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Review Articles

Unveiling the neuroprotective properties of isoflavones: current evidence, molecular mechanisms and future perspectives

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References

  • Abbruzzese, G., J. Morón-Oset, S. Díaz-Castroverde, N. García-Font, C. Roncero, F. López-Muñoz, J. L. Marco Contelles, and M. J. Oset-Gasque. 2020. Neuroprotection by phytoestrogens in the model of deprivation and resupply of oxygen and glucose in vitro: The contribution of autophagy and related signaling mechanisms. Antioxidants 9 (6):545. doi: 10.3390/antiox9060545.
  • Abdou, H. M., M. I. Yousef, D. A. El Mekkawy, and A. S. Al-Shami. 2016. Prophylactic neuroprotective efficiency of co-administration of Ginkgo biloba and Trifolium pretense against sodium arsenite-induced neurotoxicity and dementia in different regions of brain and spinal cord of rats. Food and Chemical Toxicology 94:112–27. doi: 10.1016/j.fct.2016.05.015.
  • Adams, S. M., M. V. Aksenova, M. Y. Aksenov, C. F. Mactutus, and R. M. Booze. 2012. Soy Isoflavones Genistein and Daidzein Exert Anti-Apoptotic Actions via a Selective ER-mediated Mechanism in Neurons following HIV-1 Tat1-86 Exposure. PloS one 7 (5): E 37540. doi: 10.1371/journal.pone.0037540.
  • Ajeigbe, O. F., G. Oboh, A. O. Ademosun, and A. A. Oyagbemi. 2021. Ficus asperifolia Miq-enriched biscuit diet protects against L-NAME induced hyperlipidemia and hypertension in rats. Food Frontiers 3 (1):150–60. doi: 10.1002/fft2.101.
  • Akhlaghi, M., M. Zare, and F. Nouripour. 2017. Effect of soy and soy isoflavones on obesity-related anthropometric measures: A systematic review and meta-analysis of randomized controlled clinical trials. Advances in Nutrition 8 (5):705–17. doi: 10.3945/an.117.015370.
  • Al-Abbasi, F. A. 2022. Neuroprotective effect of butin against rotenone-induced Parkinson’s disease mediated by antioxidant and anti-inflammatory actions through paraoxonase-1-induction. Journal of Taibah University for Science 16 (1):944–53. doi: 10.1080/16583655.2022.2128561.
  • Al-Shami, A. S., A. E. Essawy, and H. T. A. E. A. Elkader. 2023. Molecular mechanisms underlying the potential neuroprotective effects of Trifolium pratense and its phytoestrogen-isoflavones in neurodegenerative disorders. Phytotherapy Research 37 (6):2693–737. doi: 10.1002/ptr.7870.
  • Aldhahri, R. S., B. S. Alghamdi, N. A. Alzahrani, K. A. Bahaidrah, H. M. Alsufiani, R. A. Mansouri, and G. M. Ashraf. 2022. Biochanin A improves memory decline and brain pathology in cuprizone-induced mouse model of multiple sclerosis. Behavioral Sciences 12 (3):70. doi: 10.3390/bs12030070.
  • Alipour, M. R., and E. Karimi-Sales. 2020. Molecular mechanisms of protective roles of isoflavones against chemicals-induced liver injuries. Chemico-Biological Interactions 329:109213. doi: 10.1016/j.cbi.2020.109213.
  • Alizadeh, A., S. M. Dyck, and S. Karimi-Abdolrezaee. 2019. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms. Frontiers in Neurology 10:282– doi: 10.3389/fneur.2019.00282.
  • Amrouche, T. A., X. Yang, E. Capanoglu, W. Huang, Q. Chen, L. Wu, Y. Zhu, Y. Liu, Y. Wang, and B. Lu. 2022. Contribution of edible flowers to the Mediterranean diet: Phytonutrients, bioactivity evaluation and applications. Food Frontiers 3 (4):592–630. doi: 10.1002/fft2.142.
  • An, J., C. Tzagarakis-Foster, T. C. Scharschmidt, N. Lomri, and D. C. Leitman. 2001. Estrogen receptor β-selective transcriptional activity and recruitment of coregulators by phytoestrogens. The Journal of Biological Chemistry 276 (21):17808–14. doi: 10.1074/jbc.M100953200.
  • Andres, A., S. M. Donovan, and M. S. Kuhlenschmidt. 2009. Soy isoflavones and virus infections. The Journal of Nutritonal Biochemistry 20:563–9.
  • Arai, Y., M. Uehara, Y. Sato, M. Kimira, A. Eboshida, H. Adlercreutz, and S. Watanabe. 2000. Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake. Journal of Epidemiology 10 (2):127–35. doi: 10.2188/jea.10.127.
  • Aras, A. B., M. Guven, T. Akman, A. Ozkan, H. M. Sen, U. Duz, Y. Kalkan, C. Silan, and M. Cosar. 2015. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats. Neural Regeneration Research 10 (1):146–52. doi: 10.4103/1673-5374.150724.
  • Arbabi, E., G. Hamidi, S. A. Talaei, and M. Salami. 2016. Estrogen agonist genistein differentially influences the cognitive and motor disorders in an ovariectomized animal model of Parkinsonism. Iranian Journal of Basic Medical Sciences 19:1285–90.
  • Arcos-Burgos, M., F. Lopera, D. Sepulveda-Falla, and C. Mastronardi. 2019. Neural plasticity during aging. Neural Plasticity 2019:6042132–3. doi: 10.1155/2019/6042132.
  • Ariyani, W., W. Miyazaki, and N. Koibuchi. 2019. A novel mechanism of S-equol action in neurons and astrocytes: The possible involvement of GPR30/GPER1. International Journal of Molecular Sciences 20 (20):5178. doi: 10.3390/ijms20205178.
  • Arnal, J.-F., F. Lenfant, R. Metivier, G. Flouriot, D. Henrion, M. Adlanmerini, C. Fontaine, P. Gourdy, P. Chambon, B. Katzenellenbogen, et al. 2017. Membrane and nuclear estrogen receptor alpha actions: From Tissue specificity to medical implications. Physiological Reviews 97 (3):1045–87. doi: 10.1152/physrev.00024.2016.
  • Bagheri, M., M. Roghani, M.-T. Joghataei, and S. Mohseni. 2012. Genistein inhibits aggregation of exogenous amyloid-beta1-40 and alleviates astrogliosis in the hippocampus of rats. Brain Research 1429:145–54. doi: 10.1016/j.brainres.2011.10.020.
  • Barbosa, C. D., J. G. Costa, J. S. Giolo, L. T. Rossato, P. C. Nahas, I. M. Mariano, J. P. Batista, G. M. Puga, and E. P. de Oliveira. 2019. Isoflavone supplementation plus combined aerobic and resistance exercise do not change phase angle values in postmenopausal women: A randomized placebo-controlled clinical trial. Experimental Gerontology 117:31–7. doi: 10.1016/j.exger.2018.08.007.
  • Barnes, S., J. Prasain, T. D'Alessandro, A. Arabshahi, N. Botting, M. Lila, G. Jackson, E. Janle, and C. Weaver. 2011. The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems. Food & Function 2 (5):235–44. doi: 10.1039/c1fo10025d.
  • Basu, P., and C. Maier. 2018. Phytoestrogens and breast cancer: In vitro anticancer activities of isoflavones, lignans, coumestans, stilbenes and their analogs and derivatives. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 107:1648–66. doi: 10.1016/j.biopha.2018.08.100.
  • Battistelli, M., and E. Falcieri. 2020. Apoptotic bodies: Particular extracellular vesicles involved in intercellular communication. Biology 9 (1):21. doi: 10.3390/biology9010021.
  • Bernatoniene, J., J. A. Kazlauskaite, and D. M. Kopustinskiene. 2021. Pleiotropic effects of isoflavones in inflammation and chronic degenerative diseases. International Journal of Molecular Sciences 22 (11):5656. doi: 10.3390/ijms22115656.
  • Bhatt, P. C., S. Pathak, V. Kumar, and B. P. Panda. 2018. Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer’s disease by fermented soybean nanonutraceutical. Inflammopharmacology 26 (1):105–18. doi: 10.1007/s10787-017-0381-9.
  • Bhatt, S., A. N. Nagappa, and C. R. Patil. 2020. Role of oxidative stress in depression. Drug Discovery Today 25 (7):1270–6. doi: 10.1016/j.drudis.2020.05.001.
  • Binda, A., C. Murano, and I. Rivolta. 2020. Innovative therapies and nanomedicine applications for the treatment of Alzheimer’s disease: A state-of-the-art (2017-2020). International Journal of Nanomedicine 15:6113–35. doi: 10.2147/IJN.S231480.
  • Bispo da Silva, A., P. L. Cerqueira Coelho, J. Alves Oliveira Amparo, M. M. Alves de Almeida Carneiro, J. M. Pereira Borges, C. dos Santos Souza, M. d F. Dias Costa, M. Mecha, C. Guaza Rodriguez, V. D. Amaral da Silva, et al. 2017. The flavonoid rutin modulates microglial/macrophage activation to a CD150/CD206 M2 phenotype. Chemico-Biological Interactions 274:89–99. doi: 10.1016/j.cbi.2017.07.004.
  • Blair, J. A., H. McGee, S. Bhatta, R. Palm, and G. Casadesus. 2015. Hypothalamic-pituitary-gonadal axis involvement in learning and memory and Alzheimer’s disease: More than "just" estrogen. Frontiers in Endocrinology 6:45– doi: 10.3389/fendo.2015.00045.
  • Blicharski, T., and A. Oniszczuk. 2017. Extraction methods for the isolation of isoflavonoids from plant material. Open Chemistry 15 (1):34–45. doi: 10.1515/chem-2017-0005.
  • Çalışkan, G., S. A. Raza, Y. E. Demiray, E. Kul, K. V. Sandhu, and O. Stork. 2021. Depletion of dietary phytoestrogens reduces hippocampal plasticity and contextual fear memory stability in adult male mouse. Nutritional Neuroscience 24 (12):951–62. doi: 10.1080/1028415X.2019.1698826.
  • Callahan, B. L., N. Ramakrishnan, P. Shammi, D. Bierstone, R. Taylor, M. Ozzoude, M. Goubran, D. T. Stuss, and S. E. Black. 2022. Cognitive and neuroimaging profiles of older adults with attention deficit/hyperactivity disorder presenting to a memory clinic. Journal of Attention Disorders 26 (8):1118–29. doi: 10.1177/10870547211060546.
  • Campbell, B. C. V., D. A. De Silva, M. R. Macleod, S. B. Coutts, L. H. Schwamm, S. M. Davis, and G. A. Donnan. 2019. Ischaemic stroke. Nature Reviews. Disease Primers 5 (1):70. doi: 10.1038/s41572-019-0118-8.
  • Canivenc-Lavier, M. C., and C. Bennetau-Pelissero. 2023. Phytoestrogens and health effects. Nutrients 15 (2):317. doi: 10.3390/nu15020317.
  • Capiluppi, E., L. Romano, P. Rebora, L. Nanetti, A. Castaldo, C. Gellera, C. Mariotti, A. Macerollo, and M. G. Cislaghi. 2020. Late-onset Huntington’s disease with 40-42 CAG expansion. Neurological Sciences 41 (4):869–76. doi: 10.1007/s10072-019-04177-8.
  • Castro, S. B. R., C. O. R. Junior, C. C. S. Alves, A. T. Dias, L. L. Alves, L. Mazzoccoli, F. P. Mesquita, N. S. V. Figueiredo, M. A. Juliano, M. C. M. N. Castañon, et al. 2012. Immunomodulatory effects and improved prognosis of experimental autoimmune encephalomyelitis after O-tetradecanoyl-genistein treatment. International Immunopharmacology 12 (2):465–70. doi: 10.1016/j.intimp.2011.12.025.
  • Cederroth, C. R., C. Zimmermann, and S. Nef. 2012. Soy, phytoestrogens and their impact on reproductive health. Molecular and Cell Endocrinology 355:192–200.
