Kou Sakuma

Changes in serum tumor necrosis factor (TNF-alpha) with kami-shoyo-san administration in depressed climacteric patients

An herbal medicine (kampo) is widely used to prevent or treat climacteric symptoms. In order to investigate the potential involvement of tumor necrosis factor (TNF)-alpha in susceptibility to mood disorder in climacteric women and to clarify the relationship between immune function and the efficacy of herbal medicine, we compared serum TNF-alpha levels in two treated groups, with and without concurrent use of herbal medicine. This study included 113 consecutive depressed menopausal patients who visited the gynecological and psychosomatic medicine outpatient clinic of the Osaka Medical College Hospital in Japan. Fifty-eight patients were administered kami-shoyo-san according to the definition of above sho. In contrast, 55 patients who were different in sho of kami-shoyo-san were administered antidepressants. Hamilton Rating Scale for depression (HAM-D) scores were determined at baseline and 12 weeks after starting treatment (endpoint). TNF-alpha concentrations were analyzed before and after 12 weeks of treatment. Kami-shoyo-san significantly increased plasma concentrations of TNF-alpha after 12 weeks of treatment, to 17.22 +/- 6.13 pg/ml from a baseline level of 14.16 +/- 6.27 pg/ml (p = 0.048). The percent change in plasma concentration of TNF-alpha differed significantly between the kami-shoyo-san therapy group and the antidepressant therapy group at 4 weeks (12.0 +/- 7.8% and -1.22 +/- 0.25%, respectively, p < 0.01), 8 weeks (19.7 +/- 3.4% and -2.45 +/- 0.86%, respectively, p < 0.01), and 12 weeks (21.3 +/- 5.4% and -6.81 +/- 2.2%, respectively, p < 0.001). We found in this study that kami-shoyo-san, an herbal medicine, increased plasma TNF-alpha levels in depressed menopausal patients. Cytokines may play various roles in mood and emotional status via the central nervous system and may be regulated by herbal medicines, although the interactions are very complex.

Comparing the Effects of Estrogen and an Herbal Medicine on Peripheral Blood Flow in Post-menopausal Women with Hot Flashes: Hormone Replacement Therapy and Gui-Zhi-Fu-Ling-Wan, a Kampo Medicine

We investigated the association between blood flow in the extremities and hot flashes, and compared change in blood flow following hormone replacement therapy (HRT) and Gui-zhi-fu-ling-wan (Keishi-bukuryo-gan), a herbal therapy in post-menopausal women with hot flashes. Three hundred and fifty-two post-menopausal women aged 46-58 years (mean: 53.4 +/- 3.6 years) with climacteric complaints participated in the study. One hundred and thirty-one patients with hot flashes were treated with HRT (64 cases) or herbal therapy (67 cases). Blood flow was measured with laser doppler fluxmetry under the jaw, in the middle finger and in the third toe. Post-menopausal women with hot flashes (129 cases) showed significantly higher blood flow under the jaw (13.6 +/- 4.13) than women without hot flashes (166 cases) (5.48 +/- 0.84) (p < 0.0001). Blood flow at this site decreased significantly with either therapy (p < 0.0001). On the other hand, the administration of Gui-zhi-fu-lingwan significantly increased (p = 0.002) the blood flow in the lower extremities, whereas HRT decreased the blood flow. Thus, we have demonstrated that Gui-zhi-fu-ling-wan did not affect the activity of vasodilator neuropeptides on sensory neurons of systemic peripheral vessels uniformly. Therefore, Gui-zhi-fu-ling-wan, rather than HRT, is suggested as an appropriate therapy for treatment of hot flashes in the face and upper body with concomitant coldness in the lower body, which is one of the symptoms of menopause.

