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In vitro Stimulation of Granulosa Cells by a Combination of Different Active Ingredients of Unkei-to

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Abstract

Unkei-to is widely used in traditional Japanese herbal medicine for its ovulation-inducing effect. In the present study, we investigated the in vivo effects of unkei-to and its compounds on the steroidogenesis and cytokine secretion in human granulosa cells. Unkei-to stimulated the secretions of 17beta-estradiol and progesterone from highly luteinized granulosa cells obtained from in vitro fertilization patients; the stimulated effect on estradiol secretion occurred with 0.3 microg/ml, while a significant effect on progesterone secretion was obtained at 10 microg/ml. The unkei-to stimulation of estradiol secretion could be accounted for by the effects of its ingredients, Shakuyaku (paeoniae radix, Paeonia lactiflora Pallas) and Keihi (cinnamomi cortex, Cinnamomum cassia Blume); while dose response curves for unkei-to and Keihi to induce progesterone production were superimposable. Exposure of the cells to unkei-to caused dose-dependent increases in the concentrations of interleukin (IL)-1beta, IL-6 and IL-8 in the culture medium. Similar results were obtained when cells were incubated with the ingredient Ninjin (ginseng radix, Panax ginseng C.A. Meyer), but not Shakuyaku and Keihi. These results indicate that unkei-to has direct stimulatory effects on human granulosa cells to stimulate the steroidogenesis and secretion of cytokines (IL-1, IL-6 and IL-8). The various beneficial actions of unkei-to on the ovary may result from a combination of different ingredient herbs with different stimulatory effects on both steroidogenesis and the ovulatory process within the ovary, as well as stimulatory effect on the hypothalamus-pituitary axis.

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... Theoretically, concurrent use with other drugs that affect GABA (gamma-amino butyric acid) may have additive effects. • Estrogens: Cinnamomi cortex as a component of the unkei-to combination product stimulated estradiol secretion in laboratory study [472]. Theoretically, concurrent use of cinnamon with estrogens may have additive effects. ...
... Theoretically, concurrent use with other herbs or supplements that affect GABA may have additive effects. • Phytoestrogens: Cinnamomi cortex as a component of the unkei-to combination product stimulated estradiol secretion in laboratory study [472]. Theoretically, concurrent use of cinnamon with estrogens may have additive effects. ...
... Cinnamic aldehyde inhibited AA release and thromboxane B2 formation, which may contribute to reduced platelet aggregation [480]. • Estrogens: Cinnamomi cortex as a component of the unkei-to combination product stimulated estradiol secretion in laboratory study [472]. • Heart rate: In animal study, various cinnamon species [77,466,473,543,553], including C. migao [471], decreased the heart rate. ...
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An evidence-based systematic review of cinnamon (Cinnamomum spp.), including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing, by the Natural Standard Research Collaboration is discussed in this monograph.
... Our search identified 33 laboratory (pre-clinical) studies ( Figure 1). Eighteen studies met the inclusion criteria, nine reported on receptor binding assays or ovarian or pituitary (brain) cell cultures, [36][37][38][39][40][41][42][43][44] and nine used an animal experimental model with hormone assays and/or post-mortem examination of ovarian, uterine and brain histology, [45][46][47][48][49][50][51][52][53] ( Table 1). We excluded 15 studies for the following reasons; investigation of effects in male animals (n = 4) and investigations which commenced with constituents that were isolated from herbal medicines (n = 5). ...
... Paeonia lactiflora and Cinnamomum cassia combination was investigated for steroid hormonal effects on cultured human granulosa cells (obtained from women undergoing IVF). Cells were incubated with different doses for 48 hours [42] One clinical trial investigated the effects of Paeonia lactiflora and Cinnamomum cassia combination (Unkei-to) [57]. This single arm study included amenorrheic women aged 17-29 years (n = 157) with a sub group of women with hyper-functioning oligo/amenorrhoea (n = 42). ...
... 1. Increased granulosa production of oestradiol [42]. ...