  • Chen, B. H., J. H. Park, J. H. Ahn, J. H. Cho, I. H. Kim, J. C. Lee, M. H. Won, C. H. Lee, I. K. Hwang, J. D. Kim, et al. 2017. Pretreated quercetin protects gerbil hippocampal CA1 pyramidal neurons from transient cerebral ischemic injury by increasing the expression of antioxidant enzymes. Neural Regenration Research 12:220–7.
  • Chen, D., C. Huang, and Z. Chen. 2019. A review for the pharmacological effect of lycopene in central nervous system disorders. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 111:791–801. doi: 10.1016/j.biopha.2018.12.151.
  • Chen, G., Y. Xu, H. Zhang, F. W. Muema, and M. Guo. 2023. Gymnema sylvestre extract ameliorated streptozotocin-induced hyperglycemia in T2DM rats via gut microbiota. Food Frontiers 4 (3):1426–39. doi: 10.1002/fft2.238.
  • Chen, G. F., T. H. Xu, Y. Yan, Y. R. Zhou, Y. Jiang, K. Melcher, and H. E. Xu. 2017. Amyloid beta: Structure, biology and structure-based therapeutic development. Acta Pharmacologica Sinica 38 (9):1205–35. doi: 10.1038/aps.2017.28.
  • Chen, H.-Q., X.-J. Wang, Z.-Y. Jin, X.-M. Xu, J.-W. Zhao, and Z.-J. Xie. 2008. Protective effect of isoflavones from Trifolium pratense on dopaminergic neurons. Neuroscience Research 62 (2):123–30. doi: 10.1016/j.neures.2008.07.001.
  • Chen, L., S. Ou, L. Zhou, H. Tang, J. Xu, and K. Guo. 2017. Formononetin attenuates Aβ25-35-induced cytotoxicity in HT22 cells via PI3K/Akt signaling and non-amyloidogenic cleavage of APP. Neuroscience Letters 639:36–42. doi: 10.1016/j.neulet.2016.12.064.
  • Chen, Q., W. Huang, E. Capanoglu, A. T. Amrouche, and B. Lu. 2023. Targeting mitochondrial quality control in muscle aging: Natural dietary products as potential interventions. Food Frontiers 4 (3):1206–41. doi: 10.1002/fft2.261.
  • Chen, T., C. Chen, Z. Zhang, Y. Zou, M. Peng, and Y. Wang. 2016. Toll-like receptor 4 knockout ameliorates neuroinflammation due to lung-brain interaction in mechanically ventilated mice. Brain Behavior and Immunity 56:42–55.
  • Cherry, J. D., Z. H. Baucom, K. G. Eppich, D. Kirsch, E. R. Dixon, Y. Tripodis, K. F. Bieniek, K. Farrell, K. Whitney, M. Uretsky, et al. 2022. Neuroimmune proteins can differentiate between tauopathies. Journal of Neuroinflammation 19 (1):278. doi: 10.1186/s12974-022-02640-6.
  • Choi, R. C. Y., J. T. T. Zhu, A. W. Y. Yung, P. S. C. Lee, S. L. Xu, A. J. Y. Guo, K. Y. Zhu, T. T. X. Dong, and K. W. K. Tsim. 2013. Synergistic action of flavonoids, baicalein, and daidzein in estrogenic and neuroprotective effects: A development of potential health products and therapeutic drugs against Alzheimer’s disease. Evidence-Based Complementary and Alternative Medicine. 2013:1–10.
  • Çiçek, S. S., M. Galarza Pérez, A. Wenzel-Storjohann, R. M. Bezerra, J. F. O. Segovia, U. Girreser, I. Kanzaki, and D. Tasdemir. 2022. Antimicrobial prenylated isoflavones from the leaves of the amazonian medicinal plant Vatairea guianensis Aubl. Journal of Natural Products 85 (4):927–35. doi: 10.1021/acs.jnatprod.1c01035.
  • Cichon, N., J. Saluk-Bijak, L. Gorniak, L. Przyslo, and M. Bijak. 2020. Flavonoids as a natural enhancer of neuroplasticity-an overview of the mechanism of neurorestorative action. Antioxidants 9 (11):1035. doi: 10.3390/antiox9111035.
  • Conforti, F., D. Rigano, F. Menichini, M. R. Loizzo, and F. Senatore. 2009. Protection against neurodegenerative diseases of Iris pseudopumila extracts and their constituents. Fitoterapia 80 (1):62–7. doi: 10.1016/j.fitote.2008.10.005.
  • Csaba, G. 2018. Effect of endocrine disruptor phytoestrogens on the immune system: Present and future. Acta Microbiologica et Immunologica Hungarica 65 (1):1–14. doi: 10.1556/030.65.2018.018.
  • Danciu, C., S. Avram, I. Z. Pavel, R. Ghiulai, C. A. Dehelean, A. Ersilia, D. Minda, C. Petrescu, E. A. Moaca, and C. Soica. 2018. Main isoflavones found in dietary sources as natural anti-inflammatory agents. Current Drug Targets 19 (7):841–53. doi: 10.2174/1389450118666171109150731.
  • de Rus Jacquet, A., A. Ambaw, M. A. Tambe, S. Y. Ma, M. Timmers, M. H. Grace, Q. L. Wu, J. E. Simon, G. P. McCabe, M. A. Lila, et al. 2021. Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson’s disease models. Food & Function 12 (23):11987–2007. doi: 10.1039/d1fo00007a.
  • De Vos, K. J., and M. Hafezparast. 2017. Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research? Neurobiology of Disease 105:283–99. doi: 10.1016/j.nbd.2017.02.004.
  • Del Rio, D., A. Rodriguez-Mateos, J. P. E. Spencer, M. Tognolini, G. Borges, and A. Crozier. 2013. Dietary (poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxidants & Redox Signaling 18 (14):1818–92. doi: 10.1089/ars.2012.4581.
  • Devi, S., V. Kumar, S. K. Singh, A. K. Dubey, and J. J. Kim. 2021. Flavonoids: Potential candidates for the treatment of neurodegenerative disorders. Biomedicines 9 (2):99. doi: 10.3390/biomedicines9020099.
  • Dias, A. T., S. B. R. de Castro, C. C. de Souza Alves, M. G. Evangelista, L. C. da Silva, D. R. d L. Reis, M. A. Machado, M. A. Juliano, and A. P. Ferreira. 2018. Genistein modulates the expression of Toll-like receptors in experimental autoimmune encephalomyelitis. Inflammation Research 67 (7):597–608. doi: 10.1007/s00011-018-1146-7.
  • Ding, B., L. Yuan, H. Yu, L. Li, W. Ma, Y. Bi, J. Feng, and R. Xiao. 2011. Genistein and folic acid prevent oxidative injury induced by β-amyloid peptide. Basic & Clinical Pharmacology & Toxicology 108 (5):333–40. doi: 10.1111/j.1742-7843.2010.00661.x.
  • Ding, C., Y. Wu, X. Chen, Y. Chen, Z. Wu, Z. Lin, D. Kang, W. Fang, and F. Chen. 2022. Global, regional, and national burden and attributable risk factors of neurological disorders: The Global Burden of Disease study 1990-2019. Frontiers in Public Health 10:952161. doi: 10.3389/fpubh.2022.952161.
  • Domańska, A., A. Orzechowski, A. Litwiniuk, M. Kalisz, W. Bik, and A. Baranowska-Bik. 2021. The beneficial role of natural endocrine disruptors: Phytoestrogens in Alzheimer’s disease. Oxidative Medicine and Cellular Longevity 2021:3961445–17. doi: 10.1155/2021/3961445.
  • Domenighetti, C., V. Douillard, P. E. Sugier, A. A. K. Sreelatha, C. Schulte, S. Grover, P. May, D. R. Bobbili, M. Radivojkov-Blagojevic, P. Lichtner, et al. 2022. The interaction between HLA-DRB1 and smoking in Parkinson’s disease revisited. Movement Disorders 37 (9):1929–37. doi: 10.1002/mds.29133.
  • Domínguez-López, I., M. Yago-Aragón, A. Salas-Huetos, A. Tresserra-Rimbau, and S. Hurtado-Barroso. 2020. Effects of dietary phytoestrogens on hormones throughout a human lifespan: A review. Nutrients 12 (8):2456. doi: 10.3390/nu12082456.
  • Dominiak, K., J. McKinney, L. K. Heilbrun, and F. H. Sarkar. 2010. Critical need for clinical trials: An example of a pilot human intervention trial of a mixture of natural agents protecting lymphocytes against TNF-alpha induced activation of NF-kappaB. Pharmaceutical Research 27 (6):1061–5. doi: 10.1007/s11095-010-0113-y.
  • Dong, N., and Z. Yang. 2022. Glycitein exerts neuroprotective effects in Rotenone-triggered oxidative stress and apoptotic cell death in the cellular model of Parkinson’s disease. Acta Biochimica Polonica 69 (2):447–52. doi: 10.18388/abp.2020_5963.
  • Dos Santos, T. C., T. M. Gomes, B. A. S. Pinto, A. L. Camara, and A. M. A. Paes. 2018. Naturally occurring acetylcholinesterase inhibitors and their potential use for Alzheimer’s disease therapy. Frontiers in Pharmacology 9:1192. doi: 10.3389/fphar.2018.01192.
  • Du, Z. R., X. Q. Feng, N. Li, J. X. Qu, L. Feng, L. Chen, and W. F. Chen. 2018. G protein-coupled estrogen receptor is involved in the anti-inflammatory effects of genistein in microglia. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 43:11–20. doi: 10.1016/j.phymed.2018.03.039.
  • Duan, X., Y. Li, F. Xu, and H. Ding. 2021. Study on the neuroprotective effects of Genistein on Alzheimer’s disease. Brain and Behavior 11 (5): E02100. doi: 10.1002/brb3.2100.
  • Duru, K. C., E. G. Kovaleva, I. G. Danilova, P. van der Bijl, and A. V. Belousova. 2018. The potential beneficial role of isoflavones in type 2 diabetes mellitus. Nutrition Research 59:1–15. doi: 10.1016/j.nutres.2018.06.005.
  • Edison, P. 2020. Neuroinflammation, microglial activation, and glucose metabolism in neurodegenerative diseases. International Review of Neurobiology 154:325–44. doi: 10.1016/bs.irn.2020.03.017.
  • El-Sherbeeny, N. A., N. Soliman, A. M. Youssef, N. M. Abd El-Fadeal, T. B. El-Abaseri, A. A. Hashish, W. K. Abdelbasset, G. El-Saber Batiha, and S. A. Zaitone. 2020. The protective effect of biochanin A against rotenone-induced neurotoxicity in mice involves enhancing of PI3K/Akt/mTOR signaling and beclin-1 production. Ecotoxicology and Environmental Safety 205:111344. doi: 10.1016/j.ecoenv.2020.111344.
  • Engel, D. F., and L. A. Velloso. 2022. The timeline of neuronal and glial alterations in experimental obesity. Neuropharmacology 208:108983. doi: 10.1016/j.neuropharm.2022.108983.
  • Fei, H. X., Y. B. Zhang, T. Liu, X. J. Zhang, and S. L. Wu. 2018. Neuroprotective effect of formononetin in ameliorating learning and memory impairment in mouse model of Alzheimer’s disease. Bioscience, Biotechnology, and Biochemistry 82 (1):57–64. doi: 10.1080/09168451.2017.1399788.
  • Fields, C. R., N. Bengoa-Vergniory, and R. Wade-Martins. 2019. Targeting alpha-synuclein as a therapy for Parkinson’s disease. Frontiers in Molecular Neuroscience 12:299. doi: 10.3389/fnmol.2019.00299.
  • Fouda, A. Y., B. Pillai, K. M. Dhandapani, A. Ergul, and S. C. Fagan. 2017. Role of interleukin-10 in the neuroprotective effect of the Angiotensin Type 2 receptor agonist, compound 21, after ischemia/reperfusion injury. European Journal of Pharmacology 799:128–34. doi: 10.1016/j.ejphar.2017.02.016.
