Drug Res (Stuttg) 2024; 74(09): 433-455
DOI: 10.1055/a-2379-6849
Review

Bioflavonoid Daidzein: Therapeutic Insights, Formulation Advances, and Future Directions

Shafiurrahman 1
Sana Ahmad
1   Department of Pharmacy, Integral University, Dasauli, Kursi road, Lucknow (U.P.)-India
,
Farogh Ahsan
1   Department of Pharmacy, Integral University, Dasauli, Kursi road, Lucknow (U.P.)-India
,
Javed Akhtar Ansari
1   Department of Pharmacy, Integral University, Dasauli, Kursi road, Lucknow (U.P.)-India
,
Tarique Mahmood
1   Department of Pharmacy, Integral University, Dasauli, Kursi road, Lucknow (U.P.)-India
,
Shahzadi Bano
2   Department of Chemistry, Integral University, Dasauli, Kursi road, Lucknow (U.P.)-India
,
Mo. Shahanawaz
1   Department of Pharmacy, Integral University, Dasauli, Kursi road, Lucknow (U.P.)-India
› Author Affiliations
Funding Source This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Abstract

Bioflavonoids, are a diverse group of phytonutrients that are widely distributed in fruits, vegetables, grains, teas, and certain medicinal herbs. They are characterized by their antioxidant properties and play essential roles in plant biology, such as providing color to fruits and flowers, protecting plants from environmental stresses. Daidzein, a bioflavonoid classified under natural products, is sourced from plants like soybeans and legumes. It exists in forms such as glycosides and aglycones, with equol and trihydroxy isoflavone being key metabolites formed by gut bacteria. Known for its wide-ranging therapeutic potential, daidzein has shown effects on cardiovascular health, cancer, diabetes, skin conditions, osteoporosis, and neurodegenerative disorders. Its mechanisms include interaction with estrogen receptors, antioxidative and anti-inflammatory properties, and modulation of apoptosis and cell cycles. Recent advances in formulation technologies aimed at enhancing daidzeinʼs bioavailability and efficacy are critically evaluated, including nanoparticle-based delivery systems and encapsulation strategies. Researchers have developed advanced formulations like nanoparticles and liposomes to enhance daidzeinʼs solubility, stability, bioavailability, and targeted delivery. Considered a promising nutraceutical, daidzein warrants further exploration into its molecular actions and safety profile to fully realize its clinical potential. This review offers a succinct overview encompassing therapeutic benefits, chemical characteristics, historical uses, toxicology insights, recent advancements in delivery systems, and future directions for daidzein research.



Publication History

Received: 20 June 2024

Accepted: 29 July 2024

Article published online:
19 September 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Alam M, Ahsan F, Mahmood T. et al. Meticulous parade on naringin respecting its pharmacological activities and novel formulations. Avicenna J Phytomedicine 2022; 12: 474
  • 2 Křížová L, Dadáková K, Kašparovská J. et al. Isoflavones. Molecules 2019; 24: 1084
  • 3 Cook N, Samman S. Flavonoids—Chemistry, metabolism, cardioprotective effects, and dietary sources. J Nutr Biochem 1996; 7: 66-76
  • 4 Bhagwat S, Haytowitz D. USDA database for the flavonoid content of selected foods. 2022
  • 5 Tiwari P, Ansari VA, Mahmood T. et al. A review on taxonomical classification, phytochemical constituents and therapeutic potential of Ficus religiosa (Peepal). Res J Pharm Technol 2019; 12: 5614-5620
  • 6 Narayana K, Reddy M, Chaluvadi M. et al. Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential. Indian J Pharmacol 2001; 33: 2-16
  • 7 Sun MY, Ye Y, Xiao L. et al. Daidzein: A review of pharmacological effects. African J Tradit Complement Altern Med 2016; 13: 117-132
