Estrogenic Effects of Pueraria mirifica on the Menstrual Cycle and Hormone-Related Ovarian Functions in Cyclic Female Cynomolgus Monkeys

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Abstract. The aim of this study was to evaluate the estrogenic activity of tuberous samples of phytoestrogen-rich Pueraria mirifica collected from 25 of 76 provinces in Thailand by vaginal cornification assay. Tuberous powders were prepared and administered to ovariectomized rats for 14 consecutive days at dosages of 10, 100 and 1,000 mg/kg BW respectively, and were compared with a daily treatment with 2 mg/kg BW 17β-estradiol (E2). Rats treated with 10 mg/kg BW Pueraria mirifica showed no vaginal cornification. Treatment with 100 mg/kg BW Pueraria mirifica from 13 out of 25 plant samples resulted in development of vaginal cornification. The cell count percentages of the vaginal smeared cells for the treatment with the 2 plant samples that exhibited the fastest vaginal cornification revealed large variation in their estrogenic activities. Treatment with 1,000 mg/kg BW Pueraria mirifica from all plant samples produced vaginal cornification with the mean value for the period (day) of first appearance of cornified cells being 4.08 days compared to 2 days with 2 mg/kg BW E2. The overall appearance period (day) of cornified cells during the treatment and post-treatment period with 1,000 mg/kg BW per day Pueraria mirifica was shorter than treatment with 2 mg/kg BW E2. The results demonstrate that the plant population shows differential estrogenic activity as evaluated by vaginal cornification assay. , and isoflavones [5][6][7][8][9][10]. The estrogenic activity of miroestrol was first determined in ovariectomized rats. Administration of miroestrol produces a mammogenic effect in rats [11]. Using the vaginal cornification assay, miroestrol was estimated to have 0.25 times the estrogenic activity of 17β-estradiol [12]. Thus, various types of research have been conducted on the estrogenic effects of P. mirifica, especially in recent years. Crude P. mirifica powder can relief the climacteric symptoms of post-menopausal women [13]. The estrogenic activities of P. mirifica powder and extract has been evaluated in various species of experimental animals and found to have no toxicity [14]. P. mirifica has biphasic effects on MCF-7 cell proliferation, both suppression and stimulation [15], and an anti-proliferation effect on HeLa cells (ERα-negative human cervical adenocarcinoma cells) [16]. Considering the effects on the reproductive organs and reproductive-related hormones, P. mirifica suppresses luteinizing

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Evaluation of the Estrogenic Activity of the Wild Pueraria mirifica by Vaginal Cornification Assay

Cherdshewasart

Kitsamai

Malaivijitnond

2007

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“…The phytoestrogens of P. mirifica exhibit the following responses: dose-dependent estrogenic effects on the reproductive system, initiated vaginal cornification, increased uterine weight with decreased follicle stimulating hormone (FSH) and luteinizing hormone (LH) serum levels in ovariectomized rats [8], increased length of the follicular phase and total menstruation cycle [9], decreased estrogen, progesterone, FSH, and LH concentrations at the dose of 1,000 mg/kg BW [10], and ovulation blockage in female monkeys [11]. In aged menopausal monkeys, consumption of crude powder from the plant decreases the concentrations of FSH and LH [12] and parathyroid hormone (PTH) [13] and induces reappearance of sexual skin [14].…”

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confidence: 99%

Determination of the Estrogenic Activity of Wild Phytoestrogen-rich Pueraria mirifica by MCF-7 Proliferation Assay