  • Fujii, S., N. Takahashi, H. Inoue, S. Katsumata, Y. Kikkawa, M. Machida, Y. Ishimi, and M. Uehara. 2016. A combination of soy isoflavones and cello-oligosaccharides changes equol/O-desmethylangolensin production ratio and attenuates bone fragility in ovariectomized mice. Bioscience, Biotechnology, and Biochemistry 80 (8):1632–5. doi: 10.1080/09168451.2016.1184559.
  • Fuloria, S., M. A. A. Yusri, M. Sekar, S. H. Gan, N. Rani, P. T. Lum, S. Ravi, V. Subramaniyan, A. K. Azad, S. Jeyabalan, et al. 2022. Genistein: A potential natural lead molecule for new drug design and development for treating memory impairment. Molecules 27 (1):265. doi: 10.3390/molecules27010265.
  • Fung, T. C., C. A. Olson, and E. Y. Hsiao. 2017. Interactions between the microbiota, immune and nervous systems in health and disease. Nature Neuroscience 20 (2):145–55. doi: 10.1038/nn.4476.
  • Gaeta, A., and R. C. Hider. 2005. The crucial role of metal ions in neurodegeneration: The basis for a promising therapeutic strategy. British Journal of Pharmacology 146 (8):1041–59. doi: 10.1038/sj.bjp.0706416.
  • Ganesan, K., S. Mickymaray, M. S. Al Aboody, F. A. Alfaiz, R. Thatchinamoorthi, and B. Xu. 2020. Immunomodulatory and antineoplastic efficacy of common spices and their connection with phenolic antioxidants. Bioactive Compounds in Health and Disease 3 (2):15–31. doi: 10.31989/bchd.v3i2.687.
  • Ganesan, K., J. L. Quiles, M. Daglia, J. Xiao, and B. Xu. 2021. Dietary phytochemicals modulate intestinal epithelial barrier dysfunction and autoimmune diseases. Food Frontiers 2 (3):357–82. doi: 10.1002/fft2.102.
  • Ganesan, K., K. M. Ramkumar, and B. Xu. 2020. Vitexin restores pancreatic β-cell function and insulin signaling through Nrf2 and NF-κB signaling pathways. European Journal of Pharmacology 888:173606. doi: 10.1016/j.ejphar.2020.173606.
  • Ganesan, K., K. Sukalingam, and B. Xu. 2017. Solanum trilobatum L. ameliorate thioacetamide-induced oxidative stress and hepatic damage in albino rats. Antioxidants 6 (3):68. doi: 10.3390/antiox6030068.
  • Ganesan, K., and B. Xu. 2017a. A critical review on polyphenols and health benefits of black soybeans. Nutrients 9 (5):455. doi: 10.3390/nu9050455.
  • Ganesan, K., and B. Xu. 2017b. Polyphenol-rich dry common beans (Phaseolus vulgaris L.) and their health benefits. International Journal of Molecular Sciences 18 (11):2331. doi: 10.3390/ijms18112331.
  • Ganesan, K., and B. Xu. 2017c. Polyphenol-rich lentils and their health promoting effects. International Journal of Molecular Sciences 18:2390.
  • Ganesan, K., and B. Xu. 2018. Anti-obesity effects of medicinal and edible mushrooms. Molecules 23 (11):2880. doi: 10.3390/molecules23112880.
  • Ganesan, K., and B. Xu. 2019. Anti-diabetic effects and mechanisms of dietary polysaccharides. Molecules 24 (14):2556. doi: 10.3390/molecules24142556.
  • Gao, Y., Z. Zong, W. Xia, X. Fang, R. Liu, W. Wu, H. Mu, Y. Han, S. Xiao, H. Gao, et al. 2023. Hepatoprotective effect of water bamboo shoot (Zizania latifolia) extracts against acute alcoholic liver injury in a mice model and screening of bioactive phytochemicals. Food Frontiers 4 (3):1362–71. doi: 10.1002/fft2.217.
  • Garg, S., V. K. Lule, R. K. Malik, and S. K. Tomar. 2016. Soy bioactive components in functional perspective: A review. International Journal of Food Properties 19 (11):2550–74. doi: 10.1080/10942912.2015.1136936.
  • Gendy, A. M., A. Soubh, M. R. Elnagar, E. Hamza, K. A. Ahmed, A. Aglan, A. E. El-Haddad, M. A. Farag, and H. M. El-Sadek. 2023. New insights into the role of berberine against 3-nitropropionic acid-induced striatal neurotoxicity: Possible role of BDNF-TrkB-PI3K/Akt and NF-κB signaling. Food and Chemical Toxicology 175:113721. doi: 10.1016/j.fct.2023.113721.
  • Geng, L. M., and J. G. Jiang. 2022. The neuroprotective effects of formononetin: Signaling pathways and molecular targets. Journal of Functional Foods 88:104911. doi: 10.1016/j.jff.2021.104911.
  • Glaser, T., V. F. Arnaud Sampaio, C. Lameu, and H. Ulrich. 2019. Calcium signalling: A common target in neurological disorders and neurogenesis. Seminar in Cell & Developmental Biology 95:25–33.
  • Glisic, M., N. Kastrati, J. Musa, J. Milic, E. Asllanaj, E. Portilla Fernandez, J. Nano, C. Ochoa Rosales, M. Amiri, B. Kraja, et al. 2018. Phytoestrogen supplementation and body composition in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials. Maturitas 115:74–83. doi: 10.1016/j.maturitas.2018.06.012.
  • Goel, R., and R. Chaudhary. 2020. Effect of daidzein on Parkinson disease induced by reserpine in rats. Brazilian Journal of Pharmaceutical Sciences 56:e18388. doi: 10.1590/s2175-97902019000318388.
  • Gómez-Zorita, S., M. González-Arceo, A. Fernández-Quintela, I. Eseberri, J. Trepiana, and M. P. Portillo. 2020. Scientific evidence supporting the beneficial effects of isoflavones on human health. Nutrients 12 (12):3853. doi: 10.3390/nu12123853.
  • Gonda, X., P. Dome, J. C. Neill, and F. I. Tarazi. 2023. Novel antidepressant drugs: Beyond monoamine targets. CNS Spectrums 28 (1):6–15. doi: 10.1017/S1092852921000791.
  • Gong, G., K. Ganesan, Q. Xiong, and Y. Zheng. 2023. Anti-invasive and anti-migratory effects of ononin on human osteosarcoma cells by limiting the MMP2/9 and EGFR-Erk1/2 pathway. Cancers 15 (3):758. doi: 10.3390/cancers15030758.
  • Gonzalez, J., J. C. Jurado-Coronel, M. F. Ávila, A. Sabogal, F. Capani, and G. E. Barreto. 2015. NMDARs in neurological diseases: A potential therapeutic target. The International Journal of Neuroscience 125 (5):315–27. doi: 10.3109/00207454.2014.940941.
  • Goodin, S., F. Shen, W. J. Shih, N. Dave, M. P. Kane, P. Medina, G. H. Lambert, J. Aisner, M. Gallo, and R. S. DiPaola. 2007. Clinical and biological activity of soy protein powder supplementation in healthy male volunteers. Cancer Epidemiology, Biomarkers & Prevention 16 (4):829–33. doi: 10.1158/1055-9965.EPI-06-0882.
  • Gorzkiewicz, J., G. Bartosz, and I. Sadowska-Bartosz. 2021. The potential effects of phytoestrogens: The role in neuroprotection. Molecules 26 (10):2954. doi: 10.3390/molecules26102954.
  • Gouda, N. A., A. Elkamhawy, and J. Cho. 2022. Emerging therapeutic strategies for Parkinson’s disease and future prospects: A 2021 update. Biomedicines 10 (2):371. doi: 10.3390/biomedicines10020371.
  • Gu, Y., J. Chen, and J. Shen. 2014. Herbal medicines for ischemic stroke: Combating inflammation as therapeutic targets. Journal of Neuroimmune Pharmacology 9 (3):313–39. doi: 10.1007/s11481-014-9525-5.
  • Guo, C., L. Sun, X. Chen, and D. Zhang. 2013. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Research 8:2003–14.
  • Guo, L. Y., B. Lozinski, and V. W. Yong. 2019. Exercise in multiple sclerosis and its models: Focus on the central nervous system outcomes. Journal of Neuroscience Research 98 (3):509–23. doi: 10.1002/jnr.24524.
  • Gupta, A., A. K. Singh, R. Kumar, S. Jamieson, A. K. Pandey, and A. Bishayee. 2021. Neuroprotective potential of ellagic acid: A critical review. Advances in Nutrition 12 (4):1211–38. doi: 10.1093/advances/nmab007.
  • Gutierrez-Zepeda, A., R. Santell, Z. Wu, M. Brown, Y. Wu, I. Khan, C. D. Link, B. Zhao, and Y. Luo. 2005. Soy isoflavone glycitein protects against beta amyloid-induced toxicity and oxidative stress in transgenic Caenorhabditis elegans. BMC Neuroscience 6 (1):54. doi: 10.1186/1471-2202-6-54.
  • Hamnett, R., L. B. Dershowitz, V. Sampathkumar, Z. Wang, J. Gomez-Frittelli, V. De Andrade, N. Kasthuri, S. Druckmann, and J. A. Kaltschmidt. 2022. Regional cytoarchitecture of the adult and developing mouse enteric nervous system. Current Biology 32 (20):4483–92.e5. doi: 10.1016/j.cub.2022.08.030.
  • Hardiman, O., A. Al-Chalabi, A. Chio, E. M. Corr, G. Logroscino, W. Robberecht, P. J. Shaw, Z. Simmons, and L. H. van den Berg. 2017. Amyotrophic lateral sclerosis. Nature Reviews. Disease Primers 3 (1):17071. doi: 10.1038/nrdp.2017.71.
  • Haron, S., E. J. Kilmister, P. F. Davis, S. S. Stylli, T. Mantamadiotis, A. H. Kaye, S. R. Hall, S. T. Tan, and A. C. Wickremesekera. 2021. The renin-angiotensin system in central nervous system tumors and degenerative diseases. Frontiers in Bioscience 26:628–42.
  • Hofmann, P. J., L. Schomburg, and J. Köhrle. 2009. Interference of endocrine disrupters with thyroid hormone receptor-dependent transactivation. Toxicological Sciences 110 (1):125–37. doi: 10.1093/toxsci/kfp086.
  • Hong, H., X. Lu, Q. Lu, C. Huang, and Z. Cui. 2022. Potential therapeutic effects and pharmacological evidence of sinomenine in central nervous system disorders. Frontiers in Pharmacology 13:1015035. doi: 10.3389/fphar.2022.1015035.
  • Hosoda, K., T. Furuta, A. Yokokawa, and K. Ishii. 2010. Identification and quantification of daidzein-7-glucuronide-4′-sulfate, genistein-7-glucuronide-4′-sulfate and genistein-4′,7-diglucuronide as major metabolites in human plasma after administration of kinako. Analytical and Bioanalytical Chemistry 397 (4):1563–72. doi: 10.1007/s00216-010-3714-8.
  • Hou, Y., W. Zhao, H. Yu, F. Zhang, H. T. Zhang, and Y. Zhou. 2022. Biochanin A alleviates cognitive impairment and hippocampal mitochondrial damage in ovariectomized APP/PS1 mice. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 100:154056. doi: 10.1016/j.phymed.2022.154056.
  • Huang, B., X. Wang, Q. Li, and T. Wang. 2017. Formononetin reduces inflammation in focal brain ischemia reperfusion ratvia inhibiting sphingosine kinase 1/sphingosine 1-phosphate signaling pathway. Acta Universitatis Medicinalis Nanjing 10:1239–42.
  • Huang, Q., X. Xiao, J. Yu, Y. Yang, J. Yu, Y. Liu, H. Song, T. Han, D. Zhang, X. Niu, et al. 2022. Tectoridin exhibits anti-rheumatoid arthritis activity through the inhibition of the inflammatory response and the MAPK pathway in vivo and in vitro. Archives of Biochemistry and Biophysics 727:109328. doi: 10.1016/j.abb.2022.109328.