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Polycystic ovary syndrome (PCOS) is a prevalent, complex endocrine disorder characterised by polycystic ovaries, chronic anovulation and hyperandrogenism leading to symptoms of irregular menstrual cycles, hirsutism, acne and infertility. Evidence based medical management emphasises a multidisciplinary approach for PCOS, as conventional pharmaceutical treatment addresses single symptoms, may be contra-indicated, is often associated with side effects and not effective in some cases. In addition women with PCOS have expressed a strong desire for alternative treatments. This review examines the reproductive endocrine effects in PCOS for an alternative treatment, herbal medicine. The aim of this review was to identify consistent evidence from both pre-clinical and clinical research, to add to the evidence base for herbal medicine in PCOS (and associated oligo/amenorrhoea and hyperandrogenism) and to inform herbal selection in the provision clinical care for these common conditions. We undertook two searches of the scientific literature. The first search sought pre-clinical studies which explained the reproductive endocrine effects of whole herbal extracts in oligo/amenorrhoea, hyperandrogenism and PCOS. Herbal medicines from the first search informed key words for the second search. The second search sought clinical studies, which corroborated laboratory findings. Subjects included women with PCOS, menstrual irregularities and hyperandrogenism. A total of 33 studies were included in this review. Eighteen pre-clinical studies reported mechanisms of effect and fifteen clinical studies corroborated pre-clinical findings, including eight randomised controlled trials, and 762 women with menstrual irregularities, hyperandrogenism and/or PCOS. Interventions included herbal extracts of Vitex agnus-castus, Cimicifuga racemosa, Tribulus terrestris, Glycyrrhiza spp., Paeonia lactiflora and Cinnamomum cassia. Endocrine outcomes included reduced luteinising hormone (LH), prolactin, fasting insulin and testosterone. There was evidence for the regulation of ovulation, improved metabolic hormone profile and improved fertility outcomes in PCOS. There was evidence for an equivalent effect of two herbal medicines and the pharmaceutical agents bromocriptine (and Vitex agnus-castus) and clomiphene citrate (and Cimicifuga racemosa). There was less robust evidence for the complementary combination of spirinolactone and Glycyrrhiza spp. for hyperandrogenism. Preclinical and clinical studies provide evidence that six herbal medicines may have beneficial effects for women with oligo/amenorrhea, hyperandrogenism and PCOS. However the quantity of pre-clinical data was limited, and the quality of clinical evidence was variable. Further pre-clinical studies are needed to explain the effects of herbal medicines not included in this review with current clinical evidence but an absence of pre-clinical data.
... GZT has been extensively used clinically for pyrexia, influenza, sore throat and inflammation. Recent studies showed that it affected the cellular signal transduction in the hypothalamus via the regulation of the level of prostaglandin E 2 (PGE 2 ), cyclooxygenase-2 (COX-2) and other enzymes in vitro (Guo et al., 2006; Sun et al., 2004) and reduced the amount of inflammatory factors induced by LPS and poly (I:C) (Zhao et al., 2006). 3-phenyl-propenal is one of the principle compounds in GZT. ...
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... Exposure of the cells to Unkei-to caused dosedependent increases in the concentrations of interleukin (IL)-1β, IL-6 and IL-8 in the culture medium. 38 These results indicate that Unkei-to has direct stimulatory effects on human granulosa cells to stimulate the steroidogenesis and the secretion of cytokines. The various beneficial actions of Unkei-to on the ovary might result from a combination of different herbal ingredients with stimulatory effects on both steroidogenesis and the ovulatory process within the ovary, as well as with stimulatory effects on the hypothalamuspitutary axis. ...
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... Effect observed due to its key ingredients like Paeoniae radix, Paeonia lactiflora, Cinnamomi cortex and Cinnamomum cassia. The various beneficial actions of unkei-to on the ovary may result from a combination of different ingredient herbs with different stimulatory effects on both steroidogenesis and the ovulatory process within the ovary, as well as stimulatory effect on the hypothalamus-pituitary axis [24][25] . ...
