• Clinical and Experimental Reproductive Medicine
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• v.40 no.2
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• pp.60-66
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• 2013

Objective: Impairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment. Although estrogen treatment stimulates spermatogenic recovery from the impaired spermatogenesis by suppressing the intra-testicular testosterone (ITT) level, side effects of estrogen are still major impediments to its clinical application in humans. Soybeans are rich in genistein, which is a phytoestrogen that binds to estrogen receptors and has an estrogenic effect. We investigated the effects of genistein administration on ITT levels, testis weight, and recovery of spermatogenesis in rats treated with a chemotherapeutic agent, busulfan. Methods: Busulfan was administered intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously into the back, or genistein was administered orally. Results: The weight of the testes was significantly reduced by the treatment with busulfan. The testis weight was partially restored after busulfan treatment by additional treatment with either the GnRH agonist or genistein. Busulfan also induced atrophy of a high percentage of the seminiferous tubules, but this percentage was decreased by additional treatment with either the GnRH agonist or genistein. Treatment with genistein was effective at suppressing and maintaining ITT levels comparable to that in the GnRH agonist group. Conclusion: Genistein effectively suppressed ITT levels and stimulated the recovery of spermatogenesis in rats treated with a chemotherapeutic drug. This suggests that genistein may be a substitute for estrogens, for helping humans to recover fertility after cancer therapy without the risk of side effects.

• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.4
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• pp.54-72
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• 2018

Objectives: The aim of this review is to investigate studies on Estrogen-like activity and to contribute to the utilization of herbal medicines including phytoestrogens. Methods: Electric searches were performed with Pubmed from 2013 to June 2018, for the words, 'herb and estrogen', 'traditional Chinese medicine and estrogen', 'Oriental medicine and estrogen', and 'Korean medicine and estrogen'. 49 papers are investigated and classified into 'in vitro', 'in vivo' and 'in vivo and in vitro' experimental studies. Results: 1. In vitro experimental studies have shown that estrogen-like effects of the components extracted from Rhei Radix et Rhizoma, Rubi Fructus, Sparganii Rhizoma, Epimedii Herba, Spatholobi Caulis, Evodiae fructus, Curcumae longae Radix, Ginseng Radix, Bupleuri Radix, Astragali Radix, Salviae Miltiorrhizae Radix, Puerariae Radix, Scutellariae Radix are present. 2. In vivo experimental studies have shown that estrogen-like effects of the components extracted from Phytolaccae Radix, Ligustri Lucidi Fructus, Alismatis Rhizoma, Notoginseng Radix, Puerariae Radix, Ginseng Radix, Cyperi Rhizoma, Cistanchis Herba, Cynomorii Herba, Granati fructus, Astragali Radix, Rehmanniae Radix Crudus, Epimedii Herba, Polygalae Radix, Artemisiae Annuae Herba are present. 3. In vitro and in vivo experimental studies have shown that estrogen-like effects of the components extracted from Cirsii Herba, Dioscoreae Rhizoma, Salviae Miltiorrhizae Radix, Cynomorii Herba, Cinnamomi cortex, Drynariae Rhizoma, Psoraleae Semen, Schisandrae Fructus, Epimedii Herba, Astragali Radix are present. Conclusions: Future studies will require additional research on numerous herbal medicines used in clinical practice.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.354-362
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• 2006

Dietary flavonoids have attracted a great deal of attention as agents for preventing estrogen-related diseases, such as postmenopausal symptoms, and for reducing the risk of estrogen-dependent cancer. Kaempferol is one of the most commonly found dietary phytoestrogen. The aim of this study was to investigate the estrogenic and/or antiestrogenic effect of kaempferol, which can confirm its potency as a preventive agent against estrogen-related diseases. Kaempferol has both estrogenic and antiestrogenic activity, which are biphasic response on estrogen receptor. The estrogenic activity of kaempferol induced via ER-mediated pathway depending on $E_2$ concentration $(\leq\;10^{-12}M)$. Kaempferol $(10^{-5}\;M)$ also caused antiproliferative effect on MCF-7 cell in the presence of $E_2\;(10^{-11}\;M)$ and restored to the addition of excess $E_2\;(10^{-7}\;M)$, which confirms that antiproliferation of kaempferol was induced via ER-dependent pathway. However, at $10^{-4}\;M$, concentration higher than the concentrations at which the estrogenic effects of kaempferol are detected $(10^{-5}\;M)$, kaempferol induced strong antiproliferative effect, but were unaffected by the addition of excess $E_2\;(10^{-7}\;M)$ indicating that kaempferol exerts antiproliferation via ER-independent pathway. In particular, kaempferol blocked the focus formation induced by $E_2$, which confirms that kaempferol might inhibit the malignant transformation caused by estrogens. Therefore, we suggested that kaempferol might regulate a suitable level of estrogenic activity in the body and is expected to have potential beneficial effects in preventing estrogen imbalance diseases (breast cancer, osteoporosis, cardiovascular disease and etc.).