  • Hwang, W. J., T. Y. Lee, N. S. Kim, and J. S. Kwon. 2020. The role of estrogen receptors and their signaling across psychiatric disorders. International Journal of Molecular Sciences 22 (1):373. doi: 10.3390/ijms22010373.
  • Islam, T., K. Ganesan, and B. Xu. 2019. New insight into mycochemical profiles and antioxidant potential of edible and medicinal mushrooms: A review. Internatonal Journal of Medicinal Mushrooms 21:237–51.
  • Islam, T., K. Ganesan, and B. Xu. 2021. Insights into health-promoting effects of Jew’s ear (Auricularia auricula-judae). Trends in Food Science & Technology 114:552–69. doi: 10.1016/j.tifs.2021.06.017.
  • Ito, S., H. Sasaki, T. Gotow, I. Suetake, and K. Nagai. 2023. Soy isoflavone daidzein protects Neuro2a cells from NO stress via activation of AMPK-PGC1α pathway followed by mitochondrial enhancement. PharmaNutrition 24:100337. doi: 10.1016/j.phanu.2023.100337.
  • Izzo, A. A., S. Hoon-Kim, R. Radhakrishnan, and E. M. Williamson. 2016. A critical approach to evaluating clinical efficacy, adverse events and drug interactions of herbal remedies. Phytotherapy Research 30 (5):691–700. doi: 10.1002/ptr.5591.
  • Jahromi, S. R., M. Togha, A. Ghaemi, A. Alizadeh, R. Doosti, and H. M. Tabriz. 2015. ISDN2014_0367: Alleviation of experimental allergic encephalomyelitis in C57BL/6 mice by soy daidzein. International Journal of Developmental Neuroscience 47 (Part_A):108– doi: 10.1016/j.ijdevneu.2015.04.295.
  • Jayasuriya, R., K. Ganesan, B. Xu, and K. M. Ramkumar. 2022. Emerging role of long non-coding RNAs in endothelial dysfunction and their molecular mechanisms. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 145:112421. doi: 10.1016/j.biopha.2021.112421.
  • Jensen, S. N., N. M. Cady, S. K. Shahi, S. R. Peterson, A. Gupta, K. N. Gibson-Corley, and A. K. Mangalam. 2021. Isoflavone diet ameliorates experimental autoimmune encephalomyelitis through modulation of gut bacteria depleted in patients with multiple sclerosis. Science Advances 7 (28):eabd4595. doi: 10.1126/sciadv.abd4595.
  • Jhamandas, J. H., C. Cho, B. Jassar, K. Harris, D. MacTavish, and J. Easaw. 2001. Cellular mechanisms for amyloid β-protein activation of rat cholinergic basal forebrain neurons. Journal of Neurophysiology 86 (3):1312–20. doi: 10.1152/jn.2001.86.3.1312.
  • Jin, W. N., R. Gonzales, Y. Feng, K. Wood, Z. Chai, J. F. Dong, A. La Cava, F. D. Shi, and Q. Liu. 2018. Brain ischemia induces diversified neuroantigen-specific T-cell responses that exacerbate brain injury. Stroke 49 (6):1471–8. doi: 10.1161/STROKEAHA.118.020203.
  • Jurcau, A. 2021. Insights into the pathogenesis of neurodegenerative diseases: Focus on mitochondrial dysfunction and oxidative stress. International Journal of Molecular Sciences 22 (21):11847. doi: 10.3390/ijms222111847.
  • Kajta, M., H. Domin, G. Grynkiewicz, and W. Lason. 2007. Genistein inhibits glutamate-induced apoptotic processes in primary neuronal cell cultures: An involvement of aryl hydrocarbon receptor and estrogen receptor/glycogen synthase kinase-3β intracellular signaling pathway. Neuroscience 145 (2):592–604. doi: 10.1016/j.neuroscience.2006.11.059.
  • Kamel, H., and C. Iadecola. 2012. Brain-immune interactions and ischemic stroke: Clinical implications. Archives of Neurology 69 (5):576–81. doi: 10.1001/archneurol.2011.3590.
  • Kametani, F., and M. Hasegawa. 2018. Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer’s disease. Frontiers in Neuroscience 12:25– doi: 10.3389/fnins.2018.00025.
  • Katsumoto, A., H. Takeuchi, and F. Tanaka. 2019. Tau pathology in chronic traumatic encephalopathy and Alzheimer’s disease: Similarities and differences. Frontiers in Neurology 10:980. doi: 10.3389/fneur.2019.00980.
  • Kausar, S., F. Wang, and H. Cui. 2018. The role of mitochondria in reactive oxygen species generation and its implications for neurodegenerative diseases. Cells 7 (12):274. doi: 10.3390/cells7120274.
  • Ke, T., A. Santamaria, F. Barbosa, Jr., J. B. T. Rocha, A. V. Skalny, A. A. Tinkov, A. B. Bowman, and M. Aschner. 2022. Developmental methylmercury exposure induced and age-dependent glutamatergic neurotoxicity in Caenorhabditis elegans. Neurochemical Research 48 (3):920–8. doi: 10.1007/s11064-022-03816-5.
  • Kent, S. A., T. L. Spires-Jones, and C. S. Durrant. 2020. The physiological roles of tau and Aβ: Implications for Alzheimer’s disease pathology and therapeutics. Acta Neuropathologica 140 (4):417–47. doi: 10.1007/s00401-020-02196-w.
  • Khanna, S., R. Stewart, S. Gnyawali, H. Harris, M. Balch, J. Spieldenner, C. K. Sen, and C. Rink. 2017. Phytoestrogen isoflavone intervention to engage the neuroprotective effect of glutamate oxaloacetate transaminase against stroke. FASEB Journal 31 (10):4533–44. doi: 10.1096/fj.201700353.
  • Kim, E., M. S. Woo, L. Qin, T. Ma, C. D. Beltran, Y. Bao, J. A. Bailey, D. Corbett, R. R. Ratan, D. K. Lahiri, et al. 2015. Daidzein augments cholesterol homeostasis via ApoE to promote functional recovery in chronic stroke. The Journal of Neuroscience 35 (45):15113–26. doi: 10.1523/JNEUROSCI.2890-15.2015.
  • Kim, I. S. 2021. Current perspectives on the beneficial effects of soybean isoflavones and their metabolites for humans. Antioxidants 10 (7):1064. doi: 10.3390/antiox10071064.
  • Kim, S. K., Y. H. Ko, Y. Lee, S. Y. Lee, and C. G. Jang. 2021. Antineuroinflammatory effects of 7,3',4'-trihydroxyisoflavone in lipopolysaccharide-stimulated BV2 microglial cells through MAPK and NF-κB signaling suppression. Biomolecules & Therapeutics 29 (2):127–34. doi: 10.4062/biomolther.2020.093.
  • Kim, T., H. S. Kim, J. Jang, D. J. Kim, J. Lee, D. Lee, and S. H. Kim. 2022. Synthesis of 7,2'-dihydroxy-4',5'-dimethoxyisoflavanone, a phytoestrogen with derma papilla cell proliferative activity. Molecules 27 (19):6660. doi: 10.3390/molecules27196660.
  • Ko, K. P. 2014. Isoflavones: Chemistry, analysis, functions and effects on health and cancer. Asian Pacific Journal of Cancer Prevention 15 (17):7001–10. doi: 10.7314/apjcp.2014.15.17.7001.
  • Ko, Y. H., S. H. Kwon, S. K. Kim, B. R. Lee, K. H. Hur, Y. J. Kim, S. E. Kim, S. Y. Lee, and C. G. Jang. 2019. Protective effects of 6,7,4'-trihydroxyisoflavone, a major metabolite of daidzein, on 6-hydroxydopamine-induced neuronal cell death in SH-SY5Y human neuroblastoma cells. Archives of Pharmacal Research 42 (12):1081–91. doi: 10.1007/s12272-019-01191-4.
  • Kostelac, D., G. Rechkemmer, and K. Briviba. 2003. Phytoestrogens modulate binding response of estrogen receptors alpha and beta to the estrogen response element. Journal of Agricultural and Food Chemistry 51 (26):7632–5. doi: 10.1021/jf034427b.
  • Kövesdi, E., E. Szabó-Meleg, and I. M. Abrahám. 2020. The role of estradiol in traumatic brain injury: Mechanism and treatment potential. International Journal of Molecular Sciences 22 (1):11. doi: 10.3390/ijms22010011.
  • Kulkarni, J., S. Butler, and A. Riecher-Rössler. 2019. Estrogens and SERMS as adjunctive treatments for schizophrenia. Frontiers in Neuroendocrinology 53:100743. doi: 10.1016/j.yfrne.2019.03.002.
  • Kuryłowicz, A. 2020. The role of isoflavones in type 2 diabetes prevention and treatment-A narrative review. International Journal of Molecular Science 22:218.
  • Ladak, A. A., S. A. Enam, and M. T. Ibrahim. 2019. A review of the molecular mechanisms of traumatic brain injury. World Neurosurgery 131:126–32. doi: 10.1016/j.wneu.2019.07.039.
  • Lamptey, R. N. L., C. Sun, B. Layek, and J. Singh. 2023. Neurogenic hypertension, the blood-brain barrier, and the potential role of targeted nanotherapeutics. International Journal of Molecular Science 24:2213.
  • Li, J., Z. Jiang, X. Li, Y. Hou, F. Liu, N. Li, X. Liu, L. Yang, and G. Chen. 2015. Natural therapeutic agents for neurodegenerative diseases from a traditional herbal medicine Pongamia pinnata (L.) Pierre. Bioorganic & Medicinal Chemistry Letters 25 (1):53–8. doi: 10.1016/j.bmcl.2014.11.015.
  • Li, J., H. Xiang, C. Huang, and J. Lu. 2021. Pharmacological actions of myricetin in the nervous system: A comprehensive review of preclinical studies in animals and cell models. Frontiers in Pharmacology 12:797298. doi: 10.3389/fphar.2021.797298.
  • Li, R.-Z., X.-W. Ding, T. Geetha, L. Al-Nakkash, T. L. Broderick, and J. R. Babu. 2020. Beneficial effect of genistein on diabetes-induced brain damage in the ob/ob mouse model. Drug Design, Development and Therapy 14:3325–36. doi: 10.2147/DDDT.S249608.
  • Li, Y., Y. Liu, Y. Xu, H. Chen, Z. Yan, and X. Wang. 2019. Aggravated behavioral and neurochemical deficits and redox imbalance in mice with enhanced neonatal iron intake: Improvement by biochanin A and role of microglial p38 activation. Nutritional Neuroscience 24 (3):161–72. doi: 10.1080/1028415X.2019.1611021.
  • Li, Y., J. J. Zhang, R. J. Chen, L. Chen, S. Chen, X. F. Yang, and J. W. Min. 2022. Genistein mitigates oxidative stress and inflammation by regulating Nrf2/HO-1 and NF-κB signaling pathways in hypoxic-ischemic brain damage in neonatal mice. Annals of Translational Medicine 10 (2):32– doi: 10.21037/atm-21-4958.
  • Li, Z., G. Zeng, X. Zheng, W. Wang, Y. Ling, H. Tang, and J. Zhang. 2018. Neuroprotective effect of formononetin against TBI in rats via suppressing inflammatory reaction in cortical neurons. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 106:349–54. doi: 10.1016/j.biopha.2018.06.041.
  • Liang, C., S. Tan, Q. Huang, J. Lin, Z. Lu, and X. Lin. 2015. Pratensein ameliorates β-amyloid-induced cognitive impairment in rats via reducing oxidative damage and restoring synapse and BDNF levels. Neuroscience Letters 592:48–53. doi: 10.1016/j.neulet.2015.03.003.
  • Liang, F., and S. Xie. 2017. Puerarin prevents tumor necrosis factor-α-induced apoptosis of PC12 cells via activation of the PI3K/Akt signaling pathway. Experimental and Therapeutic Medicine 14 (1):813–8. doi: 10.3892/etm.2017.4545.
