Articulating the Pharmacological and Nanotechnological Aspects of Genistein: Current and Future Prospectives


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Abstract

Throughout the past several centuries, herbal constituents have been the subject of scientific interest and the latest research into their therapeutic potential is underway. Genistein is a soy-derived isoflavone found in huge amounts in soy, along with the plants of the Fabaceae family. Scientific studies have demonstrated the beneficial effects of genistein on various health conditions. Genistein presents a broad range of pharmacological activities, including anticancer, neuroprotective, cardioprotective, antiulcer, anti-diabetic, wound healing, anti-bacterial, antiviral, skin, and radioprotective effects. However, the hydrophobic nature of genistein results in constrained absorption and restricts its therapeutic potential. In this review, the number of nanocarriers for genistein delivery has been explored, such as polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles, liposomes, micelles, transferosomes, and nanoemulsions and nanofibers. These nano-formulations of genistein have been utilized as a potential strategy for various disorders, employing a variety of ex vivo, in vitro, and in vivo models and various administration routes. This review concluded that genistein is a potential therapeutic agent for treating various diseases, including cancer, neurodegenerative disorders, cardiovascular disorders, obesity, diabetes, ulcers, etc., when formulated in suitable nanocarriers.

About the authors

Keshav Bansal

Institute of Pharmaceutical Research, GLA University

Author for correspondence.
Email: info@benthamscience.net

Vanshita Singh

Institute of Pharmaceutical Research, GLA University

Email: info@benthamscience.net

Samiksha Mishra

Institute of Pharmaceutical Research, GLA University

Email: info@benthamscience.net

Meenakshi Bajpai

Institute of Pharmaceutical Research, GLA University

Email: info@benthamscience.net

References

  1. Rishton, G.M. Natural products as a robust source of new drugs and drug leads: Past successes and present day issues. Am J Cardiol., 2008, 101(10A), 43D-49D. doi: 10.1016/j.amjcard.2008.02.007
  2. Phytochemistry and pharmacology of dalbergia sissoo roxb. Ex DC: A Review. J. Pharm. Pharmacol., 2023, 75(4), 482-501.
  3. Dixon, R.; Ferreira, D. Genistein. Phytochemistry, 2002, 60(3), 205-211. doi: 10.1016/S0031-9422(02)00116-4 PMID: 12031439
  4. Murti, Y.; Agrawal, K.K.; Semwal, B.C.; Gupta, J.; Gupta, R. A review on novel herbal drug delivery system and its application. Curr. Tradit. Med., 2023, 9(2), e280422204154. doi: 10.2174/2215083808666220428092638
  5. Dias, M.C.; Pinto, D.C.G.A.; Silva, A.M.S. Plant flavonoids: Chemical characteristics and biological activity. Molecules, 2021, 26(17), 5377. doi: 10.3390/molecules26175377 PMID: 34500810
  6. Pierzynowska, K.; Gaffke, L.; Jankowska, E.; Rintz, E.; Witkowska, J.; Podlacha, M.; Wiśniewska, K. Proteasome composition and activity changes in cultured fibroblasts derived from mucopolysaccharidoses patients and their modulation by genistein. Front. Cell Dev. Biol., 2020, 8, 1-17.
  7. Pierzynowska, K.; Cyske, Z.; Gaffke, L.; Rintz, E.; Mantej, J.; Podlacha, M.; Wiśniewska, K.; Ĺťabińska, M.; Sochocka, M.; Lorenc, P.; Bielańska, P.; Giecewicz, I.; Węgrzyn, G. Potential of genistein-induced autophagy in the treatment of neurodegenerative diseases. Postepy Biochem., 2021, 67(2), 117-129. PMID: 34378891
  8. Banerjee, S.; Li, Y.; Wang, Z.; Sarkar, F.H. Multi-targeted therapy of cancer by genistein. Cancer Lett., 2008, 269(2), 226-242. doi: 10.1016/j.canlet.2008.03.052 PMID: 18492603
  9. Piotrowska, E.; Jakóbkiewicz-Banecka, J.; Barańska, S.; Tylki-Szymańska, A.; Czartoryska, B.; Węgrzyn, A.; Węgrzyn, G. Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. Eur. J. Hum. Genet., 2006, 14(7), 846-852. doi: 10.1038/sj.ejhg.5201623 PMID: 16670689
  10. Tuli, H.S.; Tuorkey, M.J.; Thakral, F.; Sak, K.; Kumar, M.; Sharma, A.K.; Sharma, U.; Jain, A.; Aggarwal, V.; Bishayee, A. Molecular mechanisms of action of genistein in Cancer: Recent advances. Front. Pharmacol., 2019, 10, 1336. doi: 10.3389/fphar.2019.01336 PMID: 31866857
  11. Bayat, F.; Hosseinpour-Moghadam, R.; Mehryab, F.; Fatahi, Y.; Shakeri, N.; Dinarvand, R.; Ten Hagen, T.L.M.; Haeri, A. Potential application of liposomal nanodevices for non-cancer diseases: An update on design, characterization and biopharmaceutical evaluation. Adv. Colloid Interface Sci., 2020, 277, 102121. doi: 10.1016/j.cis.2020.102121 PMID: 32092487
