Pomegranate (Punica granatum) fruit is of particular interest because of its high nutritional value and therapeutic actions. Recently, we showed that an aqueous extract of pomegranate (AE-PG) given by oral route induced antidepressant-like actions mediated by estrogen receptors (ERs) suggesting its potential to function as an alternative to estrogen therapy replacement in menopause-related depression treatment.

Orally administered AE-PG allows the biotransformation of ellagitannins into active estrogenic compounds through the intestinal microbiota. However, it is necessary to know if compounds that do not need to be biotransformed by the intestinal microbiota are involved in the antidepressant-like effects. Therefore, the first aim of this study was to determine if AE-PG produces an antidepressant-like effect when administered intraperitoneally. Also, to determine the participation of specific ER-subtypes (α or β) and to analyze the role of the serotonergic system.

Young female Wistar rats were ovariectomized as a surgical model of menopause. The intraperitoneal administration of AE-PG (1 mg/kg; i. p.) was evaluated in the forced swimming test and open field tests. Also, the ERα antagonist (TPBM; 50 μg/rat; s. c.) or the ERβ antagonist (PHTPP; 25 μg/rat; s. c.) were administered with AE-PG to analyze the participation of the specific ERs. Finally, the effect of the serotonin neurotoxin 5,7-DHT (200 μg/rat; i. c.v.) on the antidepressant-like effect of the AE-PG was studied in independent experimental groups.

Results

showed that AE-PG administered by intraperitoneal route induced antidepressant-like effects. This result suggests that gut microbiota biotransformation is not necessary to exert its actions. The mechanism of action involves the activation of the ERβ and the serotonergic system. Altogether, this information contributes to the elucidation of the antidepressant action of the pomegranate fruit, which could be further considered as an alternative treatment for depression during menopause.

中文翻译：

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雌激素受体-β 和血清素介导石榴水提取物在去卵巢大鼠中的抗抑郁样作用

石榴（Punica granatum）果实因其高营养价值和治疗作用而受到特别关注。最近，我们发现石榴水提取物 (AE-PG) 通过口服途径诱导雌激素受体 (ER) 介导的抗抑郁样作用，表明其有潜力在更年期相关抑郁症治疗中替代雌激素疗法。

口服 AE-PG 允许鞣花单宁通过肠道微生物群生物转化为活性雌激素化合物。然而，有必要了解不需要通过肠道微生物群进行生物转化的化合物是否参与了抗抑郁样作用。因此，本研究的第一个目的是确定 AE-PG 在腹膜内给药时是否产生抗抑郁药样作用。此外, 确定特定 ER 亚型 (α 或β) 的参与, 并分析血清素系统的作用。

年轻的雌性 Wistar 大鼠被切除卵巢作为更年期的手术模型。AE-PG (1 mg/kg; ip) 的腹腔给药在强迫游泳试验和野外试验中进行了评估。此外，ERα拮抗剂（TPBM；50μg/大鼠；sc）或ERβ拮抗剂（PHTPP；25μg/大鼠；sc）与AE-PG一起施用以分析特定ER的参与。最后，在独立的实验组中研究了血清素神经毒素 5,7-DHT（200 μg/大鼠；icv）对 AE-PG 的抗抑郁样作用的影响。

结果

显示通过腹膜内途径施用的AE-PG诱导抗抑郁样作用。这一结果表明肠道微生物群的生物转化并不是发挥其作用所必需的。作用机制涉及激活 ERβ 和血清素系统。总而言之，这些信息有助于阐明石榴果实的抗抑郁作用，可以进一步将其视为更年期抑郁症的替代疗法。