COULD AGLYCONE-RICH SOY EXTRACTS EXERT A NEUROPROTECTIVE ROLE IN MICROGLIAL CELLS?

Soy isoflavones have been extensively investigated for their potential health benefits. These naturally occurring compounds, found in soy-based foods, share structural similarities with estrogen and are commonly consumed by menopausal women as a natural alternative to hormone therapy. Consequently, their potential neuroprotective effects and possible role in mitigating menopause-associated neuroinflammation and mental health disorders have attracted considerable interest.

This study aimed to evaluate the effects of aglycone-rich soy extracts on the expression of pro-inflammatory markers associated with the M1-like microglial phenotype using an in vitro cell model. Given the critical role of microglia in modulating neuronal synaptic structures, the study also investigated synapsin I expression in neuronal cells exposed to microglia-conditioned medium.

Two experiments were conducted. First, lipopolysaccharide (LPS)-stimulated N9 microglial cells were treated with four isoflavone-rich extracts (S1, S2, S3, and S4) or 17β-estradiol at different concentrations to assess the mRNA expression of key pro-inflammatory markers (TNF-α, IL-1β, IL-6, iNOS, and MCP1) via real-time PCR. Second, SH-SY5Y neuroblastoma cells were exposed to microglia-conditioned medium to evaluate potential effects on synapsin I expression.

Treatment with the aglycone-rich extract S3 significantly downregulated IL-1β and TNF-α mRNA expression by 2.8-fold and 3.1-fold, respectively, compared with the LPS-stimulated control, performing comparably to ‒ and in several instances exceeding the efficacy of ‒ 17β-estradiol hormone. In contrast, the non-biotransformed control extract (SC) significantly upregulated iNOS and MCP1 expression by 5.5-fold and 1.7-fold, respectively, indicating a potential pro-inflammatory effect. No detectable modulation of synapsin I expression was observed in the neuron–microglia experimental model under the tested conditions.

These findings highlight the anti-inflammatory potential of aglycone-rich soy extracts, particularly S3, in microglial cells and suggest that biotransformation may influence the immunomodulatory properties of soy isoflavones. Further studies are warranted to elucidate their underlying neuroprotective mechanisms.

Acknowledgments:

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [Programa de Doutorado Sanduíche no Exterior – PDSE; process number 88881.134558/2016-01 – fellowship grant]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [grant number 17367-7, 2014]