  12. Daeihamed, M.; Dadashzadeh, S.; Haeri, A.; Akhlaghi, M.F. Potential of liposomes for enhancement of oral drug absorption. Curr. Drug Deliv., 2017, 14(2), 289-303. PMID: 26768542
  13. Sharifi-Rad, J.; Quispe, C.; Imran, M.; Rauf, A.; Nadeem, M.; Gondal, T.A.; Ahmad, B.; Atif, M.; Mubarak, M.S.; Sytar, O.; Zhilina, O.M.; Garsiya, E.R.; Smeriglio, A.; Trombetta, D.; Pons, D.G.; Martorell, M.; Cardoso, S.M.; Razis, A.F.A.; Sunusi, U.; Kamal, R.M.; Rotariu, L.S.; Butnariu, M.; Docea, A.O.; Calina, D. Genistein: An integrative overview of its mode of action, pharmacological properties, and health benefits. Oxid. Med. Cell. Longev., 2021, 2021, 1-36. doi: 10.1155/2021/3268136 PMID: 34336089
  14. Kumar, G.; Virmani, T.; Sharma, A.; Pathak, K. Codelivery of phytochemicals with conventional anticancer drugs in form of nanocarriers. Pharmaceutics, 2023, 15(3), 889. doi: 10.3390/pharmaceutics15030889 PMID: 36986748
  15. Goh, Y.X.; Jalil, J.; Lam, K.W.; Husain, K.; Premakumar, C.M. Genistein: A review on its anti-inflammatory properties. Front. Pharmacol., 2022, 13, 820969. doi: 10.3389/fphar.2022.820969 PMID: 35140617
  16. Jaiswal, N.; Akhtar, J.; Singh, S.P.; Ahsan, F. An overview on genistein and its various formulations. Drug Res., 2019, 69(6), 305-313. doi: 10.1055/a-0797-3657 PMID: 30517965
  17. Coldham, N.G.; Zhang, A.Q.; Key, P.; Sauer, M.J. Absolute bioavailability of 14C genistein in the rat; plasma pharmacokinetics of parent compound, genistein glucuronide and total radioactivity. Eur. J. Drug Metab. Pharmacokinet., 2002, 27(4), 249-258. doi: 10.1007/BF03192335 PMID: 12587954
  18. Shelnutt, S.R.; Cimino, C.O.; Wiggins, P.A.; Ronis, M.J.J.; Badger, T.M. 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(3), 588-594. doi: 10.1093/ajcn/76.3.588 PMID: 12198004
  19. Zhou, S.; Hu, Y.; Zhang, B.; Teng, Z.; Gan, H.; Yang, Z.; Wang, Q.; Huan, M.; Mei, Q. Dose-dependent absorption, metabolism, and excretion of genistein in rats. J. Agric. Food Chem., 2008, 56(18), 8354-8359. doi: 10.1021/jf801051d PMID: 18710250
  20. Ganai, A.A.; Farooqi, H. Bioactivity of genistein: A review of in vitro and in vivo studies. Biomed. Pharmacother., 2015, 76, 30-38. doi: 10.1016/j.biopha.2015.10.026 PMID: 26653547
  21. Hassanpour, S.H.; Dehghani, M. Review of cancer from perspective of molecular. J. Cancer Res. Pract., 2017, 4(4), 127-129. doi: 10.1016/j.jcrpr.2017.07.001
  22. Wang, S.D.; Chen, B.C.; Kao, S.T.; Liu, C.J.; Yeh, C.C. Genistein inhibits tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. BMC Complement. Altern. Med., 2014, 14(1), 26. doi: 10.1186/1472-6882-14-26 PMID: 24433534
  23. Li, Y-S.; Wu, L-P.; Li, K-B.; Liu, Y-P.; Xiang, R.; Zhang, S-B.; Zhu, L-Y.; Zhang, L-Y. Involvement of nuclear factor κB (NF-κB) in the downregulation of cyclooxygenase-2 (COX-2) by genistein in gastric cancer cells. J. Int. Med. Res., 2011, 39(6), 2141-2150. doi: 10.1177/147323001103900610 PMID: 22289529
  24. Huang, W.; Wan, C.; Luo, Q.; Huang, Z.; Luo, Q. Genistein-inhibited cancer stem cell-like properties and reduced chemoresistance of gastric cancer. Int. J. Mol. Sci., 2014, 15(3), 3432-3443. doi: 10.3390/ijms15033432 PMID: 24573253
  25. Zhang, Y.; Chen, H. Genistein attenuates WNT signaling by up-regulating sFRP2 in a human colon cancer cell line. Exp. Biol. Med., 2011, 236(6), 714-722. doi: 10.1258/ebm.2011.010347 PMID: 21571909
  26. Dhandayuthapani, S.; Marimuthu, P.; Hörmann, V.; Kumi-Diaka, J.; Rathinavelu, A. Induction of apoptosis in HeLa cells via caspase activation by resveratrol and genistein. J. Med. Food, 2013, 16(2), 139-146. doi: 10.1089/jmf.2012.0141 PMID: 23356442
  27. Luo, Y.; Wang, S. Apoptotic effect of genistein on human colon cancer cells via inhibiting the nuclear factor-kappa B (NF-KB) pathway. Tumour Biol., 2014, 35(11), 11483-11488. doi: 10.1007/s13277-014-2487-7 PMID: 25128065
  28. Panda, S.P.; Dhurandhar, Y.; Agrawal, M. The interplay of epilepsy with impaired mitophagy and autophagy linked dementia (MAD): A review of therapeutic approaches. Mitochondrion, 2022, 66, 27-37. doi: 10.1016/j.mito.2022.07.002 PMID: 35842181
  29. Pathak, K.; Mishra, S.K.; Porwal, A.; Bahadur, S. Nanocarriers for Alzheimer’s Disease: Research and patent update. J. Appl. Pharm. Sci., 2021, 11(3), 1-21.
  30. Teleanu, R.; Chircov, C.; Grumezescu, A.; Volceanov, A.; Teleanu, D. Antioxidant therapies for neuroprotection—a review. J. Clin. Med., 2019, 8(10), 1659. doi: 10.3390/jcm8101659 PMID: 31614572
  31. Yavarpour-Bali, H.; Ghasemi-Kasman, M.; Pirzadeh, M. Curcumin-loaded nanoparticles: A novel therapeutic strategy in treatment of central nervous system disorders. Int. J. Nanomedicine, 2019, 14, 4449-4460. doi: 10.2147/IJN.S208332 PMID: 31417253
