Kampo medicine (Chinese herbal medicine) has been reported to be effective in the treatment of pituitary-ovarian dysfunction in young women, the treatment of infertility in women during the reproductive age and the treatment of several undefined symptoms in peri- and postmenopausal women. It has been considered that both the diagnosis and treatment of ovulatory failure in adolescent girls or young women are necessary for the sake of future fertile capacity. However, treatment for the above patients is not easy as steroid hormones and strong stimulators of ovulation should not be recommended because of the several side effects it causes. Furthermore, young women, especially teenagers, seem to be reluctant to visit gynecology clinics. Recent publications such as the Women's Health Initiative (WHI), HERS study and its follow-up HERS II study, and European clinical research group published Million Women study resulted in a major shift in the recommendation on hormone replacement therapy to alternative medicine such as herbal medicine (Kampo medicine) in the treatment of peri- and postmenopausal women with several undefined symptoms and ovariectomy by the reason of substantial risks for cardiovascular disease and breast cancer during the treatment with popular hormone replacement therapy in United States and elsewhere. In modern Western medicine, it is not rare that hormone replacement therapy is used to treat all undefined symptoms, e.g. headache, hot flushes, dizziness, and chilly sensation. Kampo medicine first determines the condition underlying a given symptom in accordance with the Kampo theory.
A number of herbal medicines have been used for many centuries in China and Japan for the treatment of menstrual disorders, infertility and undefined symptoms, e.g. hot flushes and chilly sensation. In general, the traditional Chinese herbal prescriptions are rather inexpensive and safe with little side effects, and have properties for normalizing biological balances.
Unkeito is known to stimulate the synthesis and release of gonadotropins in the rat pituitary. On the other hand, Unkeito is also known to be effective in various menstrual disorders, abnormal uterine bleeding, and infertility by the appropriate regulation (stimulation or suppression) of pituitary-ovarian endocrine axis in humans. In the treatment of several types of ovulatory failure, recent dynamic studies have revealed the mechanism by which Unkeito regulates human's endocrine axis. Furthermore, some human studies revealed the mechanism by which Unkeito improves hot flushes and chilly sensation in the extremities through the regulation of the surface blood flow.
In this paper, we critically review the clinical data available (to date) in order to assess the efficacy of Unkeito in inducing ovulation in several types of ovulatory failure and the efficacy for improving chilly sensation.

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The constituents of Bu-Shen-Jian-Gu-Tang and their inhibitory activities on osteoclast-like cell formation were investigated. Bu-Shen-Jian-Gu-Tang was fractionated by a Diaion HP-20 column with EtOH-H₂O, and the 60% and 90% EtOH-H₂O fractions showed more potent inhibitory activities on osteoclast-like cell formation and bone resorption. Chemical investigation of these two fractions resulted in the isolation of 11 compounds, for which the structures were elucidated based on spectroscopic analysis and chemical reactions. The inhibitory activities of the isolated compounds on osteoclast-like cell formation were evaluated. Among the eleven compounds, icariin (1), icarisid II (2), 2"-O-rhamnosylicariside II (3), kaempferol (8), chikusetsusaponin IVa (10) and chikusetsusaponin V (11) showed potent inhibitory activities at a concentration of 2 μM without toxic effects. The preventive effect of Bu-Shen-Jian-Gu-Tang on bone loss may be due to the inhibitory activities of these compounds.

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The traditional Chinese medicine, Tokishakuyakusan (TS; Dang-Gui-Shao-Yao-San in Chinese), is frequently applied in obstetrics and gynecology departments in Japanese hospitals. The novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) that is transiently induced by the gonadotropin surge, plays an important role in the synthesis of estradiol and progesterone in ovarian granulosa cells. Here, we investigated the effect of TS on PACAP in hypophysectomized (HPX) or ovariectomized (OVX) female rats. The weight of the hypothalamus from HPX rats administered with oral TS for one week did not appreciably change. In contrast, TS decreased the weight of the hypothalamus that was increased by ovariectomy. Moreover, TS promoted the expression of PACAP and PACAP type I receptor (PAC₁) mRNA and protein in the hypothalamus of HPX and OVX rats. However, bone metabolism that was increased by removing the pituitary or ovaries was not suppressed. These findings suggest that TS promotes the secretion of gonadotropic hormone through the expression of hypothalamic PACAP, PAC₁ mRNA and PAC₁ protein.

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The prescription Tokishakuyakusan (TS; Dang-Gui-Shao-Yao-San in Chinese) is widely used in traditional Chinese medicine. Since delay of ovarian follicle maturation and fall of bone density are known in hypophysectomized (HPX) rats, we investigated the effects of TS on ovaries in HPX rats. Although TS did not recover the ovary weight decreased by hypophysectomy, it recovered the uterine weight. Two weeks after hypophysectomy, the expression of steroidogenic acute regulatory protein (StAR) mRNA was decreased, but recovered by administration of TS. On the other hand, the expression of pituitary adenylate-cyclase activating polypeptide receptor type I (PAC₁) and progesterone receptor (PR) mRNA was increased, but reduced by administration of TS. However, the expression of estrogen receptor (ERα) mRNA did not synchronize with PAC₁ mRNA and PR mRNA expression. Moreover, TS was demonstrated to promote the follicle maturation by histrogical analysis, and to decrease significantly the urinary deoxypyridinoline (DPD) level. These findings suggest that TS promotes the maturation of follicles and suppresses the bone metabolism associated with pituitary hormones.

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Shakuyakukanzoto(SKT) consists of two kinds of crude drugs, Shakuyaku and Kanzo. SKT is used for leg cramps, stomachache, and menstrual colic pain. Clinically, different combination ratios of Shakuyaku and Kanzo exists, including the use of Kagenho (modified formulations) of an other Kampo formulation. But it remains un clear which ratio is best to apply.
We investigated the best combination ratio of Shakuyaku and Kanzo using mouse for the estimation of intestinal tract movement. SKT composed of Shakuyaku 50% and Kanzo 50% significantly decreased intestinal tract movement, comparable to atropin. These data suggest that these combination ratios of Shakuyaku and Kanzo work best for suppressing peristaltic motion.
In this study, we demonstrated that the combination ratio of Shakuyaku and Kanzo used as the formulation is reasonable from the standpoint of pharmacological background.

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