The cognitive function in the females is observed to modulate with the fluctuation in plasma estrogen level. The specific estrogen receptor alpha (ERα) agonist, (4,4',4″-(4-propyl-[1H] pyrazole-1,3,5-triyl) tris phenol (PPT), exerts similar therapeutic activity to that of estrogen replacement therapy. It can also exert cyclic adenosine monophosphate (cAMP)-dependent carcinogenic activity in the uterus of the ovariectomized animals. However, there is no report of cGMP on the ERα-mediated phosphorylation of Akt in the experimental condition. Sildenafil increases the level of cGMP in most of the tissues including brain. Hence, the present study evaluated the therapeutic effect of Sildenafil with or without PPT in rats with experimentally-induced estrogen insufficiency. The condition of estrogen insufficiency was induced in female rats through bilateral ovariectomy on day-1 (D-1) of the experimental schedule. Sildenafil (1.0 and 10.0 mg/kg) and PPT attenuated ovariectomy-induced cognitive deficits in behavioural tests and increase in body weight in the rodents. Sildenafil and PPT increased the cholinergic function and the ratio of cGMP/cAMP in the hippocampus, pre-frontal cortex and amygdala of the animals. Further, the ovariectomy-induced decrease in the extent of phosphorylation of ERα in all the brain regions was attenuated with the monotherapy of either Sildenafil or PPT. Interestingly, the combination of Sildenafil and PPT exhibited better therapeutic effectiveness than their monotherapy. However, Sildenafil attenuated the PPT-induced increase in the level of expression of phosphorylated protein kinase-B (Akt) in the discrete brain regions and the weight of uterus of these rodents. Hence, it can be assumed that the combination could be a better therapeutic alternative with minimal side effect in the management of estrogen insufficiency-induced disorders.

中文翻译：

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西地那非可在雌激素不足的动物中促进雌激素受体α激动剂的抗遗忘活性。

观察到女性的认知功能随血浆雌激素水平的波动而调节。特异性雌激素受体α（ERα）激动剂（4,4'，4“-（4-丙基-[1H]吡唑-1,3,5-三基）三酚（PPT）具有与雌激素替代疗法，它还可以在卵巢切除动物的子宫中发挥环磷酸腺苷（cAMP）依赖性的致癌活性，但是，在实验条件下，尚无cGMP对ERα介导的Akt磷酸化的报道。因此，本研究评估了西地那非联合或不联合PPT对实验性雌激素功能不全大鼠的治疗作用。在实验时间表的第1天（D-1），通过双侧卵巢切除术在雌性大鼠中诱发雌激素功能不全。西地那非（1.0和10.0 mg / kg）和PPT减轻了行为测试中卵巢切除术引起的认知缺陷，并减轻了啮齿动物的体重。西地那非和PPT可增加动物海马，前额叶皮层和杏仁核中胆碱能功能和cGMP / cAMP的比例。此外，西地那非或PPT的单药治疗可减轻卵巢切除术引起的所有脑区域ERα磷酸化程度的降低。有趣的是，西地那非和PPT的组合显示出比其单一疗法更好的治疗效果。然而，西地那非减弱了PPT诱导的离散型鼠脑区域磷酸化蛋白激酶B（Akt）表达水平的增加以及这些啮齿动物的子宫重量。因此，可以假设在雌激素不足引起的疾病的治疗中，该组合可以是具有最小副作用的更好的治疗选择。