  32. Rumman, M.; Pandey, S.; Singh, B.; Gupta, M.; Ubaid, S.; Mahdi, A.A. Genistein prevents hypoxia-induced cognitive dysfunctions by ameliorating oxidative stress and inflammation in the hippocampus. Neurotox. Res., 2021, 39(4), 1123-1133. doi: 10.1007/s12640-021-00353-x PMID: 33740236
  33. Lu, C.; Lv, J.; Jiang, N.; Wang, H.; Huang, H.; Zhang, L.; Li, S.; Zhang, N.; Fan, B.; Liu, X.; Wang, F. Protective effects of genistein on the cognitive deficits induced by chronic sleep deprivation. Phytother. Res., 2020, 34(4), 846-858. doi: 10.1002/ptr.6567 PMID: 32115816
  34. Pierzynowska, K.; Podlacha, M.; Gaffke, L.; Majkutewicz, I.; Mantej, J.; Węgrzyn, A.; Osiadły, M.; Myślińska, D.; Węgrzyn, G. Autophagy-dependent mechanism of genistein-mediated elimination of behavioral and biochemical defects in the rat model of sporadic Alzheimer’s disease. Neuropharmacology, 2019, 148, 332-346. doi: 10.1016/j.neuropharm.2019.01.030 PMID: 30710571
  35. Gupta, J.; Gupta, R.; Sharma, P. Alzheimer’s Disease: Role of amyloid- β peptide in the pathogenesis of neurodisorder. 2022, 9(7), 7282-7290.
  36. Breijyeh, Z.; Karaman, R. Comprehensive review on Alzheimer’s Disease: Causes and treatment. Molecules, 2020, 25(24), 5789. doi: 10.3390/molecules25245789 PMID: 33302541
  37. Abubakar, M.B.; Sanusi, K.O.; Ugusman, A.; Mohamed, W.; Kamal, H.; Ibrahim, N.H.; Khoo, C.S. Kumar, J. Alzheimer’s Disease: An update and insights into pathophysiology. Front. Aging Neurosci., 2022, 14, 742408. doi: 10.3389/fnagi.2022.742408 PMID: 35431894
  38. Devi, K.P.; Shanmuganathan, B.; Manayi, A.; Nabavi, S.F.; Nabavi, S.M. Molecular and therapeutic targets of genistein in Alzheimer’s Disease. Mol. Neurobiol., 2017, 54(9), 7028-7041. doi: 10.1007/s12035-016-0215-6 PMID: 27796744
  39. Sun, X.; Chen, W.D.; Wang, Y.D. β-Amyloid: the key peptide in the pathogenesis of Alzheimer’s disease. Front. Pharmacol., 2015, 6, 221. doi: 10.3389/fphar.2015.00221 PMID: 26483691
  40. Cai, B.; Ye, S.; Wang, T.; Wang, Y.; Li, J.; Zhan, J.; Shen, G. Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase IV protein levels in Alzheimer’s disease model rats. Neural Regen. Res., 2017, 12(9), 1479-1484. doi: 10.4103/1673-5374.215260 PMID: 29089994
  41. Galvan, A.; Wichmann, T. Pathophysiology of parkinsonism. Clin. Neurophysiol., 2008, 119(7), 1459-1474. doi: 10.1016/j.clinph.2008.03.017 PMID: 18467168
  42. Arbabi, E.; Hamidi, G.; Talaei, S.A.; Salami, M. Estrogen agonist genistein differentially influences the cognitive and motor disorders in an ovariectomized animal model of Parkinsonism. Iran. J. Basic Med. Sci., 2016, 19(12), 1285-1290. PMID: 28096960
  43. Liu, L.X.; Chen, W.F.; Xie, J.X.; Wong, M.S. Neuroprotective effects of genistein on dopaminergic neurons in the mice model of Parkinson’s disease. Neurosci. Res., 2008, 60(2), 156-161. doi: 10.1016/j.neures.2007.10.005 PMID: 18054104
  44. Siddique, Y.H.; Naz, F.; Jyoti, S.; Ali, F. Rahul, Effect of genistein on the transgenic Drosophila model of parkinson’s Disease. J. Diet. Suppl., 2019, 16(5), 550-563. doi: 10.1080/19390211.2018.1472706 PMID: 29969325
  45. Beirão, D.; Monte, H.; Amaral, M.; Longras, A.; Matos, C.; Villas-Boas, F. Depression in adolescence: A review. MECP, 2020, 27(1), 50. doi: 10.1186/s43045-020-00050-z
  46. Chang, M.; Zhang, L.; Dai, H.; Sun, L. Genistein acts as antidepressant agent against chronic mild stress induced depression model of rats through augmentation of brain-derived neurotrophic factor. Brain Behav., 2021, 11(8), e2300. doi: 10.1002/brb3.2300 PMID: 34333865
  47. Rodríguez-Landa, J.F.; Hernández-Figueroa, J.D.; Hernández-Calderón, B.C.; Saavedra, M. Anxiolytic-like effect of phytoestrogen genistein in rats with long-term absence of ovarian hormones in the black and white model. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009, 33(2), 367-372. doi: 10.1016/j.pnpbp.2008.12.024 PMID: 19168113
  48. Aras, A.B.; Guven, M.; Akman, T.; Alacam, H.; Kalkan, Y.; Silan, C.; Cosar, M. Genistein exerts neuroprotective effect on focal cerebral ischemia injury in rats. Inflammation, 2015, 38(3), 1311-1321. doi: 10.1007/s10753-014-0102-0 PMID: 25567369
  49. Sureda, A.; Sanches Silva, A.; Sánchez-Machado, D.I.; López-Cervantes, J.; Daglia, M.; Nabavi, S.F.; Nabavi, S.M. Hypotensive effects of genistein: From chemistry to medicine. Chem. Biol. Interact., 2017, 268, 37-46. doi: 10.1016/j.cbi.2017.02.012 PMID: 28242380