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Objectives : Ongyeong-tang (OGT) is a traditional herbal formula used to cure gynaecological disorders. OGT consists of 12 herbal medicines containing various bioactive components. Therefore, the development of suitable analytical method for the marker compounds is necessary for the quality control of OGT. Methods : Determination of the 18 marker compounds in OGT preparations was quantitatively performed by high-performance liquid chromatography-photodiode array detection analysis. The marker compounds were separated on a reversed-phase C 18 column and the analytical method was successfully validated, which was applied to compare OGT extracts from laboratory preparation and commercial OGT granules. Results : Limit of detection and limit of quantification values were in the ranges of 0.001-0.016?g/mL and 0.003-0.047?g/mL, respectively. Precision was 0.03-3.71 % within a day and 0.03-3.81 % over four consecutive days. Recovery of marker compounds ranged from 90.63-108.26 %, with relative standard deviation (RSD) values , with the RSD value
... Clinically, WJT has also been shown to cause a significant decrease in plasma luteinizing hormone (LH) levels in anovulatory patients with high plasma LH concentrations, including those with PCOS [46]. Furthermore, WJT improves the functioning of human granulosa cells in vitro by enhancing 17β-estradiol and progesterone secretion [47]. ...
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Polycystic ovary syndrome (PCOS) is a common condition, affecting 5–10% of women of reproductive age worldwide. It has serious reproductive implications and causes mood disorders and metabolic disorders, such as type-2 diabetes. Because PCOS reflects multiple abnormalities, there is no single drug that can treat all its symptoms. Existing pharmaceutical agents, such as oral contraceptives (OCs), are suggested as a first-line therapy for menstrual irregularities; however, OCs are not appropriate for women pursuing pregnancy. Additionally, insulin-sensitizing agents, which appear to decrease insulin levels and hyperandrogenemia in women with PCOS, have been associated with a high incidence of gastrointestinal adverse effects. It is a common practice in Chinese society to receive traditional Chinese medicine (TCM) for treatment of gynecological problems and infertility. Current research demonstrates that several herbs and herbal formulas show beneficial effects in PCOS treatment. In this study, we conducted the first large-scale survey through the Taiwan National Health Insurance Program database to analyze TCM utilization patterns among women with PCOS in Taiwan during 1997–2010. The survey results revealed that 89.22% women with newly diagnosed PCOS had received TCM therapy. Jia-Wei-Xiao-Yao-San and Xiang-Fu (Rhizoma Cyperi) were the most commonly used formula and single herb, respectively, in the database. In addition, we found that the top five commonly prescribed single herbs and herbal formulas have shown promise in treating symptoms associated with PCOS.
Article
Herbal medicines are widely used for centuries to treat illness and improve health in Asia and the use of these remedies has become a worldwide form of alternative therapy. However, there is very limited evidence from randomized controlled trials to support the efficacy of the vast majority of herbal products. Of the commonly used herbal medicines, systemic clinical experiences and promising experiments in animals have found potential evidence of efficacy for six herbal medicines (Unkei-to, Hachimijio-gan, Keishi-bukuryo-gan, Toki-shakuyaku-san, Shakuyaku-kanzo-to, Sairei-to) in the treatment for female reproductive dysfunction. Because herbs may contain potent bioactive substances, the physician should have an opportunity to outline more stringent regulation, similar to over-the counter drug.
Chapter
This chapter presents information on treatment of polycystic ovary syndrome (PCOS) by use of botanicals. PCOS in mentioned to be the most common endocrine disease in young women and the most common cause of anovulatory infertility. A table is presented that summarizes the potential benefits of botanicals in PCOS. The various disorders associated with PCOS are discussed which include anovulation, obesity, dyslipidemia and inflammation. The botanical treatment for ovarian disorders due to PCOS is given namely: N-acetyl cysteine (NAC) which is an antioxidant, d Chiro-inositol, chaste berry, etc. The treatments for insulin resistance in PCOS include cinnamon, gymnema, quercetin and white peony. Management of dyslipidemia in PCOS by use of botanicals consists of red rice yeast, curcumin and d Chiro-inositol. PCOS patients are mentioned to be at risk for cardiovascular diseases. The circulating C-reactive protein, interleukin-6 and tumor necrosis factor are the inflammatory markers for cardiovascular diseases and PCOS patients have higher inflammatory markers in the circulation. The use of fish or flax seed oils is mentioned to reduce inflammation in PCOS.
