Aqueous Extract of Pomegranate Alone or in Combination with Citalopram Produces Antidepressant-Like Effects in an Animal Model of Menopause: Participation of Estrogen Receptors

Abstract

It has been reported that the aqueous extract of pomegranate (AE-PG) has polyphenols with estrogenic-like activities. The present work determines if AE-PG alone or in combination with the selective serotonin reuptake inhibitor, citalopram, has antidepressant-like effects. It was also analyzed the participation of estrogen receptors (ER). AE-PG (0.1, 1.0, 10, or 100 mg/kg) was evaluated in ovariectomized female Wistar rats subjected to the forced swimming test. The effects induced by AE-PG were compared with those of citalopram (2.5, 5.0, 10, and 20.0 mg/kg) and 17β-estradiol (E2; 2.5 5.0, and 10 μg/rat). Likewise, the combination of suboptimal doses of AE-PG (0.1 mg/kg) plus citalopram (2.5 mg/kg) was evaluated. To determine if ER participates in the antidepressant-like action of pomegranate, the estrogen antagonist tamoxifen (15 mg/kg) was administered with AE-PG (1 mg/kg). AE-PG produced antidepressant-like actions with a similar behavioral profile induced by citalopram and E2. Suboptimal doses of citalopram plus AE-PG produced antidepressant-like effects. Tamoxifen was able to block AE-PG’s antidepressant-like actions. These results confirm the participation of ER in AE-PG’s antidepressant-like effects. Furthermore, the additive effects observed with the combined treatment of AE-PG plus citalopram could be advantageous in the treatment of depressive disorders, such as menopause.

Antidepressant effect of methanol extract of smokeless tobacco and identification of its bioactive components

“…Acute dosing of majority of antidepressants reduces immobility time in TST model. The immobility displayed by experimental rats in these models is a measure of behavioral despair which is synonymous with depression [19,20]. These results suggest that nicotine possesses antidepressant and mood-elevating properties, since nicotine was identified as one of the major bioactive compound in the extract.…”

Pomegranate and Its Components, Punicalagin and Ellagic Acid, Promote Antidepressant, Antioxidant, and Free Radical-Scavenging Activity in Ovariectomized Rats

“…Hence, finding new drugs for the treatment of depression is highly necessary (Girish et al, 2012). Furthermore, some of the new drugs with antidepressant actions also possess antioxidant properties, which reinforces the notion of the relationship between oxidative stress and depressive disorders (Mori-Okamoto et al, 2004;Naveen et al, 2013;Valdés-Sustaita et al, 2017Moore et al, 2018;Estrada-Camarena et al, 2020;Ruiz-Sánchez et al, 2020).…”

“…AEPG induced an antidepressant-like action after a subacute (Valdés-Sustaita et al, 2021) or chronic schedule of administration (Valdés-Sustaita et al, 2017). In addition, AEPG reduced the immobility behavior after an oral or intraperitoneal route of administration (Valdés-Sustaita et al, 2017, suggesting that their actions do not necessarily require the first step's metabolism. In fact, its mechanism of action appears to be related to the activation of the estrogen receptor β, participation of the serotoninergic system, and the peroxisome proliferator-activated receptor (PPARγ) (Valdés-Sustaita et al, 2017Estrada-Camarena et al, 2020); however, its activity as an antioxidant in ovariectomized rats is unknown.…”

“…Recently, the antidepressant and anxiolytic-like actions of an aqueous extract of P. granatum enriched with ellagitanins (AEPG) were assessed in female rats (Estrada-Camarena et al, 2020). AEPG induced an antidepressant-like action after a subacute (Valdés-Sustaita et al, 2021) or chronic schedule of administration (Valdés-Sustaita et al, 2017). In addition, AEPG reduced the immobility behavior after an oral or intraperitoneal route of administration (Valdés-Sustaita et al, 2017, suggesting that their actions do not necessarily require the first step's metabolism.…”

Chronic Stress and Gonadectomy Affect the Expression of Cx37, Cx40 and Cx43 in the Spinal Cord

“…One group of female rats (N = 12) was ovariectomized, one group of male rats (n = 10) was orchidectomized, and the other animals were sham-operated (SH). Ovariectomy of female rats was made by a midline abdominal incision [30], while male rats were castrated according to the method of Idris [31]. Two months after the surgery (age 15 months), all stress caused by surgery was considered irrelevant based on previous research where it was described that at least 4 weeks are required between surgery and exposure to chronic stress protocol [32].…”