  • Liang, K., Y. Ye, Y. Wang, J. Zhang, and C. Li. 2014. Formononetin mediates neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway. Journal of the Neurological Sciences 344 (1-2):100–4. doi: 10.1016/j.jns.2014.06.033.
  • Liao, W., G. Jin, M. Zhao, and H. Yang. 2013. The effect of genistein on the content and activity of α- and β-secretase and protein kinase C in Aβ-injured hippocampal neurons. Basic & Clinical Pharmacology & Toxicology 112 (3):182–5. doi: 10.1111/bcpt.12009.
  • Lim, H. S., Y. J. Kim, B. Y. Kim, G. Park, and S. J. Jeong. 2018. The anti-neuroinflammatory activity of tectorigenin pretreatment via downregulated NF-κB and ERK/JNK pathways in BV-2 microglial and microglia inactivation in mice with lipopolysaccharide. Frontiers in Pharmacology 9:462. doi: 10.3389/fphar.2018.00462.
  • Lin, L. G., Q. Y. Liu, and Y. Ye. 2014. Naturally occurring homoisoflavonoids and their pharmacological activities. Planta Medica 80 (13):1053–66. doi: 10.1055/s-0034-1383026.
  • Liu, L. X., W. F. Chen, J. X. Xie, and M. S. Wong. 2008. Neuroprotective effects of genistein on dopaminergic neurons in the mice model of Parkinson’s disease. Neuroscience Research 60 (2):156–61. doi: 10.1016/j.neures.2007.10.005.
  • Long-Smith, C., K. J. O'Riordan, G. Clarke, C. Stanton, T. G. Dinan, and J. F. Cryan. 2020. Microbiota-gut-brain axis: New therapeutic opportunities. Annual Review of Pharmacology and Toxicology 60 (1):477–502. doi: 10.1146/annurev-pharmtox-010919-023628.
  • Lossi, L. 2022. The concept of intrinsic versus extrinsic apoptosis. The Biochemical Journal 479 (3):357–84. doi: 10.1042/BCJ20210854.
  • Lu, C., Y. Wang, T. Xu, Q. Li, D. Wang, L. Zhang, B. Fan, F. Wang, and X. Liu. 2018. Genistein ameliorates scopolamine-induced amnesia in mice through the regulation of the cholinergic neurotransmission, antioxidant system and the ERK/CREB/BDNF signaling. Frontiers in Pharmacology 9:1153– doi: 10.3389/fphar.2018.01153.
  • Ma, W. W., C. C. Hou, X. Zhou, H. l Yu, Y. D. Xi, J. Ding, X. Zhao, and R. Xiao. 2013. Genistein alleviates the mitochondria-targeted DNA damage induced by β-amyloid peptides 25-35 in C6 glioma cells. Neurochemical Research 38 (7):1315–23. doi: 10.1007/s11064-013-1019-y.
  • Ma, X., A. Aravind, B. J. Pfister, N. Chandra, and J. Haorah. 2019. Animal models of traumatic brain injury and assessment of injury severity. Molecular Neurobiology 56 (8):5332–45. doi: 10.1007/s12035-018-1454-5.
  • Ma, X., and J. Wang. 2022. Formononetin: A pathway to protect neurons. Frontiers in Integrative Neuroscience 16:908378. doi: 10.3389/fnint.2022.908378.
  • Ma, Y., J. C. Sullivan, and D. A. Schreihofer. 2010. Dietary genistein and equol (4′, 7 isoflavandiol) reduce oxidative stress and protect rats against focal cerebral ischemia. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 299 (3):R871–R877. doi: 10.1152/ajpregu.00031.2010.
  • Mannan, A., T. G. Singh, V. Singh, N. Garg, A. Kaur, and M. Singh. 2022. Insights into the mechanism of the therapeutic potential of herbal monoamine oxidase inhibitors in neurological diseases. Current Drug Targets 23 (3):286–310. doi: 10.2174/1389450122666210707120256.
  • Margeat, E., A. Bourdoncle, R. Margueron, N. Poujol, V. Cavaillès, and C. Royer. 2003. Ligands differentially modulate the protein interactions of the human estrogen receptors alpha and beta. Journal of Molecular Biology 326 (1):77–92. doi: 10.1016/s0022-2836(02)01355-4.
  • Marini, H. R. 2022. Mediterranean diet and soy isoflavones for integrated management of the menopausal metabolic syndrome. Nutrients 14 (8):1550. doi: 10.3390/nu14081550.
  • Martinez, J. E., D. D. Kahana, S. Ghuman, H. P. Wilson, J. Wilson, S. C. J. Kim, V. Lagishetty, J. P. Jacobs, A. P. Sinha-Hikim, and T. C. Friedman. 2021. Unhealthy lifestyle and gut dysbiosis: A better understanding of the effects of poor diet and nicotine on the intestinal microbiome. Frontiers in Endocrinology 12:667066. doi: 10.3389/fendo.2021.667066.
  • May, F. E. 2014. Novel drugs that target the estrogen-related receptor alpha: Their therapeutic potential in breast cancer. Cancer Management and Research 6:225–52. doi: 10.2147/CMAR.S35024.
  • Mayne, K., J. A. White, C. E. McMurran, F. J. Rivera, and A. G. de la Fuente. 2020. Aging and neurodegenerative disease: Is the adaptive immune system a friend or foe? Frontiers in Aging Neuroscience 12:572090. doi: 10.3389/fnagi.2020.572090.
  • McEwen, B. S., and T. A. Milner. 2007. Hippocampal formation: Shedding light on the influence of sex and stress on the brain. Brain Research Reviews 55 (2):343–55. doi: 10.1016/j.brainresrev.2007.02.006.
  • Megha, K. B., X. Joseph, V. Akhil, and P. V. Mohanan. 2021. Cascade of immune mechanism and consequences of inflammatory disorders. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 91:153712. doi: 10.1016/j.phymed.2021.153712.
  • Menze, E. T., A. Esmat, M. G. Tadros, A. B. Abdel-Naim, and A. E. Khalifa. 2015. Genistein improves 3-NPA-induced memory impairment in ovariectomized rats: Impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties. PloS One 10 (2):e0117223. doi: 10.1371/journal.pone.0117223.
  • Menze, E. T., A. Esmat, M. G. Tadros, A. E. Khalifa, and A. B. Abdel-Naim. 2016. Genistein improves sensorimotor gating: Mechanisms related to its neuroprotective effects on the striatum. Neuropharmacology 252:109964–46. doi: 10.1016/j.neuropharm.2024.109964.
  • Messina, M., J. Hamilton-Reeves, M. Kurzer, and W. Phipps. 2007. Effect of soy protein on testosterone levels. Cancer Epidemiology, Biomarkers & Prevention 16 (12):2795. doi: 10.1158/1055-9965.EPI-07-2543.
  • Moayeri, A., H. Niazi, and M. Darvishi. 2020. Effect of biocanin A in the acute phase of diffuse traumatic brain injury. International Journal of Pharmaceutical and Phytopharmacological Research 10:77–86.
  • Morgan, S., and R. W. Orrell. 2016. Pathogenesis of amyotrophic lateral sclerosis. British Medical Bulletin 119 (1):87–98. doi: 10.1093/bmb/ldw026.
  • Moriyama, M., A. Hashimoto, H. Satoh, K. Kawabe, M. Ogawa, K. Takano, and Y. Nakamura. 2018. S-equol, a major isoflavone from soybean, inhibits nitric oxide production in lipopolysaccharide-stimulated rat astrocytes partially via the GPR30-mediated pathway. International Journal of Inflammation 2018:1–8. doi: 10.1155/2018/8496973.
  • Moskot, M., S. Montefusco, J. Jakóbkiewicz-Banecka, P. Mozolewski, A. Węgrzyn, D. Di Bernardo, G. Węgrzyn, D. L. Medina, A. Ballabio, and M. Gabig-Cimińska. 2014. The phytoestrogen genistein modulates lysosomal metabolism and transcription factor EB (TFEB) activation. The Journal of Biological Chemistry 289 (24):17054–69. doi: 10.1074/jbc.M114.555300.
  • Murphy, M. P., and R. C. Hartley. 2018. Mitochondria as a therapeutic target for common pathologies. Nature Reviews. Drug Discovery 17 (12):865–86. doi: 10.1038/nrd.2018.174.
  • Nabi, M., and N. Tabassum. 2022. Role of environmental toxicants on neurodegenerative disorders. Frontiers in Toxicology 4:837579. doi: 10.3389/ftox.2022.837579.
  • Nagaraj, S., N. M N, and K. Pamidimukkala. 2017. Evaluation of in vitro cytotoxic effects of three medicinal plants on peripheral blood mononuclear cells (PBMC). Journal of Chemical and Pharmaceutical Research 9:18–26.
  • Nagarajan, S., S. Mohandas, K. Ganesan, B. Xu, and K. M. Ramkumar. 2022. New insights into dietary pterostilbene: Sources, metabolism, and health promotion effects. Molecules 27 (19):6316. doi: 10.3390/molecules27196316.
  • Nakai, S., M. Fujita, and Y. Kamei. 2020. Health promotion effects of soy isoflavones. Journal of Nutritional Science and Vitaminology 66 (6):502–7. doi: 10.3177/jnsv.66.502.
  • Nam, G., Y. Ji, H. J. Lee, J. Kang, Y. Yi, M. Kim, Y. Lin, Y. H. Lee, and M. H. Lim. 2019. Orobol: An isoflavone exhibiting regulatory multifunctionality against four pathological features of Alzheimer’s disease. ACS Chemical Neuroscience 10 (8):3386–90. doi: 10.1021/acschemneuro.9b00232.
  • Neal, J., P. B. Hutchings, C. Phelps, and D. Williams. 2022. Football and dementia: Understanding the link. Frontiers in Psychiatry 13:849876. doi: 10.3389/fpsyt.2022.849876.
  • Nebrisi, E. E. 2021. Neuroprotective activities of curcumin in Parkinson’s disease: A review of the literature. International Journal of Molecular Science 22:11248.
  • Nestor-Kalinoski, A., K. M. Smith-Edwards, K. Meerschaert, J. F. Margiotta, B. Rajwa, B. M. Davis, and M. J. Howard. 2022. Unique neural circuit connectivity of mouse proximal, middle, and distal colon defines regional colonic motor patterns. Cellular and Molecular Gastroenterology and Hepatology 13 (1):309–37.e3. doi: 10.1016/j.jcmgh.2021.08.016.
  • Newhouse, P., and J. Dumas. 2015. Estrogen-cholinergic interactions: Implications for cognitive aging. Hormones and Behavior 74:173–85. doi: 10.1016/j.yhbeh.2015.06.022.
  • Ninh The, S. 2017. A review on the medicinal plant dalbergia odorifera species: Phytochemistry and biological activity. Evidence-Based Complementary and Alternative Medicine 2017:7142370–27. doi: 10.1155/2017/7142370.
  • Occhiuto, F., G. Zangla, S. Samperi, D. R. Palumbo, A. Pino, R. De Pasquale, and C. Circosta. 2008. The phytoestrogenic isoflavones from Trifolium pratense L. (Red clover) protects human cortical neurons from glutamate toxicity. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 15 (9):676–82. doi: 10.1016/j.phymed.2008.04.007.
  • Okumura, N., H. Yoshida, Y. Nishimura, M. Murakami, Y. Kitagishi, and S. Matsuda. 2012. Genistein downregulates presenilin 1 and ubiquilin 1 expression. Molecular Medicine Reports 5 (2):559–61. doi: 10.3892/mmr.2011.648.
  • Onohuean, H., A. O. Akiyode, O. Akiyode, S. I. Igbinoba, and A. I. Alagbonsi. 2022. Epidemiology of neurodegenerative diseases in the East African region: A meta-analysis. Frontiers in Neurology 13:1024004. doi: 10.3389/fneur.2022.1024004.