  50. Zhao, L.; Mao, Z.; Brinton, R.D. A select combination of clinically relevant phytoestrogens enhances estrogen receptor beta-binding selectivity and neuroprotective activities in vitro and in vivo. Endocrinology, 2009, 150(2), 770-783. doi: 10.1210/en.2008-0715 PMID: 18818291
  51. Gencel, V.B.; Benjamin, M.M.; Bahou, S.N.; Khalil, R.A. Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease. Mini Rev. Med. Chem., 2012, 12(2), 149-174. doi: 10.2174/138955712798995020 PMID: 22070687
  52. Ambra, R.; Rimbach, G.; de Pascual Teresa, S.; Fuchs, D.; Wenzel, U.; Daniel, H.; Virgili, F. Genistein affects the expression of genes involved in blood pressure regulation and angiogenesis in primary human endothelial cells. Nutr. Metab. Cardiovasc. Dis., 2006, 16(1), 35-43. doi: 10.1016/j.numecd.2005.03.003 PMID: 16399490
  53. Rafieian-Kopaei, M.; Setorki, M.; Doudi, M.; Baradaran, A.; Nasri, H. Atherosclerosis: Process, indicators, risk factors and new hopes. Int. J. Prev. Med., 2014, 5(8), 927-946. PMID: 25489440
  54. Noble, C.; Carlson, K.D.; Neumann, E.; Lewis, B.; Dragomir-Daescu, D.; Lerman, A.; Erdemir, A.; Young, M.D. Finite element analysis in clinical patients with atherosclerosis. J. Mech. Behav. Biomed. Mater., 2022, 125, 104927. doi: 10.1016/j.jmbbm.2021.104927 PMID: 34740008
  55. Lee, C.S.; Kwon, S.J.; Na, S.Y.; Lim, S.P.; Lee, J.H. Genistein supplementation inhibits atherosclerosis with stabilization of the lesions in hypercholesterolemic rabbits. J. Korean Med. Sci., 2004, 19(5), 656-661. doi: 10.3346/jkms.2004.19.5.656 PMID: 15483339
  56. Wang, J.; Zhang, R.; Xu, Y.; Zhou, H.; Wang, B.; Li, S. Genistein inhibits the development of atherosclerosis via inhibiting NFkappaB and VCAM-1 expression in LDLR knockout mice. Can J Physiol Pharmacol, 2008, 86(11), 777-784.
  57. Pulipati, V.P.; Pannain, S. Pharmacotherapy of obesity in complex diseases. Clin. Obes., 2022, 12(1), e12497. doi: 10.1111/cob.12497 PMID: 34889046
  58. Shen, H.H.; Huang, S.Y.; Kung, C.W.; Chen, S.Y.; Chen, Y.F.; Cheng, P.Y.; Lam, K.K.; Lee, Y.M. Genistein ameliorated obesity accompanied with adipose tissue browning and attenuation of hepatic lipogenesis in ovariectomized rats with high-fat diet. J. Nutr. Biochem., 2019, 67, 111-122. doi: 10.1016/j.jnutbio.2019.02.001 PMID: 30884354
  59. Gan, M.; Chen, X.; Chen, Z.; Chen, L.; Zhang, S.; Zhao, Y.; Niu, L.; Li, X.; Shen, L.; Zhu, L. Genistein alleviates high-fat diet-induced obesity by inhibiting the process of gluconeogenesis in mice. Nutrients, 2022, 14(8), 1551. doi: 10.3390/nu14081551 PMID: 35458112
  60. Liu, D.; Zhen, W.; Yang, Z.; Carter, J.D.; Si, H.; Reynolds, K.A. Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes, 2006, 55(4), 1043-1050. doi: 10.2337/diabetes.55.04.06.db05-1089 PMID: 16567527
  61. Yu, M.; Chen, X.; Liu, J.; Ma, Q.; Zhuo, Z.; Chen, H.; Zhou, L.; Yang, S.; Zheng, L.; Ning, C.; Xu, J.; Gao, T.; Hou, S.T. Gallic acid disruption of Aβ1–42 aggregation rescues cognitive decline of APP/PS1 double transgenic mouse. Neurobiol. Dis., 2019, 124, 67-80. doi: 10.1016/j.nbd.2018.11.009 PMID: 30447302
  62. Olokoba, A.B.; Obateru, O.A.; Olokoba, L.B. Type 2 diabetes mellitus: A review of current trends. Oman Med. J., 2012, 27(4), 269-273. doi: 10.5001/omj.2012.68 PMID: 23071876
  63. Elmarakby, A.A.; Ibrahim, A.S.; Faulkner, J.; Mozaffari, M.S.; Liou, G.I.; Abdelsayed, R. Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin-induced diabetic mice. Vascul. Pharmacol., 2011, 55(5-6), 149-156. doi: 10.1016/j.vph.2011.07.007 PMID: 21807121
  64. Park, Y.J.; Ko, J.; Jeon, S.; Kwon, Y. Protective effect of genistein against neuronal degeneration in ApoE−/− mice fed a high-fat diet. Nutrients, 2016, 8(11), 692. doi: 10.3390/nu8110692 PMID: 27809235
  65. Li, R.; Ding, X.W.; Geetha, T.; Al-Nakkash, L.; Broderick, T.L.; Babu, J.R. Beneficial effect of genistein on diabetes-induced brain damage in the ob/ob mouse model. Drug Des. Devel. Ther., 2020, 14, 3325-3336. doi: 10.2147/DDDT.S249608 PMID: 32884237
  66. Zhang, T.; Chi, X.X. The effect of genistein on lipid levels and LDLR, LXRα and ABCG1 expression in postmenopausal women with hyperlipidemia. Diabetol. Metab. Syndr., 2019, 11(1), 111. doi: 10.1186/s13098-019-0507-x
  67. Perumal, D.; Adhimoolam, M.; Ivan, E.; Rajamohammed, M. Effects of soy isoflavone genistein on lipid profile and hepatic steatosis in high-fat-fed Wistar rats. Natl. J. Physiol. Pharm. Pharmacol., 2019, 9(0), 1. doi: 10.5455/njppp.2019.9.0621617062019
  68. Deng, X.; Gould, M.; Ali, M.A. A review of current advancements for wound healing: Biomaterial applications and medical devices. J. Biomed. Mater. Res. B Appl. Biomater., 2022, 110(11), 2542-2573. doi: 10.1002/jbm.b.35086 PMID: 35579269