  • 8 De Lemos ML. Effects of soy phytoestrogens genistein and daidzein on breast cancer growth. Ann Pharmacother 2001; 35: 1118-1121
  • 9 Khaodhiar L, Ricciotti HA, Li L. et al. Daidzein-rich isoflavone aglycones are potentially effective in reducing hot flashes in menopausal women. Menopause 2008; 15: 132
  • 10 Association of Serum Phytoestrogen Concentration and Dietary Habits in a Sample Set of the JACC Study. J Epidemiol 2005; 15: S202
  • 11 Barnes S, Peterson TG, Coward L. Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cell Biochem Suppl 1995; 22: 181-187
  • 12 Keservani RK, Kesharwani RK, Vyas N. et al. Nutraceutical and Functional Food as Future Food: A Review. Der Pharm Lett 2010; 2: 106-116
  • 13 Wildman REC, Bruno RS. Handbook of nutraceuticals and functional foods. New York, USA: CRC Press; 2020
  • 14 Ubaid M, Salauddin N, Shadani MA. et al. Daidzein from Dietary Supplement to a Drug Candidate: An Evaluation of Potential. ACS Omega 2023; 8: 32271-32293
  • 15 Das D, Sarkar S, Bordoloi J. et al. Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes. BioFactors 2018; 44: 407-417
  • 16 Alshehri MM, Sharifi-Rad J, Herrera-Bravo J. et al. Therapeutic Potential of Isoflavones with an Emphasis on Daidzein. Oxid Med Cell Longev 2021; 2021: 6331630
  • 17 Zhang HY, Cui J, Zhang Y. et al. Isoflavones and Prostate Cancer: A Review of Some Critical Issues. Chin Med J (Engl) 2016; 129: 341-347
  • 18 Xie Y, Wang H, He Z. Recent advances in polyphenols improving vascular endothelial dysfunction induced by endogenous toxicity. J Appl Toxicol 2021; 41: 701-712
  • 19 Mendonça Camargo Eduardo P, Possa Abrahao K. Food composition can influence how much alcohol your animal model drinks: A mini-review about the role of isoflavones. Alcohol Clin Exp Res 2022; 46: 6-12
  • 20 Romani AMP. The controversy on the beneficial effect of phytoestrogens in diabetic treatment in postmenopausal women. Biochem Pharmacol 2021; 190: 114619
  • 21 Bhati R, Desai K, Modi N. A critical review on pharmacological and mechanical properties of daidzein. Vidya A J Gujarat Univ 2022; 1: 72-76
  • 22 Zhao W, Shang Z, Li Q. et al. Rapid Screening and Identification of Daidzein Metabolites in Rats Based on UHPLC-LTQ-Orbitrap Mass Spectrometry Coupled with Data-Mining Technologies. Molecules 2018; 23: 151-159
  • 23 Setchell KDR, 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
  • 24 Qin Y, Shu FR, Zeng Y. et al. Daidzein Supplementation Decreases Serum Triglyceride and Uric Acid Concentrations in Hypercholesterolemic Adults with the Effect on Triglycerides Being Greater in Those with the GA Compared with the GG Genotype of ESR-β RsaI. J Nutr 2014; 144: 49-54
  • 25 Raimondi S, Roncaglia L, De Lucia M. et al. Bioconversion of soy isoflavones daidzin and daidzein by Bifidobacterium strains. Appl Microbiol Biotechnol 2009; 81: 943-950
  • 26 Piskula MK. Soy Isoflavone Conjugation Differs in Fed and Food-Deprived Rats. J Nutr 2000; 130: 1766-1771
  • 27 Dwiecki K, Neunert G, Polewski P. et al. Antioxidant activity of daidzein, a natural antioxidant, and its spectroscopic properties in organic solvents and phosphatidylcholine liposomes. J Photochem Photobiol B Biol 2009; 96: 242-248
  • 28 Juliana C, Lister INE, Girsang E. et al. Antioxidant and Elastase Inhibitor from Black Soybean (Glycine max L.) and Its Compound (Daidzein). J Biomed Transl Res 2020; 6: 11-14
  • 29 Li Y, He G, Chen D. et al. Supplementing daidzein in diets improves the reproductive performance, endocrine hormones and antioxidant capacity of multiparous sows. Anim Nutr 2021; 7: 1052-1060
  • 30 Chen W, Ma X, Lin Y. et al. Dietary supplementation with a high dose of daidzein enhances the antioxidant capacity in swine muscle but experts pro-oxidant function in liver and fat tissues. J Anim Sci Biotechnol 2016; 7: 1-11.