Cherdshewasart

Traisup

Picha³

2008

Abstract. The aim of this study was to evaluate the estrogenic activity of tuberous samples of wild, phytoestrogen-rich Pueraria mirifica collected from 28 out of 76 provinces of Thailand by MCF-7 proliferation assay. The plant extracts were administered to MCF-7, ERα positive human mammary adenocarcinoma cell cultures, for 3 days at dosages of 0.1, 1, 10, 100 and 1,000 µg/ml and were compared with 17β-estradiol at concentrations of 10 -12 -10 -6 M. The mean P. mirifica population at 1 µg/ml exhibited significant proliferation. Two plant samples exhibited levels of proliferation in MCF-7 that were similar to 17β-estradiol. The mean P. mirifica populations at 100 and 1,000 µg/ml exhibited significant cytotoxicity in MCF-7. Analysis of the estrogenic activity of puerarin, representative of major isoflavonoids in P. mirifica tubers, revealed proliferation in MCF-7 only at the highest dose (10 -6 M) that was 10 2 -10 5 times less active than 17β-estradiol. Puerarin and 17β-estradiol at concentration of 10 -12 -10 -6 M exhibited no cytotoxicity in MCF-7. Key words: Isoflavonoid, MCF-7 proliferation assay, Phytoestrogen, Pueraria mirifica, Puerarin (J. Reprod. Dev. 54: [63][64][65][66][67] 2008) he plants in genus Pueraria are largely distributed in Asia and have a long history of ethnopharmacological applications [1]. Pueraria mirifica Airy Shaw et Suvatabhandu, family Leguminosae, is an indigenous Thai herb. The potent estrogenic activity of the plant has been proven in a 1-year human clinical trial of 4 menopausal volunteers at Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Bangkok, Thailand. An average dose of 100 mg of tuberous powder per day was effective for long-term treatment of menopausal symptoms [2], and toxicological tests showed that it did not have significant adverse effects in animals and human volunteers. An acute toxicity test of P. mirifica treatment at a dose of 16 g/kg BW using rats did not reveal any adverse effects [3]. However, P. mirifica did initiate adverse effects such as anemia, during subchronic treatment for 3 months at doses of 100 and 1,000 mg/kg BW [4]. Haemotological adverse effects were confirmed in a 6-month chronic toxicity test at a dose of 250 mg/kg BW [5]. Treatment with the plant extract at high doses 600 and 800 mg/kg BW, for 30 days induces micronucleus formation in male rats [6]. However, pretreatment of weanling rats with P. mirifica powder at a dose of 10, 100 and 1,000 mg/kg BW for 28 days resulted in a dose-dependent prevention of mammary tumors induced by 7, 12-dimethylbenz (a) anthracene (7, 12-DMBA) [7].The phytoestrogens of P. mirifica exhibit the following responses: dose-dependent estrogenic effects on the reproductive system, initiated vaginal cornification, increased uterine weight with decreased follicle stimulating hormone (FSH) and luteinizing hormone (LH) serum levels in ovariectomized rats [8], increased length of the follicular phase and total menstruation cycle [9], decreased estrogen, progesterone, FSH, and LH concentrations at the do...

“…Feeding PM powder suspended in water to ovariectomized rats induces proliferation of the vaginal epithelium and uterus endometrium and reduces the levels of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) [7,8]. Reduction of the levels of FSH and LH has also been observed in adult cyclic and aged menopausal female monkeys [9][10][11][12]. PM suppresses folliculogenesis and ovulation in adult cyclic female monkeys after a single or long-term feeding [9,10].…”

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confidence: 99%

“…Reduction of the levels of FSH and LH has also been observed in adult cyclic and aged menopausal female monkeys [9][10][11][12]. PM suppresses folliculogenesis and ovulation in adult cyclic female monkeys after a single or long-term feeding [9,10]. Intake of crude P. mirifica powder can relieve climacteric symptoms, such as hot flashes, frustration, sleep disorders and skin dryness in post-menopausal women [13].…”

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confidence: 99%

Assessment of Fertility and Reproductive Toxicity in Adult Female Mice after Long-Term Exposure to Pueraria mirifica Herb

Jaroenporn

Malaivijitnond

Wattanasirmkit

et al. 2007

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Abstract. The present study investigated the effects of long-term administration of Pueraria mirifica (PM) at non-toxic doses on the ovarian function and fertility of adult female mice based on evaluation of hematological and biochemical parameters [1]. Female mice were divided into 4 groups (36 mice/ group). Groups 1-3 were orally treated with a dose of 0 (PM-0), 10 (PM-10) or 100 mg/kg BW/day PM (PM-100), and group 4 was subcutaneously injected with 200 µg/kg BW/day of synthetic estrogen diethylstilbestrol (DES). The treatment schedule was separated into treatment and post-treatment periods. The duration of each period was 8 weeks. The PM-10 mice exhibited regular estrous cycles, while the PM-100 and DES treatments induced prolonged estrous cycles. Although no changes were observed in the uterus and ovary weights of the mice after the PM-100 and DES treatments, hyperplasia of the uterine endothelium and a decrease in the number of growing ovarian follicles were detected. The changes in the ovarian histologies of the PM-100 and DES mice were related to reductions in the levels of LH and FSH, which subsequently caused a decrease in mating efficiency. Once the PM mice were able to copulate, they were capable of successfully becoming pregnant and mothering offspring. No abnormalities were observed in the external morphologies and reproductive organ weights of the 50-day-old offspring. In conclusion, our results suggest that long-term exposure to 100 mg/kg BW of PM has adverse effects on the mating efficiency and reproduction of adult female mice and that administration of 10 mg/kg BW of PM does not induce any changes in the hypothalamic-pituitary-ovarian-uterine axis.