Assessment of Urinary Gonadotropin and Steroid Hormone Profiles of Female Cynomolgus Monkeys after Treatment with Pueraria mirifica

Journal of Reproduction and Development

Traisup

Picha³

2008

Self Cite

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...

Section: Cell Culturementioning

confidence: 99%

mentioning

confidence: 99%

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

Journal of Reproduction and Development

Traisup

Picha³

2008

Self Cite

“…Consumption of the tuberous powder generates a strong estrogenic activity as revealed by the induction of vaginal cornification in ovariectomized rats (5,6) and by the MCF-7 cell proliferation assay (7). Treatment of gonadectomized rats with plant tuber powder resulted in a reduction of LH and FSH levels (8), with dose-dependent estrogenic responses in female mice (9), female monkeys (10), and menopausal monkeys (11)(12)(13). The plant tuber powder also elicits dose-dependent physiological responses in male mice with a reduction in the weight of the epididymis and the seminal vesicles and reduced sperm motility and viability (14), promoting protection against osteoporosis in orchidectomized male (15) and female rats (16).…”

Section: Introductionmentioning

confidence: 99%

The mutagenic and antimutagenic effects of the traditional phytoestrogen-rich herbs, Pueraria mirifica and Pueraria lobata

Sutjit

Pulcharoen

et al. 2009

Braz J Med Biol Res

Pueraria mirifica is a Thai phytoestrogen-rich herb traditionally used for the treatment of menopausal symptoms. Pueraria lobata is also a phytoestrogen-rich herb traditionally used in Japan, Korea and China for the treatment of hypertension and alcoholism. We evaluated the mutagenic and antimutagenic activity of the two plant extracts using the Ames test preincubation method plus or minus the rat liver mixture S9 for metabolic activation using Salmonella typhimurium strains TA98 and TA100 as indicator strains. The cytotoxicity of the two extracts to the two S. typhimurium indicators was evaluated before the mutagenic and antimutagenic tests. Both extracts at a final concentration of 2.5, 5, 10, or 20 mg/plate exhibited only mild cytotoxic effects. The plant extracts at the concentrations of 2.5, 5 and 10 mg/plate in the presence and absence of the S9 mixture were negative in the mutagenic Ames test. In contrast, both extracts were positive in the antimutagenic Ames test towards either one or both of the tested mutagens 2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide and benzo(a)pyrene. The absence of mutagenic and the presence of anti-mutagenic activities of the two plant extracts were confirmed in rec-assays and further supported by a micronucleus test where both plant extracts at doses up to 300 mg/kg body weight (equivalent to 16 g/kg body weight plant tuberous powder) failed to exhibit significant micronucleus formation in rats. The tests confirmed the non-mutagenic but reasonably antimutagenic activities of the two plant extracts, supporting their current use as safe dietary supplements and cosmetics.

“…10) Phytoestrogens from the same plant cultivar exhibited a dose-dependent estrogenic effect on the reproductive system of ovariectomized rats, 11) cyclic female monkeys, 12) and aged menopausal monkeys. 13,14) In a study with male rats, the consumption of a high amount of the same plant cultivar caused disruption to male sex organs, including the epididymis and seminal vesicle, as well as to sperm motility and viability, 15) although it provided protection against osteoporosis in orchidectomized male rats.…”

mentioning

confidence: 99%

Major Isoflavonoid Contents of the 1-Year-Cultivated Phytoestrogen-Rich Herb,Pueraria mirifica

Bioscience, Biotechnology, and Biochemistry

2007

Self Cite

Pueraria mirifica is a tuberous plant enriched with active phytoestrogens. There is no established information about the factors influencing isoflavonoid storage in the tubers. We investigated the tuberous storage of the major isoflavonoids of 1-year-old plants. Four cultivars of P. mirifica were cultivated in the same field trial during the same period to establish a unique plant age and differentiation under the same environment and soil conditions. The tubers collected from the 1-year-old plants in the summer, rainy season and winter were submitted to an HPLC analysis with a gradient system comprising 0.1% acetic acid and acetonitrile. Five major isoflavonoids, puerarin, daidzin, genistin, daidzein and genistein, were adopted as standards. P. mirifica tubers of different cultivars collected in the same season exhibited significant differences in individual and total isoflavonoid contents, showing chemovariety. P. mirifica tubers of the same cultivar collected from different seasons also exhibited significant differences in individual and total isoflavonoid contents, showing the influence of season. In conclusion, the tuberous storage of major isoflavonoids in 1-yearcultivated plants was greatly diverse and was strongly influenced by the season and plant genetics.