  • 31 Hua F, Li CH, Chen XG. et al. Daidzein exerts anticancer activity towards SKOV3 human ovarian cancer cells by inducing apoptosis and cell cycle arrest, and inhibiting the Raf/MEK/ERK cascade. Int J Mol Med 2018; 41: 3485-3492
  • 32 Choi EJ, Kim GH. Antiproliferative activity of daidzein and genistein may be related to ERα/c-erbB-2 expression in human breast cancer cells. Mol Med Rep 2013; 7: 781-784
  • 33 Sattarinezhad E, Fani N, Bordbar AK. et al. Probing the physico-chemical, antioxidant and anticancer influence of β-lactoglobulin on dietary flavonoid daidzein. Informatics Med Unlocked 2021; 25: 100643
  • 34 Ullah MF, Ahmad A, Bhat SH. et al. Simulating hypoxia-induced acidic environment in cancer cells facilitates mobilization and redox-cycling of genomic copper by daidzein leading to pro-oxidant cell death: implications for the sensitization of resistant hypoxic cancer cells to therapeutic c. Biometals 2016; 29: 299-310
  • 35 Cheong SH, Furuhashi K, Ito K. et al. Daidzein promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and improves glucose homeostasis in Type 2 diabetic model mice. J Nutr Biochem 2014; 25: 136-143
  • 36 Cho KW, Lee OH, Banz WJ. et al. Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARgamma transcriptional activity. J Nutr Biochem 2010; 21: 841-847
  • 37 Roghani M, Vaez Mahdavi MR, Jalali-Nadoushan MR. et al. Chronic administration of daidzein, a soybean isoflavone, improves endothelial dysfunction and attenuates oxidative stress in streptozotocin-induced diabetic rats. Phytother Res 2013; 27: 112-117
  • 38 Tan Y, Zhang X, Cheang WS. Isoflavones daidzin and daidzein inhibit lipopolysaccharide-induced inflammation in RAW264.7 macrophages. Chin Med 2022; 17: 1-10
  • 39 Choudhury A, Pai KV. Angiotensin converting enzyme inhibition activity of Daidzein. J Drug Deliv Ther 2014; 4: 92-98
  • 40 Prawez S, Ahanger AA, Singh TU. et al. Chronic administration of phytoestrogen “daidzein” to ameliorate mean arterial pressure and vascular function in N-G-nitro-L-arginine methyl ester hypertensive rats. Vet Arh 2015; 85: 451-464
  • 41 Cao YX, Yang XJ, Liu J. et al. Effects of daidzein sulfates on blood pressure and artery of rats. Basic Clin Pharmacol Toxicol 2006; 99: 425-430
  • 42 Vera R, Galisteo M, Villar IC. et al. Soy isoflavones improve endothelial function in spontaneously hypertensive rats in an estrogen-independent manner: role of nitric-oxide synthase, superoxide, and cyclooxygenase metabolites. J Pharmacol Exp Ther 2005; 314: 1300-1309
  • 43 Takasugi M, Shimada K, Yamada K. et al. Effects of Soybean Isoflavones on the Release of Chemical Mediators from Rat Peritoneal Exudate Cells by Allergic Reaction in Vitro. Food Sci Technol Res 2014; 20: 725-730
  • 44 Fujitaka Y, Hamada H, Uesugi D. et al. Synthesis of Daidzein Glycosides, α-Tocopherol Glycosides, Hesperetin Glycosides by Bioconversion and Their Potential for Anti-Allergic Functional-Foods and Cosmetics. Molecules 2019; 24: 2983
  • 45 Fujitaka Y, Hamada H, Hamada H. et al. Synthesis of Glycosides of α-Tocopherol, Daidzein, Resveratrol, Hesperetin, Naringenin, and Chrysin as Antiallergic Functional Foods and Cosmetics. Nat Prod Commun 2020; 15: 1934578X20944666
  • 46 Shimoda K, Hamada H, Hamada H. Synthesis of Xylooligosaccharides of Daidzein and Their Anti-Oxidant and Anti-Allergic Activities. Int J Mol Sci 2011; 12: 5616-5625
  • 47 Ko WC, Shih CM, Lai YH. et al. Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships. Biochem Pharmacol 2004; 68: 2087-2094
  • 48 Saleem A, Najda A, Mubeen A. et al. HPLC-DAD analysis of Quercus leucotrichophora extract and appraisal of its antiasthmatic potential via modulation of aquaporins, inflammatory, and oxidative stress biomarkers in Albino mice. Biomed Pharmacother 2022; 155: 113702
  • 49 Wei J, Bhatt S, Chang LM. et al. Masilamani M. Isoflavones, Genistein and Daidzein, Regulate Mucosal Immune Response by Suppressing Dendritic Cell Function. PLoS One 2012; 7: e47979