  • Orhan, I., M. Kartal, F. Tosun, and B. Sener. 2007. Screening of various phenolic acids and flavonoid derivatives for their anticholinesterase potential. Zeitschrift Fur Naturforschung. C, Journal of Biosciences 62 (11-12):829–32. doi: 10.1515/znc-2007-11-1210.
  • Oseni, T., R. Patel, J. Pyle, and V. C. Jordan. 2008. Selective estrogen receptor modulators and phytoestrogens. Planta Medica 74 (13):1656–65. doi: 10.1055/s-0028-1088304.
  • Oza, M. J., and Y. A. Kulkarni. 2020. Formononetin ameliorates diabetic neuropathy by increasing expression of SIRT1 and NGF. Chemistry & Biodiversity 17 (6):e2000162. doi: 10.1002/cbdv.202000162.
  • Peirotén, Á., P. Gaya, I. Álvarez, and J. MALandete. 2020. Production of O-desmethylangolensin, tetrahydrodaidzein, 6’-hydroxy-O-desmethylangolensin and 2-(4-hydroxyphenyl)-propionic acid in fermented soy beverage by lactic acid bacteria and Bifidobacterium strains. Food Chemistry 318:126521. doi: 10.1016/j.foodchem.2020.126521.
  • Peng, Y., B. Jiang, H. Wu, R. Dai, and L. Tan. 2012. Effects of genistein on neuronal apoptosis, and expression of Bcl-2 and Bax proteins in the hippocampus of ovariectomized rats. Neural Regeneration Research 7 (36):2874–81. doi: 10.3969/j.issn.1673-5374.2012.36.004.
  • Pérez-Hernández, J., V. J. Zaldívar-Machorro, D. Villanueva-Porras, E. Vega-Ávila, and A. Chavarría. 2016. A potential alternative against neurodegenerative diseases: Phytodrugs. Oxidative Medicine and Cellular Longevity 2016:8378613–9. doi: 10.1155/2016/8378613.
  • Petrine, J. C. P., and B. Del Bianco-Borges. 2021. The influence of phytoestrogens on different physiological and pathological processes: An overview. Phytotherapy Research 35 (1):180–97. doi: 10.1002/ptr.6816.
  • Pierzynowska, K., L. Gaffke, A. Hać, J. Mantej, N. Niedziałek, J. Brokowska, and G. Węgrzyn. 2018. Correction of Huntington’s disease phenotype by genistein-induced autophagy in the cellular model. Neuromolecular Medicine 20 (1):112–23. doi: 10.1007/s12017-018-8482-1.
  • Pierzynowska, K., M. Podlacha, L. Gaffke, I. Majkutewicz, J. Mantej, A. Węgrzyn, M. Osiadły, D. Myślińska, and G. Węgrzyn. 2019. Autophagy-dependent mechanism of genistein-mediated elimination of behavioral and biochemical defects in the rat model of sporadic Alzheimer’s disease. Neuropharmacology 148:332–46. doi: 10.1016/j.neuropharm.2019.01.030.
  • Piscopo, P., M. Bellenghi, V. Manzini, A. Crestini, G. Pontecorvi, M. Corbo, E. Ortona, A. Carè, and A. Confaloni. 2021. A sex perspective in neurodegenerative diseases: MicroRNAs as possible peripheral biomarkers. International Journal of Molecular Science 22:4423.
  • Podbielska, M., N. L. Banik, E. Kurowska, and E. L. Hogan. 2013. Myelin recovery in multiple sclerosis: The challenge of remyelination. Brain Sciences 3 (3):1282–324. doi: 10.3390/brainsci3031282.
  • Pons, D. G., M. Nadal-Serrano, M. Torrens-Mas, J. Oliver, and P. Roca. 2016. The phytoestrogen genistein affects breast cancer cells treatment depending on the ERα/ERβ ratio. Journal of Cellular Biochemistry 117 (1):218–29. doi: 10.1002/jcb.25268.
  • Puri, V., N. Kanojia, A. Sharma, K. Huanbutta, D. Dheer, and T. Sangnim. 2022. Natural product-based pharmacological studies for neurological disorders. Frontiers in Pharmacology 13:1011740. doi: 10.3389/fphar.2022.1011740.
  • Purushothaman, B., and T. Sumathi. 2022. 5,6,7 Trihydroxy flavone armoured neurodegeneration caused by Quinolinic acid induced huntington’s like disease in rat striatum - reinstating the level of brain neurotrophins with special reference to cognitive-socio behaviour, biochemical and histopathological aspects. Neuroscience Research 174:25–35. doi: 10.1016/j.neures.2021.08.003.
  • Qin, H., Z. Lin, E. Vásquez, X. Luan, F. Guo, and L. Xu. 2019. High soy isoflavone or soy-based food intake during infancy and in adulthood is associated with an increased risk of uterine fibroids in premenopausal women: A meta-analysis. Nutrition Research 71:30–42. doi: 10.1016/j.nutres.2019.06.002.
  • Qu, Z., P. Tian, J. Zhao, G. Wang, and W. Chen. 2023. Feeding the microbiota–gut–brain axis: Nucleotides and their role in early life. Food Frontiers 4 (3):1164–78. doi: 10.1002/fft2.260.
  • Rabie, M. A., H. I. Ibrahim, N. N. Nassar, and R. M. Atef. 2023. Adenosine A(1) receptor agonist, N6-cyclohexyladenosine, attenuates Huntington’s disease via stimulation of TrKB/PI3K/Akt/CREB/BDNF pathway in 3-nitropropionic acid rat model. Chemico-Biological Interactions 369:110288. doi: 10.1016/j.cbi.2022.110288.
  • Radi, E., P. Formichi, C. Battisti, and A. Federico. 2014. Apoptosis and oxidative stress in neurodegenerative diseases. Journal of Alzheimers Disease 42 Suppl 3:S125–S152.
  • Raheja, S., A. Girdhar, A. Kamboj, V. Lather, and D. Pandita. 2021. Protective effect of dalbergia sissoo extract against amyloid-β (1-42)-induced memory impairment, oxidative stress, and neuroinflammation in rats. Turkish Journal of Pharmaceutical Science 18:104–10.
  • Rahman, M. H., J. Bajgai, A. Fadriquela, S. Sharma, T. T. Trinh, R. Akter, Y. J. Jeong, S. H. Goh, C.-S. Kim, and K.-J. Lee. 2021. Therapeutic potential of natural products in treating neurodegenerative disorders and their future prospects and challenges. Molecules 26 (17):5327. doi: 10.3390/molecules26175327.
  • Rajput, M. S., P. D. Sarkar, and N. P. Nirmal. 2017. Inhibition of DPP-4 activity and neuronal atrophy with genistein attenuates neurological deficits induced by transient global cerebral ischemia and reperfusion in streptozotocin-induced diabetic mice. Inflammation 40 (2):623–35. doi: 10.1007/s10753-017-0509-5.
  • Ramdath, D. D., E. M. Padhi, S. Sarfaraz, S. Renwick, and A. M. Duncan. 2017. Beyond the cholesterol-lowering effect of soy protein: A review of the effects of dietary soy and its constituents on risk factors for cardiovascular disease. Nutrients 9 (4):324. doi: 10.3390/nu9040324.
  • Reed, K. E., J. Camargo, J. Hamilton-Reeves, M. Kurzer, and M. Messina. 2021. Neither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studies. Reproductive Toxicology 100:60–7. doi: 10.1016/j.reprotox.2020.12.019.
  • Renko, K., S. Schäche, C. S. Hoefig, T. Welsink, C. Schwiebert, D. Braun, N.-P. Becker, J. Köhrle, and L. Schomburg. 2015. An improved nonradioactive screening method identifies genistein and xanthohumol as potent inhibitors of iodothyronine deiodinases. Thyroid 25 (8):962–8. doi: 10.1089/thy.2015.0058.
  • Rhaman, M. M., M. R. Islam, S. Akash, M. Mim, M. Noor Alam, E. Nepovimova, M. Valis, K. Kuca, and R. Sharma. 2022. Exploring the role of nanomedicines for the therapeutic approach of central nervous system dysfunction: At a glance. Frontiers in Cell and Developmental Biology 10:989471. doi: 10.3389/fcell.2022.989471.
  • Ribeiro, G., A. Ferri, G. Clarke, and J. F. Cryan. 2022. Diet and the microbiota - gut - brain-axis: A primer for clinical nutrition. Current Opinion in Clinical Nutrition and Metabolic Care 25 (6):443–50. doi: 10.1097/MCO.0000000000000874.
  • Rietjens, I., J. Louisse, and K. Beekmann. 2017. The potential health effects of dietary phytoestrogens. British Joural of Pharmacology 174:1263–80.
  • Roda, A. R., G. Serra-Mir, L. Montoliu-Gaya, L. Tiessler, and S. Villegas. 2022. Amyloid-beta peptide and tau protein crosstalk in Alzheimer’s disease. Neural Regeneraton Research 17:1666–74.
  • Rojas-García, A., Á. Fernández-Ochoa, M. L. Cádiz-Gurrea, D. Arráez-Román, and A. Segura-Carretero. 2023. Neuroprotective effects of agri-food by-products rich in phenolic compounds. Nutrients 15 (2):449. doi: 10.3390/nu15020449.
  • Russo, M., G. L. Russo, M. Daglia, P. D. Kasi, S. Ravi, S. F. Nabavi, and S. M. Nabavi. 2016. Understanding genistein in cancer: The "good" and the "bad" effects: A review. Food Chemistry 196:589–600. doi: 10.1016/j.foodchem.2015.09.085.
  • Sakshi, S., R. Jayasuriya, K. Ganesan, B. Xu, and K. M. Ramkumar. 2021. Role of circRNA-miRNA-mRNA interaction network in diabetes and its associated complications. Molecular Therapy. Nucleic Acids 26:1291–302. doi: 10.1016/j.omtn.2021.11.007.
  • Saleem, U., S. Khalid, Z. Chauhdary, F. Anwar, M. A. Shah, I. Alsharif, A. O. Babalghith, R. O. Khayat, A. E. Albalawi, T. A. S. Baokbah, et al. 2022. The curative and mechanistic acumen of curcuminoids formulations against haloperidol induced Parkinson’s disease animal model. Metabolic Brain Disease 38 (3):1051–66. doi: 10.1007/s11011-022-01122-1.
  • Schreihofer, D. A., and L. Redmond. 2009. Soy phytoestrogens are neuroprotective against stroke-like injury in vitro. Neuroscience 158 (2):602–9. doi: 10.1016/j.neuroscience.2008.10.003.
  • Simunkova, M., S. H. Alwasel, I. M. Alhazza, K. Jomova, V. Kollar, M. Rusko, and M. Valko. 2019. Management of oxidative stress and other pathologies in Alzheimer’s disease. Archives of Toxicology 93 (9):2491–513. doi: 10.1007/s00204-019-02538-y.
  • Singh, S., S. Grewal, N. Sharma, T. Behl, S. Gupta, M. K. Anwer, C. Vargas-De-La-Cruz, S. Mohan, S. G. Bungau, and A. Bumbu. 2023. Unveiling the pharmacological and nanotechnological facets of daidzein: Present state-of-the-art and future perspectives. Molecules 28 (4):1765. doi: 10.3390/molecules28041765.
  • Soltani, Z., M. Khaksari, E. Jafari, M. Iranpour, and N. Shahrokhi. 2015. Is genistein neuroprotective in traumatic brain injury? Physiology & Behavior 152 (Pt A):26–31. doi: 10.1016/j.physbeh.2015.08.037.
  • Song, Y. J., S. R. Li, X. W. Li, X. Chen, Z. X. Wei, Q. S. Liu, and Y. Cheng. 2020. The effect of estrogen replacement therapy on Alzheimer’s disease and parkinson’s disease in postmenopausal women: A meta-analysis. Frontiers in Neuroscience 14:157. doi: 10.3389/fnins.2020.00157.
  • Soni, M., T. B. W. Rahardjo, R. Soekardi, Y. Sulistyowati, Lestariningsih, A. Yesufu-Udechuku, A. Irsan, and E. Hogervorst. (2014). Phytoestrogens and cognitive function: A review. Maturitas 77 (3):209–20. doi: 10.1016/j.maturitas.2013.12.010.
