Purifica mirifica mtf

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Try out PMC Labs and tell us what you think. Learn More. Pueraria mirifica PM , a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats.

Firstly, PM administered to ovariectomized animals at doses of 0. In a third experiment, postpubertal administration of 0. A ificant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0. Pueraria mirifica PM , also known as white Kwao Krua, is a plant found in northern and northeastern Thailand which belongs to the family of Leguminosae, and the soy, bean, and pea subfamily Papilionoideae.

ly, PM application for treatment of a range of conditions, including those related to the aging process, has been reported [ 1 ]. Dried and powdered tuberous roots of PM contain at least 17 chemical compounds with estrogenic biological activities, usually divided into three groups: the first group includes teniso flavonoids such as genistin, genistein, daidzein, daidzin, kwakhurin, kwakhurin hydrate, tuberosin, puerarin, mirificin, and puemiricarpene [ 2 , 3 ]; the second group of coumestans comprises coumestrol, mirificoumestan, mirificoumestan glycol, and mirificoumestan hydrate; and the third features chromenes, such as miroestrol, deoxymiroestrol, and isomiroestrol [ 2 ].

Miroestrol, the phytoestrogen with the highest estrogenic activity among all those isolated from PM, is considered similar to estriol, which is considered the safest estrogen for humans [ 4 , 5 , 6 , 7 ]. Puerarin might for about half of the total isoflavone content of PM, with lower amounts of genistin and daidzin present, all these being glycoside forms which can be partially hydrolyzed in the intestine by C-glycosyl bond cleavage to give the respective aglycoside forms: genistein, daidzein, and daidzein [ 2 ].

Nowadays, PM is available in tablets, extracts, creams, sprays, and powdered forms, so that it can be added to other medicinal preparations or herbs, and individual conditions require different applications and dosages [ 1 ]. It can be readily obtained from internet resources in many countries, including the USA and Japan, and is primarily used for supporting memory, smoothing the skin, increasing hair growth, improving appetite, and providing relief for ailments like osteoporosis and even cancer [ 9 , 10 , 11 , 12 ].

However, the effect of long-term administration at different doses has not yet been clarified in detail. Until now, no serious side effects have been recorded with the prescribed safe dosage, although at high doses PM may cause epilepsy, diabetes, asthma, and migraine [ 3 ]. Despite the data on the benefits of PM, there are reasons for concern that a herb which exhibits strong estrogen-like properties may stimulate the growth of existing estrogen-sensitive breast or endometrial tumors, pointing out questions such as: what is a safe dose? Recently, we further demonstrated that postpubertal administration of soy isoflavones at estrogenic doses promotes mammary and endometrial carcinogenesis in Donryu rats [ 15 ].

These data call into question the safety of long-term exposure to phytoestrogens with regard to effects on the mammary gland and endometrium. It is of particular importance that concentrations of PM which might exert promoting effects on mammary gland and uterine carcinogenesis be determined. Therefore, the present study was carried out to investigate the modifying effects of various doses of PM on mammary and uterine endometrial carcinogenesis using the Donryu rat model.

After ovariectomy, PM treatment at doses of 0. Animals were given PM at doses of 0 C , D , 0. Vaginal smears were obtained daily before and after starting the treatment, dried and stained with an aqueous solution of methylene blue. In the ovariectomized rats the absence of cyclicity was confirmed by castration smears typical of diestrus. Note that 0. The 0. Mean relative uterus weights were ificantly elevated in 0. Thus, weak, medium, and strong estrogenic activities of PM at doses of 0.

In this experiment, ificant decreases of body weights were observed in the 0. Thus, the test doses of PM in experiment 3 were set as: low, 0. Bromodeoxyuridine BrdU immunohistochemistry revealed a dose-dependent increase of cell proliferation in the terminal end buds of mammary glands of PM-treated rats after 4 weeks of administration Figure 2. Note the dose-dependent induction of cell proliferation by the short-term application of PM as compared to the DMBA initiation control rats.