Article
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Chapter
Polycystic Ovary Syndrome [PCOS], a disorder of gynecological importance, is a common cause of infertility in women of reproductive ages. Women with PCOS have excess androgen levels or in other words, the production of androgen in females is highly elevated. Besides female infertility, PCOS is also associated with insulin resistance [IR], obesity, hypertension, hyperlipidemia and an increased risk for diabetes. The treatment options for PCOS are currently very limited offering only palliative care. As an alternative to overcome the limitations of the conventional therapeutic approaches, herbal medicine may be a future treatment option for the therapeutically challenging PCOS. Studies demonstrate that phytochemicals from various medicinal plants possess the ability to reduce the adverse effects occurring from the consumption of pharmaceutical drugs. There is evidence suggesting that the bioactive compounds found in plants which include flavonoids, polyphenols, phytoestrogen, polyunsaturated fatty acids [PUFAs] and other plant products show positive effects in attenuation of the syndrome. Here, we review the role of various herbal extracts and plant compounds in PCOS. Evidence suggests that phytocompounds increase ovulation, fertility as well as cause a decrease in insulin resistance and androgen excess. These phytocompounds may be effective in PCOS by affecting the hormone levels and ovarian weight.
Article
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Polycystic ovary syndrome (PCOS) is a complex heterogeneous disorder characterized by androgen excess and ovulatory dysfunction; it is now known to be closely linked to metabolic syndrome. Recent research suggests that insulin resistance plays an important role in the pathogenesis of PCOS which may lead to the excessive production of androgens by ovarian theca cells. Currently there is no single drug that can treat both the reproductive and metabolic complications of the disorder. Existing pharmaceutical agents such as hormonal therapies have been associated with side effects and are not appropriate for PCOS women with infertility. Additionally, insulin sensitizing agents useful for treating the metabolic abnormalities in PCOS have limited efficacy for treating reproductive aspects of the disorder. Chinese herbal medicines have a long history of treating gynaecological problems and infertility and therefore may be a novel approach to the treatment of PCOS. Current research demonstrates that the compounds isolated from herbs have shown beneficial effects for PCOS and when combined in an herbal formula can target both reproductive and metabolic defects simultaneously. Therefore, further investigation into Chinese herbal medicine in the treatment of PCOS is warranted.
Article
Chinesische Arzneidrogen wurden in der Chinesischen Medizin von früh an für Funktionsstörungen und Krankheiten des reproduktiven Systems eingesetzt. Daher verwundert es nicht, dass sich unter diesen viele mit hormonartigen Effekten finden lassen. Diese wurden von der westlichen TCM-Welt bisher so gut wie gar nicht zur Kenntnis genommen. Am meisten untersucht und nachgewiesen sind die Phytoöstrogeneffekte, dazu kommen progesteronartige, androgenartige, ihre jeweiligen antagonistischen Wirkungen sowie weitere. Bei den östrogenartig wirkenden Drogen stellt sich die Frage eines potenziellen Proliferationseffektes bei Mammakarzinomen, zumal viele von ihnen in vitro das Wachstum humaner Mammakarzinomzellen stimulieren. Soja und Sojaisoflavone können in dieser Hinsicht als sicher gelten, jedoch kann man diese Aussage nicht einfach auf andere Drogen mit Phytoöstrogencharakter extrapolieren. Vielmehr bedarf jede Arzneidroge einer gesonderten Betrachtung. Epidemiologische Studien zur Auswirkung einer chinesischen Arzneitherapie auf die Inzidenz oder — bei Einnahme nach Diagnosestellung — auf den Verlauf östrogenabhängiger Tumore liegen nur ganz vereinzelt vor. Diese sprechen nicht für eine erhöhte Inzidenz eines Mammakarzinoms, eines Endometriumkarzinoms oder den ungünstigen Verlauf eines Mammakarzinoms, sondern eher für das Gegenteil. Angesichts der In-vitro- und In-vivo-Ergebnisse und des nicht beweisenden Charakters epidemiologischer Studien ist der Einsatz der in Frage stehenden Arzneidrogen sehr sorgsam gegenüber den Risiken abzuwägen und im Zweifelsfall Zurückhaltung zu üben.