Chai-Hu-Gui-Zhi-Gan-Jiang-Tang Regulates Plasma Interleukin-6 and Soluble Interleukin-6 Receptor Concentrations and Improves Depressed Mood in Climacteric Women with Insomnia

This study was performed to compare the effects of Chai-hu-gui-zhi-gan-jiang-tang (Saiko-keishi-kankyo-to), an herbal medicine, in improving depressed mood and on plasma interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) concentrations with those of anti-depressants in peri- and post-menopausal women. Ninety patients complaining of menopausal symptoms including insomnia who were diagnosed with mood disorder based on DSM-IV were recruited and separated into two groups (Chai-hu-gui-zhi-gan-jiang-tang group was selected on the basis of SHO for 42 cases, while anti-depressants were used for 48 cases), and plasma IL-6 and sIL-6R concentrations were determined before and after three months of the treatment. There were no significant differences in the decrease in both climacteric and Hamilton depression score after treatment between the two groups. Plasma IL-6 and sIL-6R concentrations were significantly lower in the Chai-hu-gui-zhi-gan-jiang-tang group (-34.8 +/- 15.5% and -22.4 +/- 14.6%, respectively) than in the anti-depressant group (7.5 +/- 4.8% and 2.4 +/- 3.8%, respectively) after 3 months of treatment. Correlations between rate of decrease in climacteric score and plasma IL-6 (R = 0.498, P = 0.0056) and sIL-6R (R = 0.512, P = 0.0045) concentrations were observed. Chai-hu-gui-zhi-gan-jiang-tang reduced plasma IL-6 and sIL-6R concentrations in relation to improvement of depressed mood during treatment. The findings of this study suggest that Chai-hu-gui-zhi-gan-jiang-tang has the potential to decrease morbidity by alleviation of stress reactions in peri- and post-menopausal women.

The HDL2/HDL3 ratio in menopause

The influence of the menopause on the HDL2/HDL3 ratio was assessed in association with hypertriglyceridemia.

Clinical Efficacy of Macrophage-Activating Chinese Mixed Herbs (MACH) in Improvement of Embryo Qualities in Women with Long-Term Infertility of Unknown Etiology

Despite the recent technological advances in in vitro fertilization and embryo transfer (IVF-ET), a significant proportion of women still do not become pregnant after long-term infertility, whether it is originally due to older age or other undetermined factors. In the present study, macrophage activating Chinese herbs (MACH) were evaluated for their effects on embryo qualities in women who were undergoing repeated IVF-ET because of long-term infertility. Thirty women, who had significantly low rates of developing good quality cleaved embryos and did not become pregnant after three or more cycles of Assisted Reproductive Technology (ART) procedure, were included in the study. Oral administration of MACH significantly increased the percentage of good quality early stage blastocysts (the number of grade 1 or grade 2 cleaved embryos/the number of retrieved oocytes) from 18.7 ± 16.2% to 36.1 ± 27.1% (1.9-fold increase, p < 0.01). The rate of good quality early stage blastocysts increased in all patients. In 19 patients who desired embryo transfer using late stage blastocysts, MACH significantly increased the percentage of late stage blastocysts from the initial value of 14.8 ± 11.2% to 21.1 ± 23.1% (1.4-fold increase, p < 0.05). The rate of embryonic progress into late stage blastocyst increased in 52.6% (10/19) of the patients. Furthermore, treatment with MACH significantly decreased the plasma follicle stimulating hormone (FSH) concentration on the day of oocyte retrieval from 14.4 ± 3.2 to 10.5 ± 2.4 mIU/ml (p < 0.05). No adverse events were observed with MACH supplementation, and there was no patient dropout. Administration of MACH resulted in improved embryo quality in the difficult cases. The present study demonstrates a new benefit of this herbal blend in women with refractory infertility of unknown etiology.