Rat body weight curves are presented in Figure 3 A. Body weights of 0. No variation in food intake was observed among groups but decreased water consumption was noted in PM- and IA-treated animals. Body weight A and survival B curves of female Donryu rats in experiment 3; incidences of mammary adenocarcinomas C , benign tumors D , and volumes of mammary adenocarcinomas E and benign tumors F. Note the ificant decreases of body weights in the 0. Trends for decrease in survival were found for 0. ificant increases of mammary adenocarcinoma incidence were observed in 0.

Adenocarcinomas in PM- and IA-treated rats appeared earlier, and their volumes were higher than in the initiation control group. Development of benign tumors in the initiation control group starting at week 32 was evident. Mammary tumors were larger in animals with higher body weights. ificant increases of relative uterus weight were found with 0. Relative liver weights were ificantly decreased in 0. In addition, ificant increase of relative thymus weights at 0. Changes in rat survival are shown in Figure 3 B. Four animals in the initiation control, 6 rats in the 0. One rat each in the vehicle control, 0.

In contrast, causes of death in the 0. Two rats in the 0. The first rat was found dead at week 9, from the 0. Subsequently, one rat in the 0. The s of animals in the 0. Survival rates of 0. Data for changes in mammary gland adenocarcinoma and benign tumor incidences, multiplicities, and volumes—with representative pictures—are shown in Figure 3 C—F, Figure 4 A c,d and Table 1.

A Histopathological changes observed in mammary glands a — d and uteri e — l of initiation control, PM-, and IA-administered rats in experiment 3 hematoxylin and eosin. Moderate atypical hyperplasia featuring an increased of glands under the lining epithelium e , f. Well-differentiated endometrial adenocarcinoma AdCa g , h. Atypical glands present in the endometrium proliferating irregularly and invading the muscle layer arrows. Incidence and multiplicity of neoplastic lesions in the mammary glands and uteri of Donryu rats. Macroscopically measured mammary adenocarcinoma volumes were elevated in the 0.

Unexpectedly, sudden development of benign tumors in the mammary glands of the initiation control rats was observed at weeks 32— Animals with higher body weights had larger mammary tumors Figure 3 F. Data from histopathological examination of rat uteri are shown in Table 1 and Figure 4 A e—l ,B a—l.

At termination, the uteri of 0. In addition, stromal and adenomatous polyps were apparent Figure 4 A i—l. A ificant increase in the multiplicity of total atypical hyperplasias HPLs mild, medium, and severe was found in 0. Furthermore, ificant elevation of multiplicity of mild atypical HPLs was detected in the uteri of 0.

In addition, multiplicities of stromal and adenomatous polyps tended to increase with the 0. The of hematological and biochemical examinations of the blood are presented in Supplementary Materials Table S2. Furthermore, PM administration after the initiation of mammary and uterine carcinogenesis ificantly and dose-dependently suppressed the platelet counts.

Mammary adenocarcinomas metastasizing to the lungs were found in 0. In this study, the modifying effects of 0. In the medium and especially in the high dose PM groups, decreases of rat body weights, adipose deposition, and total cholesterol and triglyceride levels in the blood were obvious, likely due to antilipogenic effects of estrogenic compounds described ly, or perhaps to the decrease of water intake of rats given PM [ 16 ]. In the long-term experiment, we observed ificant increase of mammary adenocarcinoma development induced by PM at a dose of 0.

Interestingly, short- and long-term administration of PM applied at medium and high doses resulted in increase of uterus weight, and dilatation, hemorrhage, and inflammation of the uterine wall. However, the influence of PM on lesion development in the uterus was much less pronounced as compared to that in the mammary gland—and only atypical hyperplasia was elevated—at 0. However, the effects of biological substances possessing estrogenic activity generally appear to be dependent on the dose. However, in the case of PM, there are almost no data concerning the concentration of ingredients in the blood and tissues.

Recovery after cessation of treatment was dependent on the dosage of PM. Long-term PM administration at a dose of 0. It is important to further mention that the timing of exposure to substances with estrogenic bioactivities is thought to be critical for effects on breast cancer risk. Thus, prepubertal and postpubertal exposure to estrogenic compounds such as genistein could have different effects on cell proliferation in the terminal ductules of mammary glands [ 29 ]. In the present case, postpubertal exposure to PM, isoflavones or other test compounds with estrogenic activity induced cell proliferation and promoted mammary and uterine carcinogenesis in our two-step carcinogenesis model with DMBA and ENNG initiation.

