4.1 Article

Daidzein Attenuates Ovariectomy-Induced Cognitive Deficits by Improving Cortical Endothelial Function in Rats

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DOI: 10.1007/s43450-023-00425-3

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Acetylcholine; Cortex; Estrogen; Isoflavone; Memory; Vascular function

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The study investigates the potential neuroprotective and anti-amnesic effects of daidzein, a phytoestrogen derived from plants, on ovariectomized rats. The results show that daidzein can attenuate cognitive deficits induced by ovariectomy through the caveolin-1/eNOS/VEGF-mediated signaling pathway, making it a potential therapeutic option for the treatment of cognitive deficits in postmenopausal women.
There have been reports of decreased vascular activity in memory-sensitive brain areas, which is thought to be a different approach to managing cognitive deficiencies in females with estrogen insufficiency. Daidzein, a plant-derived phytoestrogen, facilitates cerebral blood flow in normal animals and also improves vascular activity in the peripheral tissues of the ovariectomized animal. However, its neuroprotective activity in vascular function has not yet been established in ovariectomized animals. Hence, the present study explored the caveolin-1/eNOS/VEGF-mediated signaling in the anti-amnesic ability of daidzein in ovariectomized rats. On day 5 of the Morris water maze experiment, female rats with bilateral ovariectomy displayed amnesia as measured by an increase in both escape latency and time spent in the targeted quadrant. Further, ovariectomy reduced blood flow and the level of expression of vascular endothelial growth factor in rat cortical tissues. In addition, ovariectomy diminished the acetylcholine level, increased the acetylcholinesterase activity, and increased oxidative stress in rat cortical tissues. Daidzein attenuated ovariectomy-induced alterations in behavioral, vascular, cholinergic, and oxidative stress in the animals. These beneficial effects of daidzein were abolished with N-nitro-l-arginine methylester (L-NAME), which inhibits endothelial nitric oxide synthase, in the ovariectomized rat model. These observations emphasize the fact that daidzein potentially exerts anti-amnesic activity perhaps through the caveolin-1/eNOS/VEGF-mediated signaling pathway in ovariectomy-induced cognitive-deficit rats. Therefore, daidzein holds the potential as a therapeutic option for the treatment of cognitive deficits in postmenopausal women.

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