  69. Čoma, M.; Lachová, V; Mitrengová, P; Gál, P Molecular changes underlying genistein treatment of wound healing: A review. Curr. Issues Mol. Biol., 2021, 43(1), 127-141. doi: 10.3390/cimb43010011 PMID: 34067763
  70. Park, E.; Lee, S.M.; Jung, I.K.; Lim, Y.; Kim, J.H. Effects of genistein on early-stage cutaneous wound healing. Biochem. Biophys. Res. Commun., 2011, 410(3), 514-519. doi: 10.1016/j.bbrc.2011.06.013 PMID: 21679688
  71. Eo, H.; Lee, H.J.; Lim, Y. Ameliorative effect of dietary genistein on diabetes induced hyper-inflammation and oxidative stress during early stage of wound healing in alloxan induced diabetic mice. Biochem. Biophys. Res. Commun., 2016, 478(3), 1021-1027. doi: 10.1016/j.bbrc.2016.07.039 PMID: 27431618
  72. Hwang, K.; Chung, R.S.; Schmitt, J.M.; Buck, D.; Winn, S.R.; Hollinger, J.O. The effect of topical genistein on soft tissue wound healing in rats. J. Histotechnol., 2001, 24(2), 95-99. doi: 10.1179/his.2001.24.2.95
  73. Pawar, R.S.; Patil, U.K.; Gadekar, R.; Singour, P.K.; Chaurasiya, P.K. A potential of some medicinal plants as an antiulcer agents. Pharmacogn. Rev., 2010, 4(8), 136-146. doi: 10.4103/0973-7847.70906 PMID: 22228953
  74. Hegab, I.I.; Abd-Ellatif, R.N.; Sadek, M.T. The gastroprotective effect of N -acetylcysteine and genistein in indomethacin-induced gastric injury in rats. Can. J. Physiol. Pharmacol., 2018, 96(11), 1161-1170. doi: 10.1139/cjpp-2017-0730 PMID: 30011378
  75. Siriviriyakul, P.; Werawatganon, D.; Phetnoo, N.; Somanawat, K.; Chatsuwan, T.; Klaikeaw, N.; Chayanupatkul, M. Genistein attenuated gastric inflammation and apoptosis in Helicobacter pylori-induced gastropathy in rats. BMC Gastroenterol., 2020, 20(1), 410. doi: 10.1186/s12876-020-01555-x PMID: 33297977
  76. Abdel-raheem, I.T.; Bamagous, G.; Omran, G. Anti-ulcerogenic effect of genistein against indomethacin-induced gastric ulcer in rats. Asian J Pharm Clin Res, 2016, 9(2)
  77. Salvati, A.L.; De Dominicis, A.; Tait, S.; Canitano, A.; Lahm, A.; Fiore, L. Mechanism of action at the molecular level of the antiviral drug 3(2H)-isoflavene against type 2 poliovirus. Antimicrob. Agents Chemother., 2004, 48(6), 2233-2243. doi: 10.1128/AAC.48.6.2233-2243.2004 PMID: 15155227
  78. Andres, A.; Donovan, S.M.; Kuhlenschmidt, M.S. Soy isoflavones and virus infections. J. Nutr. Biochem., 2009, 20(8), 563-569. doi: 10.1016/j.jnutbio.2009.04.004 PMID: 19596314
  79. Arabyan, E.; Hakobyan, A.; Kotsinyan, A.; Karalyan, Z.; Arakelov, V.; Arakelov, G.; Nazaryan, K.; Simonyan, A.; Aroutiounian, R.; Ferreira, F.; Zakaryan, H. Genistein inhibits African swine fever virus replication in vitro by disrupting viral DNA synthesis. Antiviral Res., 2018, 156, 128-137. doi: 10.1016/j.antiviral.2018.06.014 PMID: 29940214
  80. Guo, X. Antibacterial and anti-inflammatory effects of genistein in Staphylococcus aureus induced osteomyelitis in rats. J. Biochem. Mol. Toxicol., 2023, 37(4), e23298. doi: 10.1002/jbt.23298 PMID: 36727417
  81. Terra, V.A.; Souza-Neto, F.P.; Frade, M.A.C.; Ramalho, L.N.Z.; Andrade, T.A.M.; Pasta, A.A.C.; Conchon, A.C.; Guedes, F.A.; Luiz, R.C.; Cecchini, R.; Cecchini, A.L. Genistein prevents ultraviolet B radiation-induced nitrosative skin injury and promotes cell proliferation. J. Photochem. Photobiol. B, 2015, 144, 20-27. doi: 10.1016/j.jphotobiol.2015.01.013 PMID: 25668145
  82. Jahan, A.; Akhtar, J. Recapitulate genistein for topical applications including nanotechnology delivery. Inorg. Nano-Met. Chem, 2021, 52(9), 1306-1317.
  83. Berbee, M.; Fu, Q.; Boerma, M.; Pathak, R.; Zhou, D.; Kumar, K.S.; Hauer-Jensen, M. Reduction of radiation-induced vascular nitrosative stress by the vitamin E analog γ-tocotrienol: evidence of a role for tetrahydrobiopterin. Int. J. Radiat. Oncol. Biol. Phys., 2011, 79(3), 884-891. doi: 10.1016/j.ijrobp.2010.08.032 PMID: 20950957
  84. Hanedan Uslu, G.; Canyilmaz, E.; Serdar, L.; Ersöz, Ş. Protective effects of genistein and melatonin on mouse liver injury induced by whole-body ionising radiation. Mol. Clin. Oncol., 2019, 10(2), 261-266. PMID: 30680205
  85. Kim, J.S.; Heo, K.; Yi, J.M.; Gong, E.J.; Yang, K.; Moon, C.; Kim, S.H. Genistein mitigates radiation-induced testicular injury. Phytother. Res., 2012, 26(8), 1119-1125. doi: 10.1002/ptr.3689 PMID: 22162311
  86. Bonferoni, M.; Rossi, S.; Sandri, G.; Ferrari, F.; Gavini, E.; Rassu, G.; Giunchedi, P. Nanoemulsions for "nose-to-brain" drug delivery. Pharmaceutics, 2019, 11(2), 84. doi: 10.3390/pharmaceutics11020084 PMID: 30781585
  87. Brannon-Peppas, L.; Blanchette, J.O. Nanoparticle and targeted systems for cancer therapy. Adv. Drug Deliv. Rev., 2004, 56(11), 1649-1659. doi: 10.1016/j.addr.2004.02.014 PMID: 15350294