Efficacy of the Kampo Medicine Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a Traditional Herbal Medicine, in the Treatment of Maternity Blues Syndrome in the Postpartum Period

This study was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a Japanese traditional herbal medicine, in stabilizing postpartum psychological state. We enrolled 268 women who had a normal delivery in Osaka Medical College Hospital or its affiliated clinics and randomly assigned them to the following two groups: a group of 134 women who received Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) at a dose of 6.0 g/day and another group of 134 women without Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) (control group). We observed 2.06-fold and 1.67-fold higher incidences of depressive mood and nervousness, respectively, after delivery in the control group than in the Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) group. Within 3 weeks of postpartum, there was a significant difference in the incidences of maternity blues between the Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) group (15.7%; 21/134) and the control group (32.1%; 43/134) (p = 0.0195). No adverse effects were observed in this study. The results of this study demonstrate the beneficial clinical effects of Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) in stabilizing psychological state in the postpartum period. Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) can be expected to improve the mental health of women in the postpartum period and prevent maternity blues.

Comparison of effects of vitamin E and wen-jing-tang (unkei-to), an herbal medicine, on peripheral blood flow in post-menopausal women with chilly sensation in the lower extremities: a randomized prospective study.

We examined the association between blood flow and chilly sensation in the lower extremities, comparing the changes in blood flow induced by the vitamin E and herbal therapy (Wen-jing-tang) in perimenopausal women with chilly sensation. One hundred sixty-one perimenopausal women aged 42-61 years (mean: 50.4 +/- 3.8 years) with chilly sensation in the lower extremities participated in the study. The participants were randomized for treatment with Wen-jing-tang or a vitamin E preparation containing 600 mg tocopherol nictinate per day for 8 weeks. Blood flow measurement was performed by laser Doppler fluxmetry to determine tissue under the jaw, in the middle finger, and in the third toe. Wen-jing-tang significantly increased the peripheral blood flow in the skin surface in the tiptoe (12.8 +/- 8.8, p = 0.0068) from basal levels (6.0 +/- 5.1), although no significant change was observed in the blood flow in fingertip or under the jaw during treatment. The rate of increase of blood flow in the skin surface of in the lower extremities was significantly higher in the Wen-jing-tang treating group (116.4 +/- 46.5%) than in the vitamin E group (39.8 +/- 21.3%) (p < 0.0001). When the effects of herbal treatment and vitamin E treatment were compared in the subjects with baseline upper extremity blood flow above the mean + 1.5 SD, mean blood flow through the upper extremities was found to have been significantly decreased after Wen-jing-tang treatment (from 57.7 +/- 4.8 to 43.1 +/- 4.2, p = 0.0277), whereas it remained unchanged after treatment with vitamin E. Classical monographs described Wen-jing-tang as being particularly useful in curing chilly sensation in lower extremities. The present study using a laser Doppler fluxmeter demonstrated that treatment with this herbal medicine significantly increased blood flow through the periphery of lower extremities in patients with chilly sensation. It also showed that this herbal medicine suppresses excessive blood flow through the upper half of the body and thus stimulates restoration of physiological distribution of blood flow throughout the entire body.

Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a Traditional Herbal Medicine, Stimulates Lactation with Increase in Secretion of Prolactin but not Oxytocin in the Postpartum Period

The aim of the present investigation was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin, a traditional Japanese herbal medicine, in stimulating lactation in the postpartum period. We enrolled 82 women who had a normal delivery in Osaka Medical College Hospital, and randomly assigned them to the following two groups: a group of 41 women who received Xiong-gui-tiao-xue-yin at a dose of 6.0 g/day (Group X), and a group of 41 women who received ergometrine (methylergometrine maleate) at a dose of 0.375 mg/day (Group E). Volume of lactation was determined daily until Day 6 postpartum. Plasma prolactin and oxytocin concentration were measured at Days 1 and 6 postpartum. The results showed that volume of lactation was significantly higher in Group X than in Group E at Days 4 (p = 0.042), 5 (p = 0.038), and 6 (p = 0.046). Significant differences between Groups X and E were noted in plasma prolactin concentration at Days 1 (157.9 +/- 78.2 ng/ml and 129.1 +/- 64.8 ng/ml; p = 0.037) and 6 (167.5 +/- 95.4 ng/ml and 117.1 +/- 53.6 ng/ml; p = 0.0042) postpartum. On the other hand, at Day 1, oxytocin concentration was significantly higher in Group E than in Group X (p = 0.0024). No adverse effects were observed in this study. The results of our study demonstrate the beneficial effects of Xiong-gui-tiao-xue-yin on lactation, with increase in prolactin level without increase in oxytocin level in the postpartum period. Therefore, Xiong-gui-tiao-xue-yin can be expected to improve lactation in women in the postpartum period. Further detailed bio-pharmacological studies and clinical trials to investigate the properties of this drug are warranted.