Chapter
One of the most common endocrine disorder in females during reproductive age which leads to infertility, metabolic derangements, and also psychological impairments is polycystic ovary syndrome (PCOS). This syndrome has been known to increases the risk of type 2 diabetes, obesity, hypertension, cardiovascular diseases, lipid disorders, and also autoimmune thyroiditis. Impending complication list includes malignancies like breast and endometrial cancer. The actual cause of this syndrome is unknown, and perhaps, it could be due to a combination of various unmodifiable genetic factors and modifiable environmental factors. Several research studies have been carried out on management of PCOS, and many medicinal plants have been used as an alternative therapy for oligo/amenorrhoea, hyperandrogenism, and PCOS in women. The chapter gives an insight on PCOS, its management, and elucidates the effects of medicinal plants on PCOS.
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We evaluated the effects of the traditional Chinese medicines, Hachimi-jio-gan, Juzen-taiho-to and Unkei-to, on bone loss in murine model of senile osteoporosis (SAMP6). Two-month-old SAMP6 were divided into control and experimental groups. The control mice had the tap water available as the only drinking fluid. The experimental mice were given 0.05% aqueous solution of Hachimi-jio-gan, Juzen-taiho-to or Unkei-to for three months. The solution intake of a mouse averaged 5 ml per day. The bones were studied morphologically and histomorphometrically, together with bone mineral density (BMD), serum parathyroid hormone (PTH) and estradiol levels. In the control group, BMD and the amount of bone forming surface were low, the serum PTH level was high when compared with the normal mice SAMR1. Many osteocytes and osteoblasts showed degenerative changes and numerous mast cells were observed in the bone marrow. Compared with controls, the serum estradiol level was higher in the Unkei-to group. However, we did not find any significant changes of bones. In the Hachimi-jio-gan and Juzen-taiho-to groups, the bone mass and the amount of bone forming surface increased. Most of the osteocytes and osteoblasts appeared normal. As compared with controls, the number of mast cells in bone marrow decreased in the Hachimi-jio-gan group. The serum PTH level had declined in the Juzen-taiho-to group. The present study provides certain evidence that Hachimi-jio-gan and Juzen-taiho-to are effective in preventing bone loss in SAMP6, while Unkei-to can only improve the ovary function.
Article
Fever, an elevation in body temperature, is thought to be terminally mediated by prostaglandin E(2) (PGE(2)). Both Guizhi Tang (GZT) and its active fraction A (Fr.A) showed an antipyretic effect in rats. 3-Phenyl-2-propene-1-ol was one of the active compounds isolated from Fr.A. In the present study, we examined the influence of interleukin-1beta (IL-1beta) on prostaglandin E(2) (PGE(2)) release, and the effect of 3-phenyl-2-propene-1-ol on IL-1beta-induced PGE(2) release from rat cerebral endothelial cells (rCMEC). Cultured rCMEC were used in the study. In vitro, cells express typical phenotypic markers of brain endothelium. Using a monoclonal antibody against von Willebrand factor, immunocytochemical analysis revealed positive immunoreactivity in the cytoplasm of cultured cells. rCMEC were incubated in M199 medium containing IL-1beta in the presence or absence of 3-phenyl-2-propene-1-ol. After incubation, the conditioned media were collected and the amount of PGE(2) was measured by enzyme-linked immunosorbent assay (ELISA). IL-1beta increased the production of PGE(2) in a dose- and time-dependent manner. 3-Phenyl-2-propene-1-ol significantly decreased IL-1beta-induced PGE(2) release in a dose-dependent manner. Our results indicate that 3-phenyl-2-propene-1-ol inhibits the PGE(2) release from rCMEC stimulated by IL-1beta, and may have an antipyretic effect.
