Daidzein improves neuronal health and alleviates inflammation and apoptosis through BDNF and estrogen receptors in the hippocampus of ovariectomized rats

Isoflavone Daidzein (DDZ) has emerged as a promising alternative to hormone replacement therapy (HRT) for ameliorating estrogen deficiency (ED). However, the stereological and molecular mechanism of its effects in the OVX-hippocampus are unclear. We studied the impact of DDZ on stereological changes, estrogen receptor (ERs) expression, BDNF, GSK-3β, and inflammatory and apoptosis-related genes in the hippocampus of ovariectomized rats, compared to 17β-estradiol (E2).

OVX rats were treated with DDZ or E2. The stereological analysis assessed the total volume and number of pyramidal and granular neurons in the hippocampus CA1 and DG subregions. Expression of proinflammatory cytokines, apoptotic-related genes, ERs, and BDNF genes was evaluated using Real-Time PCR, and the GSK-3β phosphorylation level was measured by western blot analysis.

DDZ has effectively increased the volume and total number of pyramidal neurons in the CA1 region, the expression of ERα, ERβ, BDNF, and Bcl-2 genes, and the phosphorylation rate of GSK-3β protein. However, the effect of DDZ on the DG region, ERα, and BDNF genes was not significant in comparison with E2; DDZ significantly suppressed the expression of TNF-α, IL-6, and the Bax/Bcl2 ratio compared with OVX rats.

DDZ effectively reversed the stereological changes in the CA1 region by stimulating BDNF gene expression, increasing the phosphorylation ratio of the GSK-3β protein, and modulating inflammatory and apoptotic pathways. Although its effects on the DG region, BDNF, and ERα molecules were less significant than E2, DDZ could still be a promising candidate for ameliorating ED.