Therapeutic Effects of Kyuki-chouketsu-in in Restoring Postpartum Physical Condition

The aim of the present investigation was to evaluate the clinical efficacy of Kyuki-chouketsu-in, a Japanese traditional herbal medicine, in restoring postpartum physical condition. We enrolled 171 women who had a normal delivery in Osaka Medical College Hospital or its affiliated clinics, and randomly assigned them to the following two groups: a group of 85 women who received Kyuki-chouketsu-in at a dose of 6.0 g/day (Group K), and a group of 86 women who received ergometrine (methylergometrine maleate) at a dose of 0.375 mg/day (Group E). The height of the uterine fundus, blood hemoglobin concentration and biochemical blood values were determined until day 6 postpartum. The height of the uterine fundus was significantly lower in women of Group K (8.9 +/- 2.4 cm) than in those of Group E (10.5 +/- 2.7 cm) on day 5 postpartum (p = 0.071). A significant difference between Groups K and E was noted in change in blood hemoglobin concentration between days 1 and 6 postpartum (4.6 +/- 7.2% in Group K; -1.57 +/- 7.3% in Group E). Significant differences between Groups K and E were noted in decrease in serum C-reactive protein (CRP) concentration and increases in serum total protein (TP) and albumin concentrations between days 1 and 6 postpartum. No adverse effects were observed in this study. The results of our study demonstrate the beneficial effects of Kyuki-chouketsu-in on physical recovery in the postpartum period. Kyuki-chouketsu-in can be expected to improve the health of women in the postpartum period. Biopharmacological research and clinical trials to investigate the properties of this drug in detail are warranted.

Efficacy of the Kampo medicine Xiong-gui-jiao-ai-tang, a traditional herbal medicine, in the treatment of threatened abortion in early pregnancy.

This study was carried out to evaluate the clinical efficacy of Xiong-gui-jiao-ai-tang (Kyuki-kyogai-to), a traditional Chinese herbal medicine, in the treatment of threatened abortion in early pregnancy. We enrolled 72 women diagnosed with threatened abortion at Osaka Medical College Hospital and assigned them at random to the following two groups: a group of 36 women who received Xiong-gui-jiao-ai-tang at a dose of 7.5 g/day and another group of 36 women who received human chorionic gonadotropin (hCG)(control group). We found that in the Xiong-gui-jiao-ai-tang group (2.9 + or - 3.5 days), the number of days required before hemostasis was reached in the uterus was significantly shorter than in the control group (10.8 + or - 8.2 days, p < 0.0001). Furthermore, the number of days required for retroplacental hematoma in the vicinity of the gestational sac to disappear was significantly shorter in the Xiong-gui-jiao-ai-tang group (9.9 + or - 7.1 days) than in the control group (23.2 + or - 12.8 days) (p < 0.0001). In retroplacental hematoma size, significant rates of reduction were obtained in both major and minor axis measurements at the 7th day of treatment for the Xiong-gui-jiao-ai-tang group compared to the control group (control vs Xiong-gui-jiao-ai-tang: major axis: 7.5 + or - 3.8% vs 42.3 + or - 10.5%; minor axis: 15.3 + or - 16.8% vs 71.5 + or - 48.2%)(p < 0.0001, each case). The results of this study demonstrated the beneficial effects of Xiong-gui-jiao-ai-tang in stabilizing early pregnancy. Xiong-gui-jiao-ai-tang can be expected to improve unstable early pregnancy with uterine bleeding and to prevent abortion.