The fluctuation in plasma estrogen level influences the cognitive function in the females. The specific estrogen receptor alpha (ERα) agonist, (4,4′,4″-(4-propyl-[1 H] pyrazole-1,3,5-triyl) tris phenol (PPT), is reported to exhibit therapeutic activity similar to that of estrogen replacement therapy. However, the former can also exert cyclic adenosine monophosphate (cAMP)-dependent carcinogenic activity in the uterus of the ovariectomized animals. Moreover, there is no report of cGMP on ERα-mediated phosphorylation of Akt in the experimental condition. Vinpocetine increases the rate of formation of cGMP than cAMP in several tissues. Hence, the present study evaluated the neuroprotective effect of vinpocetine with or without PPT against ovariectomy-induced dementia in experimental rodents. The condition of estrogen insufficiency was induced in female rats through bilateral ovariectomy on day-1 (D-1) of the experimental schedule. Vinpocetine (20 mg/kg) and PPT attenuated ovariectomy-induced cognitive deficits in behavioral tests and increase in body weight in the rodents. Vinpocetine and PPT increased the cholinergic function and the ratio of cGMP/cAMP in the hippocampus, pre-frontal cortex and amygdala of the ovariectomized animals. Further, ovariectomy-induced decrease in the extent of phosphorylation of ERα in all brain regions was attenuated with the monotherapy of either vinpocetine or PPT. Interestingly, the combination of vinpocetine and PPT exhibited better effectiveness than their monotherapy. However, vinpocetine attenuated the PPT-induced increased level of phosphorylated Akt in discrete brain regions and weight of uterus of these rodents. Hence, the combination could be considered as a better alternative candidate with minimal side effects in the management of estrogen insufficiency-induced disorders.

血浆雌激素水平的波动影响女性的认知功能。据报道，特定的雌激素受体 α (ERα) 激动剂 (4,4',4"-(4-propyl-[1 H] pyrazole-1,3,5-triyl) tris phenol (PPT)) 具有治疗活性与雌激素替代疗法相似，但前者也可在去卵巢动物的子宫内发挥依赖环磷酸腺苷（cAMP）的致癌活性。实验条件。长春西汀在几种组织中比 cAMP 增加了 cGMP 的形成率。因此，本研究评估了长春西汀有或没有 PPT 对实验啮齿动物卵巢切除引起的痴呆的神经保护作用。在实验计划的第 1 天 (D-1) 通过双侧卵巢切除术在雌性大鼠中诱导雌激素不足的情况。长春西汀 (20 mg/kg) 和 PPT 减轻了卵巢切除术引起的行为测试中的认知缺陷和啮齿动物体重的增加。长春西汀和 PPT 增加了去卵巢动物的海马、前额叶皮层和杏仁核中的胆碱能功能和 cGMP/cAMP 的比率。此外，长春西汀或 PPT 的单一疗法减弱了卵巢切除术引起的所有大脑区域中 ERα 磷酸化程度的降低。有趣的是，长春西汀和 PPT 的组合比它们的单一疗法表现出更好的有效性。然而，长春西汀减弱了 PPT 诱导的这些啮齿动物离散大脑区域和子宫重量中磷酸化 Akt 水平的增加。因此，在治疗雌激素不足引起的疾病方面，该组合可被视为具有最小副作用的更好的替代候选者。