  88. Kayser, O.; Lemke, A.; Hernández-Trejo, N. The impact of nanobiotechnology on the development of new drug delivery systems. Curr. Pharm. Biotechnol., 2005, 6(1), 3-5. doi: 10.2174/1389201053167158 PMID: 15727551
  89. Yeligar, R.R.; Sarwa, K.K.; Chandrakar, M.; Jangde, M.S. Nanotechnology-based delivery of genistein to overcome physicochemical hindrance and enhance therapeutic response in skin cancer. BioNanoSci., 2023, 13, 1339-1358.
  90. George, A.; Shah, P.A.; Shrivastav, P.S. Natural biodegradable polymers based nano-formulations for drug delivery: A review. Int. J. Pharm., 2019, 561, 244-264. doi: 10.1016/j.ijpharm.2019.03.011 PMID: 30851391
  91. Zhang, T.; Wang, H.; Ye, Y.; Zhang, X.; Wu, B. Micellar emulsions composed of mPEG-PCL/MCT as novel nanocarriers for systemic delivery of genistein: A comparative study with micelles. Int. J. Nanomedicine, 2015, 10, 6175-6184. PMID: 26491290
  92. Xiao, Y.; Ho, C-.T.; Chen, Y.; Wang, Y.; Wei, Z.; Dong, M.; Huang, Q. Synthesis, characterization, and evaluation of genisteinloaded zein/carboxymethyl chitosan nanoparticles with improved water dispersibility, enhanced antioxidant activity, and controlled release property. Foods, 2020, 9(11), 1-26.
  93. Langasco, R.; Fancello, S.; Rassu, G.; Cossu, M.; Cavalli, R.; Galleri, G.; Giunchedi, P.; Migheli, R.; Gavini, E. Increasing protective activity of genistein by loading into transfersomes: A new potential adjuvant in the oxidative stress-related neurodegenerative diseases? Phytomedicine, 2019, 52, 23-31. doi: 10.1016/j.phymed.2018.09.207 PMID: 30599903
  94. Ravikumara, N.R.; Madhusudhan, B. Fabrication and characterization of genistein encapsulated poly (D, L) lactic acid nanoparticles for pharmaceutical application. Curr. Nanosci., 2013, 9(2), 293-302. doi: 10.2174/1573413711309020021
  95. Patra, A.; Satpathy, S.; Naik, P.K.; Kazi, M.; Hussain, M.D. Folate receptor-targeted PLGA-PEG nanoparticles for enhancing the activity of genistein in ovarian cancer. Artif. Cells Nanomed. Biotechnol., 2022, 50(1), 228-239. doi: 10.1080/21691401.2022.2118758 PMID: 36330543
  96. Tang, J.; Xu, N.; Ji, H.; Liu, H.; Wang, Z.; Wu, L. Eudragit nanoparticles containing genistein: Formulation, development, and bioavailability assessment. Int. J. Nanomedicine, 2011, 6, 2429-2435. PMID: 22072878
  97. Bakhsh, S.; Khan, B.A.; Safdar, M.; Alam, S.; Ramzan, M.; Rashid, S.A.; Tariq, M.; Anwer, Z.; Ahmad, N. Formulation, development, evaluation, and characterization of chitosan-pgapec nanoparticles containing genistein. Lat. Am. J. Pharm., 2016, 35(9), 1913-1921.
  98. Botet-Carreras, A.; Tamames-Tabar, C.; Salles, F.; Rojas, S.; Imbuluzqueta, E.; Lana, H.; Blanco-Prieto, M.J.; Horcajada, P. Improving the genistein oral bioavailability via its formulation into the metal–organic framework MIL-100(Fe). J. Mater. Chem. B Mater. Biol. Med., 2021, 9(9), 2233-2239. doi: 10.1039/D0TB02804E PMID: 33596280
  99. Zhang, H.; Liu, G.; Zeng, X.; Wu, Y.; Yang, C.; Mei, L.; Wang, Z.; Huang, L. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells. Int. J. Nanomedicine, 2015, 10, 2461-2473. PMID: 25848264
  100. Rassu, G.; Porcu, E.; Fancello, S.; Obinu, A.; Senes, N.; Galleri, G.; Migheli, R.; Gavini, E.; Giunchedi, P. Intranasal delivery of genistein-loaded nanoparticles as a potential preventive system against neurodegenerative disorders. Pharmaceutics, 2018, 11(1), 8. doi: 10.3390/pharmaceutics11010008 PMID: 30597930
  101. Patel, N.V.; Sheth, N.R.; Mohddesi, B. Formulation and evaluation of genistein – a novel isoflavone loaded chitosan and eudragit® nanoparticles for cancer therapy. Mater. Today Proc., 2015, 2(9), 4477-4482. doi: 10.1016/j.matpr.2015.10.055
  102. Scioli Montoto, S.; Muraca, G.; Ruiz, M.E. Solid lipid nanoparticles for drug delivery: Pharmacological and biopharmaceutical aspects. Front. Mol. Biosci., 2020, 7, 587997. doi: 10.3389/fmolb.2020.587997 PMID: 33195435
  103. Das, S.; Chaudhury, A. Recent advances in lipid nanoparticle formulations with solid matrix for oral drug delivery. AAPS PharmSciTech, 2011, 12(1), 62-76. doi: 10.1208/s12249-010-9563-0 PMID: 21174180
  104. Obinu, A.; Burrai, G.P.; Cavalli, R.; Galleri, G.; Migheli, R.; Antuofermo, E.; Rassu, G.; Gavini, E.; Giunchedi, P. Transmucosal solid lipid nanoparticles to improve genistein absorption via intestinal lymphatic transport. Pharmaceutics, 2021, 13(2), 267. doi: 10.3390/pharmaceutics13020267 PMID: 33669306
