Daidzein's potential in halting neurodegeneration: unveiling mechanistic insights

Neurological conditions encompassing a wide range of disorders pose significant challenges globally. The complex interactions among signaling pathways and molecular elements play pivotal roles in the initiation and progression of neurodegenerative diseases. Isoflavones have emerged as a promising candidate to fight against neurodegenerative diseases. Daidzein, a 7-hydroxy-3-(4-hydroxyphenyl)-chromen-4-one, belongs to the isoflavone class and exhibits a diverse pharmacological profile. It is found primarily in soybeans and soy products, as well as in some other legumes and herbs. Investigations into daidzein have revealed that it confers neuroprotection by inhibiting oxidative stress, inflammation, and apoptosis, which are key contributors to neuronal damage and degeneration. Activating pathways like PI3K/Akt/mTOR and promoting neurotrophic factors like BDNF by daidzein underscore its potential in supporting neuronal function and combating neurodegeneration. Daidzein's effects on dopamine provide further avenues for intervention in conditions like Parkinson's disease. Additionally, the modulation of inflammatory and NRF-2-antioxidant signaling by daidzein reinforces its neuroprotective role. Moreover, daidzein's interaction with receptors and cellular processes like ER-β, GPR30, MAO, VEGF, and GnRH highlights its multifaceted effects across multiple pathways involved in neuroprotection and neuronal function. This review article delves into the mechanistic interplay of various mediators in mediating the neuroprotective effects of daidzein. The review article consolidates and analyzes research published over nearly two decades (2005-2024) from various databases, including PubMed, Scopus, ScienceDirect, and Web of Science, to provide a comprehensive understanding of daidzein's effects and mechanisms in neuroprotection.