  • 50 Cho CW, Jeong HC, Hong H. et al. Bioconversion of isoflavones during the fermentation of samso-eum with lactobacillus strains. Biotechnol Bioprocess Eng 2012; 17: 1062-1067
  • 51 Soumyakrishnan S, Sudhandiran G. Daidzein attenuates inflammation and exhibits antifibrotic effect against Bleomycin-induced pulmonary fibrosis in Wistar rats. Biomed Prev Nutr 2011; 1: 236-244
  • 52 Soumyakrishnan S, Divya T, Kalayarasan S. et al. Daidzein exhibits anti-fibrotic effect by reducing the expressions of Proteinase activated receptor 2 and TGFβ1/smad mediated inflammation and apoptosis in Bleomycin-induced experimental pulmonary fibrosis. Biochimie 2014; 103: 23-36
  • 53 Kwon DY, Daily JW, Kim HJ. et al. Antidiabetic effects of fermented soybean products on type 2 diabetes. Nutr Res 2010; 30: 1-13
  • 54 Zhang Y, Yuan J, Wang Y. et al. LC-MS/MS determination and pharmacokinetics study of puerarin and daidzein in rat plasma after oral administration of Gegenqinlian decoction and Radix Puerariae extract. Pharmacogn Mag 2014; 10: 241-248
  • 55 Rahman S, Jan G, Jan FG. et al. Phytochemical Screening and Antidiabetic, Antihyperlipidemic, and Antioxidant Effects of Leptopus Cordifolius Decne. In Diabetic Mice. Front Pharmacol 2021; 12: 643242
  • 56 Kader MA, Rahman MM, Mahmud S. et al. A comparative study on the Antihyperlipidemic and antibacterial potency of the shoot and flower extracts of Melastoma malabathricum Linn’s. Clin Phytoscience 2023; 9: 1-12
  • 57 Lin YT, Mao YW, Imtiyaz Z. et al. Comprehensive LC-MS/MS-based phytochemical perspectives and osteogenic effects of Uraria crinita. Food Funct 2020; 11: 5420-5431
  • 58 Meng H, Fu G, Shen J. et al. Ameliorative Effect of Daidzein on Cisplatin-Induced Nephrotoxicity in Mice via Modulation of Inflammation, Oxidative Stress, and Cell Death. Oxid Med Cell Longev 2017; 2017: 3140680
  • 59 Peng Y, Shi Y, Zhang H. et al. Anti-inflammatory and Anti-oxidative Activities of Daidzein and its Sulfonic Acid Ester Derivatives. J Funct Foods 2017; 35: 635-640
  • 60 Liu MH, Lin YS, Sheu SY. et al. Anti-inflammatory effects of daidzein on primary astroglial cell culture. Nutr Neurosci 2009; 12: 123-134
  • 61 Zandi K, Teoh BT, Sam SS. et al. Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol J 2011; 8: 1-11
  • 62 Seo DJ, Jeon SB, Oh H. et al Comparison of the antiviral activity of flavonoids against murine norovirus and feline calicivirus. Food Control 2016; 25-30
  • 63 He Y, Huang M, Tang C. et al. Dietary daidzein inhibits hepatitis C virus replication by decreasing microRNA-122 levels. Virus Res 2021; 298: 198404
  • 64 Chen N, Jiang D, Shao B. et al. Anti-BVDV Activity of Traditional Chinese Medicine Monomers Targeting NS5B (RNA-Dependent RNA Polymerase) In Vitro and In Vivo. Molecules 2023; 28: 3413-3419
  • 65 Buchmann D, Schultze N, Borchardt J. et al. Synergistic antimicrobial activities of epigallocatechin gallate, myricetin, daidzein, gallic acid, epicatechin, 3-hydroxy-6-methoxyflavone and genistein combined with antibiotics against ESKAPE pathogens. J Appl Microbiol 2022; 132: 949-963
  • 66 Undhad T, Hati S, Makwana S. Significance of storage study on ACE inhibitory, antioxidative, antimicrobial activities, and biotransformation of isoflavones of functional fermented soy-based beverage. J Food Process Preserv 2021; 45: e15062
  • 67 Morelli S, Piscioneri A, Guarnieri G. et al. Anti-neuroinflammatory effect of daidzein in human hypothalamic GnRH neurons in an in vitro membrane-based model. BioFactors 2021; 47: 93-111
  • 68 Gottstein N, Ewins BA, Eccleston C. et al. Effect of genistein and daidzein on platelet aggregation and monocyte and endothelial function. Br J Nutr 2003; 89: 607-615
  • 69 Liu YF, Bai YQ, Qi M. Daidzein attenuates abdominal aortic aneurysm through NF-κB, p38MAPK and TGF-β1 pathways. Mol Med Rep 2016; 14: 955-962