Furthermore, PM elevated cell proliferation in the mammary glands of DMBA-initiated rats, which might lead to the promotion and progression of mammary tumors to greater malignancy. In addition, it inhibited the levels of calcium in the blood, and induced inflammation, hemorrhage, and dilatation of the uterine wall in rats.

Other chemicals were from Sigma Chemical Co. The Pueraria mirifica powder Lot No. The taxonomic and content identification was performed by the Seiko Yakuhin Kogyo K. The sample contained miroestrol 5. In the present experiment, test powder diets were prepared as follows: 0.

The accuracy of dose formulation and uniformity of blending of the diets was confirmed by the analytical chemistry laboratories at Oriental Yeast Co. NIHPLD diet constituents were carbohydrate, crude protein, crude fiber, fat, neutral detergent fiber, ash, fatty acids, amino acids, vitamins, and trace elements with no phytoestrogens.

All animals were checked once daily for general behavior and s of toxicity or a moribund state. Body weights, water and food intakes were measured every week for the first 12 weeks, and thereafter every 4 weeks. During the experiment, the specific s used to determine when the animals should be euthanized included no response to stimuli or a comatose condition, changes in heart rate and physical appearance, dyspnea or severe breathing problems, hypothermia, prostration, body weight loss, and changes in food and water intakes.

If ificant body weight loss or the water and food consumption changes were detected, the relevant animals were checked more precisely for other s of sickness. At euthanization, a systemic macroscopic pathological examination of liver, kidneys, spleen, adrenals, thymus, mammary glands, and uterus was performed. We performed ovariectomies on 25 female Donryu rats 5 weeks of age with normal estrous cycles. All animals were checked by vaginal cytology to confirm the absence of estrous cycles. Two weeks after the ovariectomy, for 2 weeks the rats were given 1 PM at doses of 0.

Vaginal smears stained with aqueous solution of methylene blue were used to check the estrogenic activity of the test compounds. Animal body weights were measured once a week, and general condition was examined once a day. The weights of uteri were measured at final necropsy to determine estrogenic effects of test compounds. Mammary gland, uterus, liver, kidneys, spleen, adrenals, and thymus were subjected to histopathological analysis.

Donryu rats with a mean body weight of g consumed PM in 15 g diet at doses of 20 0. PM at doses of 0. One hundred and seventeen 5-week-old female Donryu rats were divided into seven groups. It is known that soon after weaning, about postnatal day 35, pubertal development of Donryu rats starts. Since the onset of puberty is defined as the age in days at which vaginal opening occurs, rats were inspected daily for this purpose.

PM was administered to rats at doses of 0. Rats in the vehicle control group received the basal diet. One of the characteristics of Donryu rats is age-related persistent estrus followed by anovulation starting at the age of 5 months, the incidence of which rises until 8 months [ 32 ].

Malignant tumors usually metastasized to the lung, contained abscesses and ulcers, and were of dark color. Histopathologic analysis was performed according to the ly published classification of mammary tumors [ 33 ]. Twelve specimens were obtained from each uterus in cross-section and proliferative endometrial lesions were classified using the reported ly [ 34 ] into three degrees mild, moderate, and severe of atypical hyperplasia, stromal and adenomatous polyps, and adenocarcinoma.

In short-term experiment 2, for evaluation of cellular proliferation, BrdU staining was performed for rat mammary glands by the avidin-biotin-peroxidase complex ABC method reported ly [ 35 ]. A negative control was also included with the staining procedure by omitting the primary antibody. Blood samples were collected directly from the hearts of all surviving rats at the end of the study after overnight fasting. An automated hematology analyzer Sysmex XE, Mitsubishi Chemical Visuals, Osaka, Japan and an automatic analyzer Olympus AJ, Tokyo, Japan were employed for hematological and biochemical analyses of blood serum as ly described [ 36 ].

Purifica mirifica mtf

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Pueraria mirifica