  105. Kim, J.T.; Barua, S.; Kim, H.; Hong, S.C.; Yoo, S.Y.; Jeon, H.; Cho, Y.; Gil, S.; Oh, K.; Lee, J. Absorption study of genistein using solid lipid microparticles and nanoparticles: Control of oral bioavailability by particle sizes. Biomol. Ther., 2017, 25(4), 452-459. doi: 10.4062/biomolther.2017.095 PMID: 28605834
  106. Patel, P.; Patel, M. Nanostructured lipid carriers- a versatile carrier for oral delivery of lipophilic drugs. Recent Pat. Nanotechnol., 2021, 15(2), 154-164. doi: 10.2174/1872210514666200909154959 PMID: 32912129
  107. Talegaonkar, S.; Bhattacharyya, A. Potential of lipid nanoparticles (SLNs and NLCs) in enhancing oral bioavailability of drugs with poor intestinal permeability. AAPS PharmSciTech, 2019, 20(3), 121. doi: 10.1208/s12249-019-1337-8 PMID: 30805893
  108. Mittal, P.; Vrdhan, H.; Ajmal, G.; Bonde, G.; Kapoor, R.; Mishra, B. Formulation and characterization of genistein-loaded nanostructured lipid carriers: pharmacokinetic, biodistribution and In vitro cytotoxicity studies. Curr. Drug Deliv., 2019, 16(3), 215-225. doi: 10.2174/1567201816666181120170137 PMID: 30465502
  109. Liu, J.L.; Zhang, W.J.; Li, X.D.; Yang, N.; Pan, W.S.; Kong, J.; Zhang, J.S. Sustained-release genistein from nanostructured lipid carrier suppresses human lens epithelial cell growth. Int. J. Ophthalmol., 2016, 9(5), 643-649. doi: 10.18240/ijo.2021.05.02 PMID: 27275415
  110. Dewangan, H.K.; Maurya, L.; Soni, S.; Singh, S. Genistein loaded long circulating nanostructured lipid carriers: Optimization, evaluation and delivery to meloma cells for treatment of cancer. SSRN, 2022. doi: 10.2139/ssrn.3999218
  111. Witika, B.A.; Mweetwa, L.L.; Tshiamo, K.O.; Edler, K.; Matafwali, S.K.; Ntemi, P.V.; Chikukwa, M.T.R.; Makoni, P.A. Vesicular drug delivery for the treatment of topical disorders: Current and future perspectives. J. Pharm. Pharmacol., 2021, 73(11), 1427-1441. doi: 10.1093/jpp/rgab082 PMID: 34132342
  112. Liu, P.; Chen, G.; Zhang, J. A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules, 2022, 27(4), 1372. doi: 10.3390/molecules27041372 PMID: 35209162
  113. Andra, V.V.S.N.L.; Pammi, S.V.N.; Bhatraju, L.V.K.P.; Ruddaraju, L.K. A comprehensive review on novel liposomal methodologies, commercial formulations, clinical trials and patents. Bionanoscience, 2022, 12(1), 274-291. doi: 10.1007/s12668-022-00941-x PMID: 35096502
  114. Phan, V.; Walters, J.; Brownlow, B.; Elbayoumi, T. Enhanced cytotoxicity of optimized liposomal genistein via specific induction of apoptosis in breast, ovarian and prostate carcinomas. J. Drug Target., 2013, 21(10), 1001-1011. doi: 10.3109/1061186X.2013.847099 PMID: 24151835
  115. Song, X.; Gan, K.; Qin, S.; Chen, L.; Liu, X.; Chen, T.; Liu, H. Preparation and characterization of general-purpose gelatin-based co-loading flavonoids nano-core structure. Sci. Rep., 2019, 9(1), 6365. doi: 10.1038/s41598-019-42909-0 PMID: 31019215
  116. Lopes de Azambuja, C.R.; dos Santos, L.G.; Rodrigues, M.R.; Rodrigues, R.F.M.; da Silveira, E.F.; Azambuja, J.H.; Flores, A.F.C.; Horn, A.P.; Dora, C.L.; Muccillo-Baisch, A.L.; Braganhol, E.; da Silva Pinto, L.; Parize, A.L.; de Lima, V.R. 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, 2015, 193, 24-35. doi: 10.1016/j.chemphyslip.2015.10.001 PMID: 26453973
  117. Tian, J.; Guo, F.; Chen, Y.; Li, Y.; Yu, B.; Li, Y. Nanoliposomal formulation encapsulating celecoxib and genistein inhibiting COX-2 pathway and Glut-1 receptors to prevent prostate cancer cell proliferation. Cancer Lett., 2019, 448, 1-10. doi: 10.1016/j.canlet.2019.01.002 PMID: 30673592
  118. Tian, J.; Chi, C.; Bian, G.; Xing, D.; Guo, F.; Wang, X. PSMA conjugated combinatorial liposomal formulation encapsulating genistein and plumbagin to induce apoptosis in prostate cancer cells. Colloids Surf. B Biointerfaces, 2021, 203, 111723. doi: 10.1016/j.colsurfb.2021.111723 PMID: 33839474
  119. Komeil, I.A.; El-Refaie, W.M.; Gowayed, M.A.; El-Ganainy, S.O.; El Achy, S.N.; Huttunen, K.M.; Abdallah, O.Y. Oral genistein-loaded phytosomes with enhanced hepatic uptake, residence and improved therapeutic efficacy against hepatocellular carcinoma. Int. J. Pharm., 2021, 601, 120564. doi: 10.1016/j.ijpharm.2021.120564 PMID: 33812970
  120. Perumal, S.; Atchudan, R.; Lee, W. A review of polymeric micelles and their applications. Polymers, 2022, 14(12), 2510. doi: 10.3390/polym14122510 PMID: 35746086
  121. Barbosa-Barros, L.; Barba, C.; Rodríguez, G.; Cócera, M.; Coderch, L.; López-Iglesias, C.; de la Maza, A.; López, O. Lipid nanostructures: Self-assembly and effect on skin properties. Mol. Pharm., 2009, 6(4), 1237-1245. doi: 10.1021/mp9000734 PMID: 19432456
  122. Cheng, Q.; Qin, W.; Yu, Y.; Li, G.; Wu, J.; Zhuo, L. Preparation and characterization of PEG-PLA genistein micelles using a modified emulsion-evaporation method. J. Nanomater., 2020, 2020, 1-15. doi: 10.1155/2020/3278098