  • Spencer, N. J., L. Travis, L. Wiklendt, M. Costa, T. J. Hibberd, S. J. Brookes, P. Dinning, H. Hu, D. A. Wattchow, and J. Sorensen. 2021. Long range synchronization within the enteric nervous system underlies propulsion along the large intestine in mice. Communications Biology 4 (1):955. doi: 10.1038/s42003-021-02485-4.
  • Srinivasan, S., J. Gal, A. Bachstetter, and P. T. Nelson. 2022. Alpha adaptins show isoform-specific association with neurofibrillary tangles in Alzheimer’s disease. Neuropathology and Applied Neurobiology 48 (2):e12776. doi: 10.1111/nan.12776.
  • Stanciu, G. D., A. Luca, R. N. Rusu, V. Bild, S. I. Beschea Chiriac, C. Solcan, W. Bild, and D. C. Ababei. 2019. Alzheimer’s disease pharmacotherapy in relation to cholinergic system involvement. Biomolecules 10 (1):40. doi: 10.3390/biom10010040.
  • Steinberg, F. M., M. J. Murray, R. D. Lewis, M. A. Cramer, P. Amato, R. L. Young, S. Barnes, K. L. Konzelmann, J. G. Fischer, K. J. Ellis, et al. 2011. Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women. The Americian Journal of Clinical Nutrition 93:356–67.
  • Stout, J. M., A. N. Knapp, W. J. Banz, D. G. Wallace, and J. L. Cheatwood. 2013. Subcutaneous daidzein administration enhances recovery of skilled ladder rung walking performance following stroke in rats. Behavioural Brain Research 256:428–31. doi: 10.1016/j.bbr.2013.08.027.
  • Subedi, L., E. Ji, D. Shin, J. Jin, J. H. Yeo, and S. Y. Kim. 2017. Equol, a dietary daidzein gut metabolite attenuates microglial activation and potentiates neuroprotection in vitro. Nutrients 9 (3):207. doi: 10.3390/nu9030207.
  • Sugimoto, M., R. Ko, H. Goshima, A. Koike, M. Shibano, and K. Fujimori. 2021. Formononetin attenuates H2O2-induced cell death through decreasing ROS level by PI3K/Akt-Nrf2-activated antioxidant gene expression and suppressing MAPK-regulated apoptosis in neuronal SH-SY5Y cells. Neurotoxicology 85:186–200. doi: 10.1016/j.neuro.2021.05.014.
  • Sukalingam, K., K. Ganesan, S. Das, and Z. C. Thent. 2015. An insight into the harmful effects of soy protein: A review. La Clinica Terapeutica 166 (3):131–9. doi: 10.7417/CT.2015.1843.
  • Tan, J. W., and M. K. Kim. 2016. Neuroprotective effects of biochanin A against β-amyloid-induced neurotoxicity in PC12 cells via a mitochondrial-dependent apoptosis pathway. Molecules 21 (5):548. doi: 10.3390/molecules21050548.
  • Tan, J. W., C. L. Tham, D. A. Israf, S. H. Lee, and M. K. Kim. 2012. Neuroprotective effects of biochanin A against glutamate-induced cytotoxicity in PC12 cells via apoptosis inhibition. Neurochemical Research 38 (3):512–8. doi: 10.1007/s11064-012-0943-6.
  • Tanaka, M., and H. Itoh. 2019. Hypertension as a metabolic disorder and the novel role of the gut. Current Hypertension Reports 21 (8):63. doi: 10.1007/s11906-019-0964-5.
  • Tao, J., Y. Cui, Y. Duan, N. Zhang, C. Wang, and F. Zhang. 2017. Puerarin attenuates locomotor and cognitive deficits as well as hippocampal neuronal injury through the PI3K/Akt1/GSK-3β signaling pathway in an in vivo model of cerebral ischemia. Oncotarget 8 (63):106283–95. doi: 10.18632/oncotarget.22290.
  • Tian, Z., S. B. Liu, Y. C. Wang, X. Q. Li, L. H. Zheng, and M. G. Zhao. 2013. Neuroprotective effects of formononetin against NMDA-induced apoptosis in cortical neurons. Phytotherapy Research 27 (12):1770–5. doi: 10.1002/ptr.4928.
  • Tousen, Y., M. Uehara, M. C. Kruger, and Y. Ishimi. 2012. Effects of dietary fibre and tea catechin, ingredients of the Japanese diet, on equol production and bone mineral density in isoflavone-treated ovariectomised mice. Journal of Nutritional Science 1:e13. doi: 10.1017/jns.2012.14.
  • Trieu, V. N., and F. M. Uckun. 1999. Genistein is neuroprotective in murine models of familial amyotrophic lateral sclerosis and stroke. Biochemical and Biophysical Research Communications 258 (3):685–8. doi: 10.1006/bbrc.1999.0577.
  • Turk, K. W., A. Geada, V. E. Alvarez, W. Xia, J. D. Cherry, R. Nicks, G. Meng, S. Daley, Y. Tripodis, B. R. Huber, et al. 2022. A comparison between tau and amyloid-β cerebrospinal fluid biomarkers in chronic traumatic encephalopathy and Alzheimer disease. Alzheimer’s Research & Therapy 14 (1):28. doi: 10.1186/s13195-022-00976-y.
  • Turknett, J., and T. R. Wood. 2022. Demand coupling drives neurodegeneration: A model of age-related cognitive decline and dementia. Cells 11 (18):2789. doi: 10.3390/cells11182789.
  • Tyagi, A. M., K. Srivastava, K. Sharan, D. Yadav, R. Maurya, and D. Singh. 2011. Daidzein prevents the increase in CD4 + CD28null T cells and B lymphopoesis in ovariectomized mice: A key mechanism for anti-osteoclastogenic effect. PloS one 6 (6):e21216. doi: 10.1371/journal.pone.0021216.
  • Uddin, M. S., and M. T. Kabir. 2019. Emerging signal regulating potential of genistein against Alzheimer’s disease: A promising molecule of interest. Frontiers in Cell and Developmental Biology 7:197. doi: 10.3389/fcell.2019.00197.
  • Uehara, M. 2013. Isoflavone metabolism and bone-sparing effects of daidzein-metabolites. Journal of Clinical Biochemistry and Nutrition 52 (3):193–201. doi: 10.3164/jcbn.13-2.
  • Umeno, A., M. Horie, K. Murotomi, Y. Nakajima, and Y. Yoshida. 2016. Antioxidative and antidiabetic Effects of natural polyphenols and isoflavones. Molecules 21 (6):708. doi: 10.3390/molecules21060708.
  • Valles, S. L., P. Dolz-Gaiton, J. Gambini, C. Borras, A. Lloret, F. V. Pallardo, and J. Viña. 2010. Estradiol or genistein prevent Alzheimer’s disease-associated inflammation correlating with an increase PPARγ expression in cultured astrocytes. Brain Research 1312:138–44. doi: 10.1016/j.brainres.2009.11.044.
  • Van Schependom, J., and M. D'Haeseleer. 2023. Advances in neurodegenerative diseases. Journal of Clinical Medicine 12 (5):1709. doi: 10.3390/jcm12051709.
  • Vasanthi Chinraj, and S. Raman. 2022. Neuroprotection by resveratrol: A review on brain delivery strategies for Alzheimer’s and Parkinson’s disease. Journal of Applied Pharmaceutical Science 12:01–17. doi: 10.7324/JAPS.2022.120701.
  • Velagapudi, R., O. O. Ajileye, U. Okorji, P. Jain, M. A. Aderogba, and O. A. Olajide. 2018. Agathisflavone isolated from Anacardium occidentale suppresses SIRT1-mediated neuroinflammation in BV2 microglia and neurotoxicity in APPSwe-transfected SH-SY5Y cells. Phytotherapy Research 32 (10):1957–66. doi: 10.1002/ptr.6122.
  • Vidyanti, A. N., M. T. N. Maulida Awaliyah, A. R. Fauzi, I. S. K. Harahap, and D. P. Mulya. 2022. Dementia in a patient with autoimmune disease and hypercoagulable state worsened by COVID-19 vaccination: A case report. Annals of Medicine and Surgery 78:103886. doi: 10.1016/j.amsu.2022.103886.
  • Wang, C., N. Xie, H. Zhang, Y. Li, and Y. Wang. 2014. Puerarin protects against β-amyloid-induced microglia apoptosis via a PI3K-dependent signaling pathway. Neurochemical Research 39 (11):2189–96. doi: 10.1007/s11064-014-1420-1.
  • Wang, H., X. Huang, S. Xia, X. Chen, C. Chen, Y. Zhang, J. Xiao, and S. Nie. 2022. Antagonistic effect of kale soluble dietary fiber and kale flavonoids, fails to alleviate colitis. Food Frontiers 4 (1):459–73. doi: 10.1002/fft2.191.
  • Wang, J., C. He, W. Y. Wu, F. Chen, Y. Y. Wu, W. Z. Li, H. Q. Chen, and Y. Y. Yin. 2015. Biochanin A protects dopaminergic neurons against lipopolysaccharide-induced damage and oxidative stress in a rat model of Parkinson’s disease. Pharmacology, Biochemistry, and Behavior 138:96–103. doi: 10.1016/j.pbb.2015.09.013.
  • Wang, J., L. Wang, J. Zhou, A. Qin, and Z. Chen. 2018. The protective effect of formononetin on cognitive impairment in streptozotocin (STZ)-induced diabetic mice. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 106:1250–7. doi: 10.1016/j.biopha.2018.07.063.
  • Wang, J. W., H. D. Wang, Z. X. Cong, X. M. Zhou, J. G. Xu, Y. Jia, and Y. Ding. 2014. Puerarin ameliorates oxidative stress in a rodent model of traumatic brain injury. The Journal of Surgical Research 186 (1):328–37. doi: 10.1016/j.jss.2013.08.027.
  • Wang, R., Y. Wei, W. Deng, and J. Teng. 2022. Pratensein mitigates oxidative stress and NLRP3 inflammasome activation in OGD/R-injured HT22 cells by activating Nrf2-anti-oxidant signaling. Neurotoxicity Research 40 (2):384–94. doi: 10.1007/s12640-022-00472-z.
  • Wang, S., J. Wang, H. Wei, T. Gu, J. Wang, Z. Wu, and Q. Yang. 2020. Genistein attenuates acute cerebral ischemic damage by inhibiting the NLRP3 inflammasome in reproductively senescent mice. Frontiers in Aging Neuroscience 12:153– doi: 10.3389/fnagi.2020.00153.
  • Wang, S., Y. Wang, M. H. Pan, and C. T. Ho. 2017. Anti-obesity molecular mechanism of soy isoflavones: Weaving the way to new therapeutic routes. Food & Function 8 (11):3831–46. doi: 10.1039/c7fo01094j.
  • Wang, S., H. Wei, M. Cai, Y. Lu, W. Hou, Q. Yang, H. Dong, and L. Xiong. 2014. Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice. International Journal of Biological Sciences 10 (4):457–65. doi: 10.7150/ijbs.7562.
  • Wang, W., S. Wang, Y. Liu, X. Wang, J. Nie, X. Meng, and Y. Zhang. 2022. Ellagic acid: A dietary-derived phenolic compound for drug discovery in mild cognitive impairment. Frontiers in Aging Neuroscience 14:925855. doi: 10.3389/fnagi.2022.925855.
  • Wang, X., Z. Yin, X. Meng, D. Yang, H. Meng, C. Liao, L. Wei, Y. Chen, X. Yang, J. Han, et al. 2022. Daidzein alleviates neuronal damage and oxidative stress via GSK3β/Nrf2 pathway in mice. Journal of Functional Foods 92:105060. doi: 10.1016/j.jff.2022.105060.
  • Wei, J., F. Yang, C. Gong, X. Shi, and G. Wang. 2019. Protective effect of daidzein against streptozotocin-induced Alzheimer’s disease via improving cognitive dysfunction and oxidative stress in rat model. Journal of Biochemical and Molecular Toxicology 33 (6):e22319. doi: 10.1002/jbt.22319.