• Journal of Life Science
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• v.13 no.6
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• pp.799-804
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• 2003

In order to verify the occurrence of an estrogenic compound in natural products, the estrogenic activity was measured using an in vitro detection system. For this system, human breast cancer cell line MCF7 was transfected using an estrogen responsive CAT reporter plasmid. Estrogenic activities of photosynthetic algae spirulina and sea lettuce were evaluated using this system. Estrogenic activities of a $500\mug/ml\; and\; 50 \mug/ml$ ethanol extracts of spirulina were as much as that of $10^{-8}$M standard solution (17$\beta$-estradiol) and activity of $5\mug/ml$ ethanol extract of spirulina was as much as that of $10^{-10}$ M standard solution. However, no significant estrogenic activity was observed using sea lettuce extract. Estrogenic activities of marine animals, such as star fish and shrimp, were also evaluated using this system, however, no significant estrogenic activity was observed in these extracts. In this result, it is confirmed that spirulina extract possesses estrogenic compound.

• Food Science and Biotechnology
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• v.15 no.3
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• pp.392-398
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• 2006

Four flavonoids 1-4 and one phytosterol 5 were isolated from methanol extract of Taekwangkong, one of the soybean cultivars, and the structures of these compounds were fully characterized by physical and spectral analysis. The content of compounds 1-4 as determined by $C_{18}$ reversed phase HPLC (high-performance liquid chromatography) coupled with diode-array detector were 12.1, 624.6, 18.0, and $219.6\;{\mu}g/g$, respectively, and the total phenolic content of this cultivar was measured as 3.7 mg gallic acid equivalent per g dry material (GAB/g). Also, compound 1 showed strong radical scavenging activity in the 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assay ($IC_{50}\;=\;47.6\;{\mu}M$), five-fold higher than seen in the 1,1-diphenyl-2-picrylliydrazyl (DPPH) assay. These results lead to the conclusion that soybean not only has many phytoestrogens but also has potent antioxidant activity.

• Archives of Pharmacal Research
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• v.29 no.7
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• pp.570-576
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• 2006

Phytoestrogen biochanin A is an isoflavone derivative isolated from red clover Trifolium pratense with anticarcinogenic properties. This study examined the action of biochanin A with the carcinogen activation pathway that is mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 breast carcinoma cells. Treating the cells with biochanin A alone caused the accumulation of CYP1A1 mRNA and an increase in CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity in a dose dependent manner. A concomitant treatment with 7,12-dimethylbenz[a]anthracene (DMBA) and biochanin A markedly reduced the DMBA-inducible EROD activity and CYP1A1 mRNA level. In addition, the biochanin A treatment alone activated the DNA-binding capacity of the AhR for the dioxin-response element (DRE) of CYP1A1, as measured by the electrophoretic-mobility shift assay (EMSA). EMSA revealed that biochanin A reduced the level of the DMBA-inducible AhR-DRE binding complex. Furthermore, biochanin A competed with the prototypical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), for binding to the AhR in an isolated rat cytosol. The biochanin A competitively inhibited the metabolic activation of DMBA, as measured by the formation of the DMBA-DNA adducts. These results suggest that biochanin A may thus be a natural ligand to bind on AhR. Therefore, biochanin A may be due to act an antagonist/agonist of the AhR pathway.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.3
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• pp.236-244
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• 2021

Objective: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, irregular menstruation, ovulatory dysfunction, and insulin resistance. Recent studies have reported the possible role of phytoestrogens in PCOS. This animal study aimed to evaluate the effects of genistein on insulin resistance, inflammatory factors, lipid profile, and histopathologic indices on PCOS. Methods: PCOS was induced by 1 mg/kg of letrozole in adult Sprague-Dawley rats. The rats then received normal saline (PCOS group), 150 mg/kg of metformin, or 20 mg/kg of genistein dissolved in 1% methylcellulose solution for 42 days. Body weight, the glycemic and lipid profile, and inflammatory, antioxidative, and histopathological parameters were assessed at the end of the intervention. Results: Treatment with genistein significantly alleviated the increased level of fasting blood insulin (p=0.16) and the homeostatic model assessment of insulin resistance (p=0.012). In addition, the genistein group had significantly lower levels of serum malondialdehyde (p=0.039) and tumor necrosis factor-alpha (p=0.003), and higher superoxide dismutase enzyme activity (p<0.001). Furthermore, the histopathological analysis indicated that genistein administration led to an increase in luteinization and the development of fewer cysts (p<0.05). Conclusion: Biochemical and histopathological analyses indicated that genistein administration to rats with PCOS induced significant remission in oxidative, inflammatory, and glycemic and histopathologic parameters.