  123. Shen, H.; He, D.; Wang, S.; Ding, P.; Wang, J.; Ju, J. Preparation, characterization, and pharmacokinetics study of a novel genistein-loaded mixed micelles system. Drug Dev. Ind. Pharm., 2018, 44(9), 1536-1542. doi: 10.1080/03639045.2018.1483384 PMID: 29848136
  124. Kwon, S.H.; Kim, S.Y.; Ha, K.W.; Kang, M.J.; Huh, J.S.; Tae Jong, I.; Kim, Y.M.; Park, Y.M.; Kang, K.H.; Lee, S.; Chang, J.Y.; Lee, J.; Choi, Y.W. Pharmaceutical evaluation of genistein-loaded pluronic micelles for oral delivery. Arch. Pharm. Res., 2007, 30(9), 1138-1143. doi: 10.1007/BF02980249 PMID: 17958332
  125. Hou, Y.; Xin, M.; Li, Q.; Wu, X. Glycyrrhizin micelle as a genistein nanocarrier: Synergistically promoting corneal epithelial wound healing through blockage of the HMGB1 signaling pathway in diabetic mice. Exp. Eye Res., 2021, 204, 108454. doi: 10.1016/j.exer.2021.108454 PMID: 33497689
  126. Opatha, S.A.T.; Titapiwatanakun, V.; Chutoprapat, R. Transfersomes: A promising nanoencapsulation technique for transdermal drug delivery. Pharmaceutics, 2020, 12(9), 855. doi: 10.3390/pharmaceutics12090855 PMID: 32916782
  127. Benson, H.A.E. Transfersomes for transdermal drug delivery. Expert Opin. Drug Deliv., 2006, 3(6), 727-737. doi: 10.1517/17425247.3.6.727 PMID: 17076595
  128. Che Marzuki, N.H.; Wahab, R.A.; Abdul Hamid, M.; Hamid, M.A. An overview of nanoemulsion: Concepts of development and cosmeceutical applications. Biotechnol. Biotechnol. Equip., 2019, 33(1), 779-797. doi: 10.1080/13102818.2019.1620124
  129. Dinshaw, I.J.; Ahmad, N.; Salim, N.; Leo, B.F. Nanoemulsions: A review on the conceptualization of treatment for psoriasis using a ‘green’ surfactant with low-energy emulsification method. Pharmaceutics, 2021, 13(7), 1024. doi: 10.3390/pharmaceutics13071024 PMID: 34371716
  130. Silva, A.P.C.; Nunes, B.R.; De Oliveira, M.C.; Koester, L.S.; Mayorga, P.; Bassani, V.L.; Teixeira, H.F. Development of topical nanoemulsions containing the isoflavone genistein. Pharmazie, 2009, 64(1), 32-35. PMID: 19216228
  131. de Vargas, B.A.; Bidone, J.; Oliveira, L.K.; Koester, L.S.; Bassani, V.L.; Teixeira, H.F. Development of topical hydrogels containing genistein-loaded nanoemulsions. J. Biomed. Nanotechnol., 2012, 8(2), 330-336. doi: 10.1166/jbn.2012.1386 PMID: 22515085
  132. Huang, Z.M.; Zhang, Y.Z.; Kotaki, M.; Ramakrishna, S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Compos. Sci. Technol., 2003, 63(15), 2223-2253. doi: 10.1016/S0266-3538(03)00178-7
  133. Ismail, M.; Ibrahim, S.; El-Amir, A. EL-Rafei, A.; Allam, N.; Abdellatif, A. Genistein loaded nanofibers protect spinal cord tissue following experimental injury in rats. Biomedicines, 2018, 6(4), 96. doi: 10.3390/biomedicines6040096 PMID: 30287760
  134. Landauer, M.R.; Harvey, A.J.; Kaytor, M.D.; Day, R.M. Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome. J. Radiat. Res., 2019, 60(3), 308-317. doi: 10.1093/jrr/rrz014 PMID: 31038675
  135. Kaytor, M.D.; Serebrenik, A.A.; Lapanowski, K.; McFall, D.; Jones, M.; Movsas, B.; Simone, C.B., II; Brown, S.L. The radioprotectant nano-genistein enhances radiotherapy efficacy of lung tumors in mice. Transl. Lung Cancer Res., 2023, 12(5), 999-1010. doi: 10.21037/tlcr-22-856 PMID: 37323169
  136. Wacker, M.G.; Proykova, A.; Santos, G.M.L. Dealing with nanosafety around the globe—Regulation vs. innovation. Int. J. Pharm., 2016, 509(1-2), 95-106. doi: 10.1016/j.ijpharm.2016.05.015 PMID: 27184102
  137. Ventola, C.L. Progress in nanomedicine: Approved and investigational nanodrugs. P&T, 2017, 42(12), 742-755. PMID: 29234213
  138. Grossman, J.H.; Crist, R.M.; Clogston, J.D. Early development challenges for drug products containing nanomaterials. AAPS J., 2017, 19(1), 92-102. doi: 10.1208/s12248-016-9980-4 PMID: 27612680
  139. Liggins, J.; Bluck, L.J.C.; Runswick, S.; Atkinson, C.; Coward, W.A.; Bingham, S.A. Daidzein and genistein contents of vegetables. Br. J. Nutr., 2000, 84(5), 717-725. doi: 10.1017/S0007114500002075 PMID: 11177186
  140. Liggins, J.; Bluck, L.J.C.; Runswick, S.; Atkinson, C.; Coward, W.A.; Bingham, S.A. Daidzein and genistein content of fruits and nuts. J. Nutr. Biochem., 2000, 11(6), 326-331. doi: 10.1016/S0955-2863(00)00085-1 PMID: 11002128
  141. Ahmad, S.; Pathak, D.K. Nutritional changes in soybean during germination. J. Food Sci. Technol., 2000, 37(6), 665-666.
  142. Quinhone, A.; Ida, E.I. 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. doi: 10.1016/j.foodchem.2014.06.012 PMID: 25053043

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