  • Wei, L., S. Lv, Q. Huang, J. Wei, S. Zhang, R. Huang, Z. Lu, and X. Lin. 2015. Pratensein attenuates Aβ-induced cognitive deficits in rats: Enhancement of synaptic plasticity and cholinergic function. Fitoterapia 101:208–17. doi: 10.1016/j.fitote.2015.01.017.
  • Wen, Y., L. Zhang, N. Li, A. Tong, and C. Zhao. 2023. Nutritional assessment models for Alzheimer’s disease: Advances and perspectives. Food Frontiers 4 (2):624–40. doi: 10.1002/fft2.216.
  • Werner, M. H., and C. W. Olanow. 2022. Parkinson’s disease modification through Abl kinase inhibition: An opportunity. Movement Disorders 37 (1):6–15. doi: 10.1002/mds.28858.
  • Williams, A. J., and H. Umemori. 2014. The best-laid plans go oft awry: Synaptogenic growth factor signaling in neuropsychiatric disease. Frontiers in Synaptic Neuroscience 6:4. doi: 10.3389/fnsyn.2014.00004.
  • Wu, L. Y., Z. N. Ye, Z. Zhuang, Y. Gao, C. Tang, C. H. Zhou, C. X. Wang, X. S. Zhang, G. B. Xie, J. P. Liu, et al. 2018. Biochanin A reduces inflammatory injury and neuronal apoptosis following subarachnoid hemorrhage via suppression of the TLRs/TIRAP/MyD88/NF-κB pathway. Behavioural Neurology 2018:1960106–10. doi: 10.1155/2018/1960106.
  • Wu, Q. L., Y. Q. Cheng, A. J. Liu, and W. D. Zhang. 2020. Formononetin recovered injured nerve functions by enhancing synaptic plasticity in ischemic stroke rats. Biochemical and Biophysical Research Communications 525 (1):67–72. doi: 10.1016/j.bbrc.2020.02.015.
  • Wu, W., B. Niu, L. Peng, Q. Chen, H. Chen, H. Chen, W. Xia, L. Jin, J. Simal-Gandara, and H. Gao. 2023. Recent advances on the effect of nut consumption on cognitive improvement. Food Frontiers 4 (4):1737–46. doi: 10.1002/fft2.298.
  • Wu, X., H. Huang, M. Li, Y. Wang, X. Wu, Q. Wang, J. Shen, Z. Xiao, Y. Zhao, F. Du, et al. 2022. Excessive consumption of the sugar rich longan fruit promoted the development of nonalcoholic fatty liver disease via mediating gut dysbiosis. Food Frontiers 4 (1):491–510. doi: 10.1002/fft2.185.
  • Yan, X., A. Yu, H. Zheng, S. Wang, Y. He, and L. Wang. 2019. Calycosin-7-O-β-D-glucoside attenuates OGD/R-induced damage by preventing oxidative stress and neuronal apoptosis via the SIRT1/FOXO1/PGC-1α pathway in HT22 cells. Neural Plasticity 2019:8798069–11. doi: 10.1155/2019/8798069.
  • Yang, L., Y. Gao, M. A. Farag, J. Gong, Q. Su, H. Cao, W. Zhang, Y. Zhao, and H. Wang. 2023. Dietary flavonoids and gut microbiota interaction: A focus on animal and human studies to maximize their health benefits. Food Frontiers 4 (4):1794–809. doi: 10.1002/fft2.309.
  • Yang, L., Y. Gao, J. Gong, H. Wang, M. A. Farag, J. Simal-Gandara, Y. Zhao, S. Nie, and J. Xiao. 2022. Myricetin ameliorated prediabetes via immunomodulation and gut microbiota interaction. Food Frontiers 3 (4):749–72. doi: 10.1002/fft2.152.
  • Yang, Q., Z. H. Kang, J. Zhang, F. Qu, and B. Song. 2021. Neuroprotective effects of isoquercetin: An in vitro and in vivo study. Cell Journal 23:355–65.
  • Ye, S., T. T. Wang, B. Cai, Y. Wang, J. Li, J. X. Zhan, and G. M. Shen. 2017. Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase IV protein levels in Alzheimer’s disease model rats. Neural Regeneration Research 12 (9):1479–84. doi: 10.4103/1673-5374.215260.
  • Yong, S. J., A. Veerakumarasivam, W. L. Lim, and J. Chew. 2023. Neuroprotective effects of lactoferrin in Alzheimer’s and Parkinson’s diseases: A narrative review. ACS Chemical Neuroscience doi: 10.1021/acschemneuro.2c00679.
  • Youn, K., J. H. Park, J. Lee, W. S. Jeong, C. T. Ho, and M. Jun. 2016. The identification of biochanin a as a potent and selective β-site app-cleaving enzyme 1 (Bace1) inhibitor. Nutrients 8 (10):637. doi: 10.3390/nu8100637.
  • Yu, C. C., Y. J. Du, J. Li, Y. Li, L. Wang, L. H. Kong, and Y. W. Zhang. 2022. Neuroprotective mechanisms of puerarin in central nervous system diseases: Update. Aging and Disase 13:1092–105.
  • Yu, D., Y. Duan, Y. Bao, C. Wei, and L. An. 2005. Isoflavonoids from Astragalus mongholicus protect PC12 cells from toxicity induced by L-glutamate. Journal of Ethnopharmacology 98 (1-2):89–94. doi: 10.1016/j.jep.2004.12.027.
  • Yu, H. L., L. Li, X. H. Zhang, L. Xiang, J. Zhang, J. F. Feng, and R. Xiao. 2009. Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by beta-amyloid 31-35. The British Journal of Nutrition 102 (5):655–62. doi: 10.1017/S0007114509243042.
  • Yu, J., X. Bi, B. Yu, and D. Chen. 2016. Isoflavones: Anti-inflammatory benefit and possible caveats. Nutrients 8 (6):361. doi: 10.3390/nu8060361.
  • Yu, L., Y. Zhang, Q. Chen, Y. He, H. Zhou, H. Wan, and J. Yang. 2022. Formononetin protects against inflammation associated with cerebral ischemia-reperfusion injury in rats by targeting the JAK2/STAT3 signaling pathway. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 149:112836. doi: 10.1016/j.biopha.2022.112836.
  • Yuan, G., Y. Liu, G. Liu, L. Wei, Y. Wen, S. Huang, Y. Guo, F. Zou, and J. Cheng. 2019. Associations between semen phytoestrogens concentrations and semen quality in Chinese men. Environment International 129:136–44. doi: 10.1016/j.envint.2019.04.076.
  • Zahra, W., S. Rai, H. Birla, S. Singh, H. Dilnashin, A. Rathore, and S. Singh. 2020. The global economic impact of neurodegenerative diseases: Opportunities and challenges. In Bioeconomy for Sustainable Development. ed. C. Keswani, Singapore: Springer. doi: 10.1007/978-981-13-9431-7_17.
  • Zarmouh, N. O., S. K. Eyunni, and K. F. A. Soliman. 2017. The Benzopyrone Biochanin-A as a reversible, competitive, and selective monoamine oxidase B inhibitor. BMC Complementary and Aalternative Medicine. 17:34.
  • Zeng, H., Q. Chen, and B. Zhao. 2004. Genistein ameliorates beta-amyloid peptide (25-35)-induced hippocampal neuronal apoptosis. Free Radical Biology & Medicine 36:180–8.
  • Zgodova, A., S. Pavlova, A. Nekrasova, D. Boyarkin, V. Pinelis, A. Surin, and Z. Bakaeva. 2022. Isoliquiritigenin protects neuronal cells against glutamate excitotoxicity. Membranes 12 (11):1052. doi: 10.3390/membranes12111052.
  • Zhang, F., N. Ru, Z. H. Shang, J. F. Chen, C. Yan, Y. Li, and J. Liang. 2017. Daidzein ameliorates spinal cord ischemia/reperfusion injury-induced neurological function deficits in Sprague-Dawley rats through PI3K/Akt signaling pathway. Experimental and Therapeutic Medicine 14 (5):4878–86. doi: 10.3892/etm.2017.5166.
  • Zhang, H., Y. Chen, Z. Wang, G. Xie, M. Liu, B. Yuan, H. Chai, W. Wang, and P. Cheng. 2022. Implications of gut microbiota in neurodegenerative diseases. Frontiers in Immunology 13:785644. doi: 10.3389/fimmu.2022.785644.
  • Zhang, P., L. Zhang, L. Zhu, F. Chen, S. Zhou, T. Tian, Y. Zhang, X. Jiang, X. Li, C. Zhang, et al. 2015. The change tendency of PI3K/Akt pathway after spinal cord injury. Americian Journal of Translational Research 7:2223–32.
  • Zhang, Q., W. D. Huang, X. Y. Lv, and Y. M. Yang. 2012. Puerarin protects differentiated PC12 cells from H2O2-induced apoptosis through the PI3K/Akt signalling pathway. Cell Biology International 36 (5):419–26. doi: 10.1042/CBI20100900.
  • Zhang, S., Y. Sun, Q. Nie, J. Hu, W. Su, Z. Guo, Y. Zhang, and S. Nie. 2023. In vitro assessment of the effect of four polysaccharides on intestinal bacteria of mice with colitis. Food Frontiers 4 (3):1462–71. doi: 10.1002/fft2.270.
  • Zhang, W., Z. Wang, K. Ganesan, Y. Yuan, and B. Xu. 2022. Antioxidant activities of aqueous extracts and protein hydrolysates from marine worm hechong (Tylorrhynchus heterochaeta). Foods 11 (13):1837. doi: 10.3390/foods11131837.
  • Zhang, Y., and W.-A. Chen. 2014. Biochanin A inhibits lipopolysaccharide-induced inflammatory cytokines and mediators production in BV2 microglia. Neurochemical Research 40 (1):165–71. doi: 10.1007/s11064-014-1480-2.
  • Zhao, S. S., W. N. Yang, H. Jin, K. G. Ma, and G. F. Feng. 2015. Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. Neurotoxicology 51:166–71. doi: 10.1016/j.neuro.2015.10.010.
  • Zhao, Z., J. Fu, S. Li, and Z. Li. 2019. Neuroprotective effects of genistein in a SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis. Journal of Neuroimmune Pharmacology 14 (4):688–96. doi: 10.1007/s11481-019-09866-x.
  • Zheng, M., M. Zhou, M. Chen, Y. Lu, D. Shi, J. Wang, and C. Liu. 2021. Neuroprotective effect of daidzein extracted from Pueraria lobate Radix in a stroke model via the Akt/mTOR/BDNF channel. Frontiers in Pharmacology 12:772485. doi: 10.3389/fphar.2021.772485.
  • Zhou, J., L. Ding, W. Chen, and Y. Wang. 2023. Green tea catechin epigallocatechin gallate alleviates high-fat diet-induced obesity in mice by regulating the gut-brain axis. Food Frontiers 4 (3):1413–25. doi: 10.1002/fft2.252.
  • Zhu, G., X. Wang, S. Wu, X. Li, and Q. Li. 2014. Neuroprotective effects of puerarin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced Parkinson’s disease model in mice. Phytotherapy Research 28 (2):179–86. doi: 10.1002/ptr.4975.
  • Zhu, H., Y. Yan, Y. Jiang, and X. Meng. 2022. Ellagic acid and its anti-aging effects on central nervous system. International Journal of Molecular Science 23:10937.
  • Zhu, H., L. Zou, J. Tian, F. Lin, J. He, and J. Hou. 2014. Protective effects of sulphonated formononetin in a rat model of cerebral ischemia and reperfusion injury. Planta Medica 80 (4):262–8. doi: 10.1055/s-0033-1360340.
  • Zulhendri, F., C. O. Perera, and S. Tandean. 2021. Can propolis be a useful adjuvant in brain and neurological disorders and ­injuries? A systematic scoping review of the latest experimental evidence. Biomedicines 9 (9):1227. doi: 10.3390/biomedicines9091227.

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