• Natural Product Sciences
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• v.25 no.3
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• pp.208-214
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• 2019

Trigonella foenum-graceum L. (fenugreek) is a phytoestrogen, a nonsteroidal organic chemical compound from plants which has similar mechanism of action to sex hormone estradiol-$17{\beta}$. This study aims to assess the effectivity of fenugreek seeds extract on collagen type I alpha 1 (COL1A1) and collagen type III alpha 1 (COL3A1) which are both decreased in aging skin and become worsen after menopause. This in vitro experimental study used old human dermal fibroblast from leftover tissue of blepharoplasty on a postmenopausal woman (old HDF). As a control of the fenugreek's ability to trigger collagen production, we used fibroblast from preputium (young HDF). Subsequent to fibroblast isolation and culture, toxicity test was conducted on both old and young HDF by measuring cell viability on fenugreek extract with the concentration of 5 mg/mL to $1.2{\mu}g/mL$ which will be tested on both HDF to examine COL1A1 and COL3A1 using ELISA, compared to no treatment and 5 nM estradiol. Old HDF showed a 4 times slower proliferation compared to young HDF (p<0.05). Toxicity test revealed fenugreek concentration of $0.5-2{\mu}g/mL$ was non-toxic to both old and young HDF. The most significant fenugreek concentration to increase COL1A1 and COL3A1 secretion was $2{\mu}g/mL$ (p<0.05).

• Journal of Ginseng Research
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• v.46 no.4
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• pp.526-535
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• 2022

Background: During the pathogenesis of tendinopathy, the chronic inflammation caused by the injury and apoptosis leads to the generation of scars. Ginsenoside Rg1 (Rg1) is extracted from ginseng and has anti-inflammatory effects. Rg1 is a unique phytoestrogen that can activate the estrogen response element. This research aimed to explore whether Rg1 can function in the process of tendon repair through the estrogen receptor. Methods: In this research, the effects of Rg1 were evaluated in tenocytes and in a rat model of Achilles tendinitis (AT). Protein levels were shown by western blotting. qRT-PCR was employed for evaluating mRNA levels. Cell proliferation was evaluated through EdU assay and cell migration was evaluated by transwell assay and scratch test assay. Results: Rg1 up-regulated the expression of matrix-related factors and function of tendon in AT rat model. Rg1 reduced early inflammatory response and apoptosis in the tendon tissue of AT rat model. Rg1 promoted tenocyte migration and proliferation. The effects of Rg1 on tenocytes were inhibited by ICI182780. Rg1 activates the insulin-like growth factor-I receptor (IGF1R) and MAPK signaling pathway. Conclusion: Rg1 promotes injured tendon healing in AT rat model through IGF1R and MAPK signaling pathway activation.

• Development and Reproduction
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• v.10 no.4
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• pp.255-261
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• 2006

Although some phytoes rogens might have beneficiary rather than adverse effects, most endocrine disrupting compounds(EDCs) are considered to be harmful to human and wildlife health through interfering the endocrine system. Previously we found that prepubertal exposure to genistein(GS), a well-known isoflavone phytoestrogen, could activate the reproductive system of immature female rats resulting precocious puberty. Interestingly, di(2-ethyl hexyl) phthalate(DEHP) exposure brought inverse result, a delayed puberty, in the same experimental regimen. In this study, we examined whether prepubertal exposure to GS or DEHP affect the gene expressions of estrogen receptors($ER\;{\alpha}$ and $ER\;{\beta}$) and LH receptor(LHR) which represent the maturational status of ovary and uterus in immature rats. GS (100 mg/kg/day) was administered daily from postnatal day 25 to the day when the first vaginal opening(VO) was observed, and the animals were sacrificed on the next day(day 32). Similarly, DEHP(l00 mg/kg/day) was administered daily from postnatal day 25 through the day when the first V.O. in control group was observed, and the animals were sacrificed on the next day(day 36). To determine the transcriptional changes in the hormone receptors, total RNAs were extracted from ovary and uterus and were applied to semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). In the GS group, the transcriptional activities of $ER\;{\alpha}$, $ER\;{\beta}$ and LHR in uterus and LHR in ovary were significantly increased when compared to those of control group. In the DEHP group, the transcriptional activities of all the hormone receptors measured were significantly lowered when compared to those of control group. These alteration of the reproductive hormone receptor expressions in ovary and uterus might be represent the phenotypic aspects(secondary sexual characteristics) such as tissue weights and reproductive hormone levels during perinatal period in immature female rats.