Chapter
One of the most common endocrine disorder in females during reproductive age which leads to infertility, metabolic derangements, and also psychological impairments is polycystic ovary syndrome (PCOS). This syndrome has been known to increases the risk of type 2 diabetes, obesity, hypertension, cardiovascular diseases, lipid disorders, and also autoimmune thyroiditis. Impending complication list includes malignancies like breast and endometrial cancer. The actual cause of this syndrome is unknown, and perhaps, it could be due to a combination of various unmodifiable genetic factors and modifiable environmental factors. Several research studies have been carried out on management of PCOS, and many medicinal plants have been used as an alternative therapy for oligo/amenorrhoea, hyperandrogenism, and PCOS in women. The chapter gives an insight on PCOS, its management, and elucidates the effects of medicinal plants on PCOS.
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Freshly isolated granulosa cells obtained from women undergoing in-vitro fertilization (IVF) become refractory to further gonadotrophin stimulation in culture due to their previous hormonal treatment. However, when precultured for 7 days in gonadotrophin-free medium they regain their response to both human chorionic gonadotrophin (HCG) and follicle stimulating hormone (FSH) with a 10-fold and 5-fold increase in progesterone production respectively, within an additional 7 days of culture. Forskolin, a direct activator of adenylate cyclase, increased progesterone levels 12-fold compared with non-stimulated cultures. Oestradiol formation was also significantly elevated (P < 0.005) following 48 h stimulation with luteinizing hormone (LH), FSH or forskolin. Intracellular cAMP levels rose 1.5-fold, 10-fold and 15-fold after 1 h of FSH, HCG or forskolin treatment. Expression of both cytochrome P450 side chain cleavage enzyme (SCC) and the steroidogenic transcription factor SF1/Ad4BP could be demonstrated by Western blotting. However, elevation of P450 SCC alone was evident following FSH and HCG stimulation. In the presence of serum, the ultrastructure of these cultured cells displayed numerous lipid droplets and well-developed mitochondria, characteristic of highly steroidogenic cells. The proportion of apoptotic nuclei in these cultures was <30%. Removal of the serum increased apoptotic incidence to 40%, whereas addition of FSH prevented cell death significantly (P < 0.01). HCG and forskolin increased apoptosis to ∼50%, while treatment with 8Br-cAMP led to 80% cell death. Our data suggest that, after prolonged culture, human granulosa cells can regain cAMP and steroidogenic response to gonadotrophin stimulation. Moreover, our experiments indicate that apoptosis and steroidogenesis can coexist in the same cell population while the interrelationship between these processes can be determined by the intracellular levels of cAMP.
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A cytokine-induced neutrophil chemoattractant (CINC/gro), which belongs to the interleukin (IL)-8 family, acts as a functional chemoattractant for neutrophils in rats. In the present study, we examined whether CINC/gro contributes to the ovulation process in the rat ovulation system. In rat ovaries, CINC/gro was immunohistochemically recognized in the theca layer of the antral follicle but not in the granulosa cells. To clarify the role of CINC/gro in the ovulation process, CINC/gro protein and mRNA were examined during pregnant mare serum gonadotropin (PMSG)-hCG treatment. CINC/gro protein did not increase as a result of PMSG injection. However, it increased rapidly after hCG injection and peaked at 6 h after hCG. CINC/gro mRNA was also strongly expressed after hCG injection. The increase of CINC/gro protein followed increases in IL-1beta and tumor necrosis factor alpha (TNFalpha). In the whole ovarian dispersate culture, FSH, hCG, IL-1beta, and TNFalpha stimulated the production of CINC/gro protein in a dose-dependent manner. In particular, the stimulatory effects of IL-1beta and TNFalpha were stronger than those of gonadotropins. These results suggest that CINC/gro plays an important role in the rat ovulation process by attracting neutrophils. CINC/gro increased just prior to ovulation, and it may be regulated directly by cytokines such as IL-1beta and TNFalpha and indirectly by gonadotropins.