  • 70 Ronis MJ, Little JM, Barone GW. et al. Sulfation of the isoflavones genistein and daidzein in human and rat liver and gastrointestinal tract. J Med Food 2006; 9: 348-355
  • 71 Tousen Y, Abe F, Ishida T. et al. Resistant starch promotes equol production and inhibits tibial bone loss in ovariectomized mice treated with daidzein. Metabolism 2011; 60: 1425-1432
  • 72 Deng T, Zhang N, Liu Y. et al. Daidzein ameliorates experimental acute reflux esophagitis in rats via regulation of cytokines. Pharmazie 2021; 76: 84-91
  • 73 Bayer T, Colnot T, Dekant W. Disposition and biotransformation of the estrogenic isoflavone daidzein in rats. Toxicol Sci 2001; 62: 205-211
  • 74 Choi EJ, Kim GH. Hepatoprotective effects of daidzein against 7,12-dimetylbenz[a]anthracene-induced oxidative stress in mice. Int J Mol Med 2009; 23: 659-664
  • 75 Liberation of daidzein by gut microbial β-galactosidase suppresses acetaminophen-induced hepatotoxicity in mice. Cell Host Microbe 2023; 31: 766-780
  • 76 Zhang F, Ru N, Shang ZH. et al. Daidzein ameliorates spinal cord ischemia/reperfusion injury-induced neurological function deficits in Sprague-Dawley rats through PI3K/Akt signaling pathway. Exp Ther Med 2017; 14: 4878-4886
  • 77 Aras AB, Guven M, Akman T. et al. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats. Neural Regen Res 2015; 10: 146-152
  • 78 Hurtado O, Ballesteros I, Cuartero MI. et al. Daidzein has neuroprotective effects through ligand-binding-independent PPARγ activation. Neurochem Int 2012; 61: 119-127
  • 79 Zheng M, Zhou M, Chen M. et al. Neuroprotective Effect of Daidzein Extracted From Pueraria lobate Radix in a Stroke Model Via the Akt/mTOR/BDNF Channel. Front Pharmacol 2022; 12: 772485
  • 80 Kumar NB, Pow-Sang J, Spiess P. et al. A phase II randomized clinical trial using aglycone isoflavones to treat patients with localized prostate cancer in the pre-surgical period prior to radical prostatectomy. Oncotarget 2020; 11: 1218-1234
  • 81 Laddha AP, Murugesan S, Kulkarni YA. In-vivo and in-silico toxicity studies of daidzein: an isoflavone from soy. Drug Chem Toxicol 2022; 45: 1408-1416
  • 82 Karale S, Kamath JV. Effect of daidzein on cisplatin-induced hematotoxicity and hepatotoxicity in experimental rats. Indian J Pharmacol 2017; 49: 49-54
  • 83 Faria W, Martinelli R, Arcas A. et al. Acute and Subacute Toxicity Study on Dietary Supplementation with Soy Isoflavones in Wistar Rats. Curr Nutr Food Sci 2018; 14: 68-78
  • 84 Xiao Y, Mao X, Yu B. et al. Potential risk of isoflavones: toxicological study of daidzein supplementation in piglets. J Agric Food Chem 2015; 63: 4228-4235
  • 85 Schmitt E, Metzler M, Jonas R. et al. Genotoxic activity of four metabolites of the soy isoflavone daidzein. Mutat Res - Genet Toxicol Environ Mutagen 2003; 542: 43-48
  • 86 Aidoo A, Manjanatha MG. Influence of dietary Soy Isoflavones Genistein and Daidzein on Genotoxicity and Mammary Carcinogenicity in Rats Exposed to the Model Carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA). Veg Whole Grains, Their Deriv Cancer Prev 2011; 2: 143-171
  • 87 Matulka RA, Matsuura I, Uesugi T. et al. Developmental and Reproductive Effects of SE5-OH: An Equol-Rich Soy-Based Ingredient. J Toxicol 2009; 2009: 1-13
  • 88 Talsness C, Grote K, Kuriyama S. et al. Prenatal exposure to the phytoestrogen daidzein resulted in persistent changes in ovarian surface epithelial cell height, folliculogenesis, and estrus phase length in adult Sprague-Dawley rat offspring. J Toxicol Environ Health A 2015; 78: 635-644
  • 89 Lamartiniere CA, Wang J, Smith-Johnson M. et al. Daidzein: Bioavailability, Potential for Reproductive Toxicity, and Breast Cancer Chemoprevention in Female Rats. Toxicol Sci 2002; 65: 228-238
  • 90 Singh S, Grewal S, Sharma N. et al. Unveiling the Pharmacological and Nanotechnological Facets of Daidzein: Present State-of-the-Art and Future Perspectives. Molecules 2023; 28: 1774