Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice
Introduction
The pomegranate tree, which is said to have flourished in Eden, has been used extensively in the folk medicine for a number of therapeutic purposes (Langley, 2000). Pomegranate is a rich source of crude fibers, pectin, sugars, and several tannins (Gil et al., 2000). In addition, it has recently been reported that pomegranate contains some species of flavonoids and anthocyanidins in their seed oil and juice, and shows an antioxidant activity three times more potently than red wine and green tea extract (Schubert et al., 1999, Gil et al., 2000, Aviram et al., 2000, Aviram and Dornfeld, 2001, Kaplan et al., 2001, Halvorsen et al., 2002, Noda et al., 2002, Singh et al., 2002). Furthermore, the chemopreventive and adjuvant therapeutic applications of pomegranate to human breast cancer have been warranted recently (Kim et al., 2002). Owing to these significant biological activities, pomegranate juice is being increasingly popularized in Japan.
However, one of the most remarkable characteristics of pomegranate fruit is that its seeds are the richest plant source of estrogens. Pomegranate seeds are known to contain the estrogenic compounds, estrone and estradiol, that are chemically identical to those biosynthesized in human body (Heftmann et al., 1966), and coumesterol as well (Moneam et al., 1988). According to Kim et al. (2002), pomegranate seeds contain not only estrogens (estradiol, estrone, and estriol) but also other steroids such as testosterone and β-sitosterol, and coumesterol, whereas, anthocyanins and phenolic acids are the main ingredients of pomegranate juice. In our preliminary HPLC assay, isoflavone phytoestrogens such as genistein and daidzein were also detected in the pomegranate extract containing seeds used in this study. The estrogenic activities of pomegranate seed extract on the uterus weight and vaginal smears have already been investigated in ovariectomized animals (Sharaf and Nigm, 1964). Then, the question raised is whether pomegranate can, as the richest plant source of estrogens, exhibit additional important biological actions on menopausal syndrome in women? This question prompted us to investigate the effect of “pomegranate extract” (see Section 2 for the property of “pomegranate extract”) on the estrogen deficiency produced by bilateral ovariectomy of experimental animals.
A depressive state is a clinically significant mental profile of human menopausal syndrome (Gerdes et al., 1982). A forced swimming test is considered to be useful for experimentally investigating a depressive state in humans because the behavioral immobility of mice or rats which occurs during forced swimming has been reported to be able to reproduce some aspects of human depression (Porsolt et al., 1977, Yoshimura and Yamakawa, 2000). A depressive animal is liable to despair of escaping from forced swimming and become immobile. In fact, ovariectomized mice have been confirmed to show not only a prolonged immobility time in forced swimming test but also regional skin temperature changes alike a hot-flush symptom in women (Okada et al., 1997).
Another characteristic of menopausal syndrome is bone loss. Involutional bone loss in post-menopausal women has been suggested to occur in the two phases: an early rapid phase beginning at menopause and lasting for 6–10 years; and a subsequent slow phase lasting for the rest of a woman’s life (Riggs et al., 1998). It is also known that estrogen replacement therapy can prevent the early phase of involutional bone loss from occurring and also restore the rate of bone resorption and formation to pre-menopausal levels in menopausal women (Barzel, 1988, Heshmati et al., 2002). Thus, it is clear that the menopausal bone loss is attributable to the cessation of ovarian function and tapering-off of estrogen secretion. On this basis, we also investigated the effects of the pomegranate extract on bone properties by measuring the mineral bone density and some histological parameters of bone turnover.
We report here that the pomegranate extract is pharmacologically effective on the menopausal symptoms produced in mice by bilateral ovariectomy and finally propose that the daily regular consumption of juice from whole pomegranate fruit can protect women from a variety of menopausal syndromes.
Section snippets
The pomegranate extract used
The pomegranate extract used in this study was produced and blended under license in Iran and distributed in Japan by Perusha Zakuro Co. Ltd. (Tokyo, Japan), and contained both the seed and juice of the four Persian black and red pomegranate species, Siyah Daneh Dorosht Shiraz, Tough Gardan Shahvar, Malas Shirin Yazd, and Tabolarz Dorosht Shiraz. This pomegranate seed extract and juice (pomegranate extract, hereafter) had been confirmed to contain estrogens (estradiol, estrone, and estriol),
Effects on the body weight and uterus weight
The mean values of body weight and uterus weight of intact and ovariectomized mice (n=10 for each) measured after the 2-week administration of 5% glucose solution or pomegranate extract are shown in Table 1 and Fig. 1. As shown in Table 1 and Fig. 1, the mean body weight was 34.1±0.8 g in 5% glucose-dosed ovariectomized mice (control group) which was significantly greater than that in intact mice, 32.2±1.4 g (P<0.01). However, this ovariectomy-induced increase in body weight was abolished by the
Discussion
It is well known that ovariectomy induces the increase of body weight (Wade, 1979, Yoshimura and Kan, 1998). Also in the present study, the body weight of mice increased after bilateral ovariectomy, and the increase was inhibited by chronic administration of pomegranate extract.
Regarding the role of estrogens in lipid metabolism, estrogen insufficiency is thought to be largely responsible for an increase in adiposity during menopause because postmenopausal women under estrogen replacement
Acknowledgements
This work was supported in part by the MOA Health Science Foundation.
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