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To treat anovulatory women with high plasma LH levels with unkei-to. A total of 100 patients with polycystic ovary syndrome (n = 38) or non-polycystic ovary syndrome (n = 62) were allocated randomly into two groups. Endocrine levels (FSH, LH and estradiol), follicle growth and response to unkei-to were compared for 52 subjects in the unkei-to group and 48 subjects in the control group. Unkei-to induced significant decreases in plasma LH in polycystic ovary syndrome and non-polycystic ovary syndrome with high LH levels. Plasma estradiol levels increased significantly (43.5%) in eight weeks of treatment with unkei-to. Significant development of the dominant follicle was also observed in patients treated with unkei-to. When women suffering from ovulatory failure or irregular menstruation and having high plasma LH concentration were treated with unkei-to for eight weeks, a reduction in the serum LH level of at least 1 SD from baseline was noted in 45.5% of polycystic ovary syndrome patients and in 80.0% of non-polycystic ovary syndrome patients. The mean rate of reduction of serum LH was 22.2 +/- 35.7% in polycystic ovary syndrome patients and 49.7 +/- 15.3% in non-polycystic ovary syndrome patients. This reduction was significant in the non-polycystic ovary syndrome patients (P = .030). The rate of menstrual cycle improvement, including successful ovulation, was 50.0% in the polycystic ovary syndrome group and 60.0% in the non-polycystic ovary syndrome group, with no significant difference between the two groups.
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We investigated the ovulation-inducing effects of Unkei-to, a Japanese herbal medicine, in relation to the production of sex steroid hormones (17beta-estradiol and progesterone), cytokine-induced neutrophil chemoattractant (CINC/gro), interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) in the rat ovarian cell culture. Unkei-to at a concentration of 100 microg/mL significantly stimulated the secretions of 17beta-estradiol and progesterone (P < 0.01) in cultured whole ovarian dispersates. Unkei-to also enhanced the secretion of CINC/gro in a dose-dependent manner, and the secretions of CINC/gro increased significantly at concentrations of 10 and 100 microg/mL (P < 0.01). These stimulatory effects of Unkei-to on steroidgenesis and CINC/gro production are very similar to those of another Japanese herbal medicine, Toki-Shakuyaku-san. In addition, Unkei-to significantly (P < 0.01) enhanced the secretions of both IL-1beta and TNF-alpha, which are known to stimulate the secretion of CINC/gro in the ovulatory process, at concentrations of 10 and 100 microg/mL. The stimulatory effect of Unkei-to at a concentration of 100 microg/mL on IL-1beta/was significantly (P < 0.01) lower than that of Toki-Shakuyaku-san, while the stimulatory effects of these two herbal medicines at a concentration of 100 microg/mL on TNF-alpha were similar. These results show that Unkei-to can stimulate ovarian steroidgenesis and the ovulatory process by inducing the secretion of CINC/gro with IL-1beta and TNF-alpha in vitro. Unkei-to has stimulatory effects on both steroidgenesis and the ovulatory process in the ovary as well as a stimulatory effect on the hypothalamus-pituitary axis, and it may be useful for treating patients with ovulatory disorders.
Action of Unkei-to on cultured rat pituitary cells
  • Y Taketani
  • K Kugu
  • N Hayashi
  • M Mizuno
Taketani, Y., K. Kugu, N. Hayashi and M. Mizuno. Action of Unkei-to on cultured rat pituitary cells.
Recent Advances in the Pharmacology of Kampo (Japanese Herbal) Medicine
  • Y Taketani