) Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia 45:1263–1273. https://doi.org/10.1007/s00125-002-0828-3
Wang XL, Kim KT, Lee JH et al (2004) C-ring cleavage of isoflavones daidzein and genistein by a newly-isolated human intestinal bacterium Eubacterium ramulus Julong 601. J Microbiol Biotechnol 14:766–771
Wang J, Shang F, Liu L et al (2007) In vivo and in vitro activity of genistein in osteoporosis. Indian J Pharmacol 39:103–106
Wang A, Wei J, Lu C et al (2019) Genistein suppresses psoriasis-related inflammation through a STAT3–NF-κB-dependent mechanism in keratinocytes. Int Immunopharmacol 69:270–278. https://doi.org/10.1016/j.intimp.2019.01.054
Weber MJ, Constantinou A, Hessler PE (1996) Process of preparing genistein, United States Patent No. US 5,554,51;FermaLogic, Inc., Chicago, Ill., 1996-09-10.
Wei H (1998) Genistein as a preventive against ultraviolet induced skin photodamage and cancer, United States Patent No. US 5,824,702;Mount Sinai School of Medicine of the City University of New York, New York, N.Y., 1998-10-20.
Wei H, Bowen R, Cai Q, et al (1995) Antioxidant and antipromotional effects of the soybean isoflavone genistein. Exp Biol Med http://ebm.sagepub.com/ Antioxid 208:124–130. https://doi.org/10.3181/00379727-208-43844
Widowati W, Prahastuti S, Ekayanti NLW et al (2019) Anti-inflammation assay of black soybean extract and its compounds on lipopolysaccharide-induced RAW 264.7 cell. J Phys Conf Ser 1374:1–11. https://doi.org/10.1088/1742-6596/1374/1/012052
Xu L, Liu J-T, Li K et al (2019) Genistein inhibits Ang II-induced CRP and MMP-9 generations via the ER-p38/ERK1/2-PPARγ-NF-κB signaling pathway in rat vascular smooth muscle cells. Life Sci 216:140–146. https://doi.org/10.1016/j.lfs.2018.11.036
Yang Y-Y, Tsai T-H (2019) Enterohepatic circulation and pharmacokinetics of genistin and genistein in rats. ACS Omega 4:18428–18433. https://doi.org/10.1021/acsomega.9b02762
Yang W, Wang S, Li L et al (2011) Genistein reduces hyperglycemia and islet cell loss in a high-dosage manner in rats with alloxan-induced pancreatic damage. Pancreas 40:396–402. https://doi.org/10.1097/MPA.0b013e318204e74d
Yang Z, Kulkarni K, Zhu W, Hu M (2012) Bioavailability and pharmacokinetics of genistein: mechanistic studies on its ADME. Anti Cancer Agents Med Chem 12:1264–1280. https://doi.org/10.2174/187152012803833107
Yang L, Zhang W, Zhi S et al (2022) Effects of genistein on glucose and lipid metabolism of common carp (Cyprinus carpio. L) in vivo and in vitro. Aquac Rep 22:100930. https://doi.org/10.1016/j.aqrep.2021.100930
Yao LH, Jiang YM, Shi J et al (2004) Flavonoids in food and their health benefits. Plant Foods Hum Nutr 59:113–122. https://doi.org/10.1007/s11130-004-0049-7
Yavuz E, Oktem M, Esinler I et al (2007) Genistein causes regression of endometriotic implants in the rat model. Fertil Steril 88:1129–1134. https://doi.org/10.1016/J.FERTNSTERT.2007.01.010
Ye L, Chan MY, Leung LK (2009) The soy isoflavone genistein induces estrogen synthesis in an extragonadal pathway. Mol Cell Endocrinol 302:73–80. https://doi.org/10.1016/j.mce.2009.01.003
Yu X, Zhu J, Mi M et al (2012) Anti-angiogenic genistein inhibits VEGF-induced endothelial cell activation by decreasing PTK activity and MAPK activation. Med Oncol 29:349–357. https://doi.org/10.1007/s12032-010-9770-2
Yu L, Rios E, Castro L et al (2021) Genistein: dual role in women’s health. Nutrients 13:3048. https://doi.org/10.3390/nu13093048
Yun J, Lee CK, Chang IM et al (2000) Differential inhibitory effects of sophoricoside analogs on bioactivity of several cytokines. Life Sci 67:2855–2863. https://doi.org/10.1016/S0024-3205(00)00873-0
Zhao X, Yuan L, Yu H et al (2014) Genistein inhibited amyloid-β induced inflammatory damage in C6 glial cells. Arch Med Res 45:152–157. https://doi.org/10.1016/j.arcmed.2013.12.008
Zhao QX, Zhao M, Parris AB et al (2016) Genistein targets the cancerous inhibitor of PP2A to induce growth inhibition and apoptosis in breast cancer cells. Int J Oncol 49:1203–1210. https://doi.org/10.3892/ijo.2016.3588
Zheng J, Li H, Zhu H et al (2013) Genistein inhibits estradiol- and environmental endocrine disruptor-induced growth effects on neuroblastoma cells in vitro. Oncol Lett 5:1583–1586. https://doi.org/10.3892/ol.2013.1236
Zhu Q, Zhang W, Mu D et al (2020) Effects of genistein on lipopolysaccharide-induced injury of mouse alveolar epithelial cells and its mechanism. Biosci Biotechnol Biochem 84:544–551. https://doi.org/10.1080/09168451.2019.1697197
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The Ministry of Science, Technological Development and Innovation of the Republic of Serbia supported the authors’ work (Agreements No. 451-03-47/2023-01/200378 and 451-03-47/2023-01/200122).
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Katanić Stanković, J.S., Mihailović, N., Mihailović, V. (2023). Genistein: Advances on Resources, Biosynthesis Pathway, Bioavailability, Bioactivity, and Pharmacology. In: Xiao, J. (eds) Handbook of Dietary Flavonoids. Springer, Cham. https://doi.org/10.1007/978-3-030-94753-8_45-1
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