β-Amyloid Formation, Memory, and Learning Decline Following Long-term Ovariectomy and Its Inhibition by Systemic Administration of Apigenin and β-Estradiol

INTRODUCTION: The increasing cases of Alzheimer Disease (AD) has caused numerous problems. The risk of developing AD increases in menopausal women, too. Apigenin and β-estradiol are effective antioxidant and neuroprotective agents. We conducted the present study to explore their combined effects on β-amyloid plaque formation, memory, and learning in ovariectomized rats. METHODS: Forty-two Wistar rats were randomly assigned into 6 groups: 1) ovariectomized (OVX), 2) OVX + apigenin, 3) OVX + β-estradiol, 4) OVX + apigenin + β-estradiol, 5 &6) vehicle shams for E2 and API, and 7) surgical sham. Treatment was done with apigenin and β-estradiol. Then, we studied the formation of β-amyloid plaques, neuronal density in the hippocampus area, apoptosis, memory, and learning. RESULTS: Findings showed the significant formation of β-amyloid plaques in the hippocampus of OVX animals and their memory impairment. Apigenin and β-estradiol significantly reduced the number of β-amyloid plaques, as well as the symptoms of memory impairment and learning, and decreased the expression of caspase-3 in treated animals. CONCLUSION: Accordingly, β-estradiol and apigenin could have more potent therapeutic effects on AD.