PubMed Health⌕ Search

Biomedical subjects

K Toriizuka

Publications and source records attributed to K Toriizuka.

At least 19 recordsLinked to original sources

Anxiolytic effect of Kami-Shoyo-San (TJ-24) in mice: possible mediation of neurosteroid synthesis.

We assessed the anxiolytic effect of Kami-Shoyo-San (Jia-wei-xiao-yao-san; TJ-24), one of a traditional Chinese herbal medicine used for the treatment of menopausal anxiety, by the social interaction (SI) test in male mice. Acute administration of TJ-24 (25-100 mg/kg, p.o.), as well as the gamma-amino-butyric acidA/benzodiazepine (GABA(A)/BZP) receptor agonist diazepam (1-3 mg/kg, i.p.), dose dependently increased the SI time, respectively. The GABA(A) receptor antagonist picrotoxin blocked the effects of TJ-24 and diazepam. TJ-24-induced SI behavior was significantly blocked by the GABA(A)/BZP receptor inverse agonist Ro 15-4513 and the GABA(A)/BZP receptor antagonist flumazenil. In addition, 5alpha-reductase inhibitor finasteride potently blocked the effect of TJ-24 without attenuating the basal level by itself. These findings suggest that TJ-24 shows the anxiolytic effect through the neurosteroid synthesis followed by GABA(A)/BDZ receptor stimulations.

Animals↗

Effects of hokoei-to (pugongying-tang), a Kampo formula, on monoamine content in brain regions and mitogenic activity of splenic lymphocytes in ovariectomized mice.

Hokoei-to (pugongying-tang) is one of the Kampo formulae clinically used for gynecological disturbances such as lack of lactation and mammary swelling. We investigated the effect of hokoei-to on the nervous and immune systems in ovariectomized mice as a climacteric disorder model. Hokoei-to suppressed the decrease of monoamines in the ventral hippocampus and dorsal hippocampus of ovariectomized mice. It was shown that the hokoei-to could improve the metabolic turnover of dopamine. The mitogenic activity of lymphocytes in the spleen was reduced after ovariectomy; a suppression of this reduced activity was observed in the group given hokoei-to.

3,4-Dihydroxyphenylacetic Acid↗

Long term effects of Toki-shakuyaku-san on brain dopamine and nerve growth factor in olfactory-bulb-lesioned mice.

We used olfactory-bulb-lesioned mice induced by intranasal irrigation with zinc sulfate as a model of dementia, to investigate the effects of Toki-shakuyaku-san (TSS) on monoamines and nerve growth factor (NGF) in brain regions. TSS was given daily through the drinking water for either 1, 2, 3, 4 or 8 weeks from the day after olfactory lesion. The administration of TSS significantly suppressed the decrease of 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in olfactory bulb of olfactory-lesioned mice at 1 week, and tended to suppress the decrease of DOPAC and HVA during the experimental session. However, the administration of TSS had no influence on dopamine contents. NGF contents in the olfactory bulb were increased after the irrigation, and the value returned to the same level as the control at 8 weeks after. Although the NGF contents in the olfactory bulb of TSS-treated mice were immediately increased at 1 and 2 weeks, the value returned to normal level within 3 weeks. These findings indicate that oral administration of TSS prevents the reduction of dopamine metabolites, DOPAC and HVA, and immediately increased NGF contents in the olfactory bulb. This suggested that TSS treatment promotes the NGF contents in olfactory nerves and rescue the neurons from damage.

3,4-Dihydroxyphenylacetic Acid↗

Effect of gravity change on the production of thrombopoietic growth factors.

It is reported that the stay in the space develops anemia, thrombocytopenia, and altered function and structure of red blood cell. The mechanism of these abnormalities was not clarified yet. The cloning of the thrombopoietin (TPO), followed by the analysis of TPO and c-mpl (its cellular receptor) knockout mice confirmed its role as the primary regulator of thrombopoiesis. TPO has been shown to stimulate both megakaryocyte colony growth from marrow progenitor cells and the maturation of immature megakaryocyte to form functional platelet. This process includes the massive cytoskeletal rearrangement, such as proplatelet formation and fragmentation of proplatelet. In this study we have focused on the production of thrombopoietic growth factors in mice those were exposed to gravity change by parabolic flight (PF).

Animals↗

Effects of Kampo medicine, Toki-shakuyaku-san (Tang-Kuei-Shao-Yao-San), on choline acetyltransferase activity and norepinephrine contents in brain regions, and mitogenic activity of splenic lymphocytes in ovariectomized mice.

We investigated the effects of Toki-shakuyaku-san (TSS, Tang-Kuei-Shao-Yao-San in Chinese), Japanese traditional herbal medicine, on the nervous and immune systems in ovariectomized mice as a climacteric disorder model. Female C57BL/6 mice were ovariectomized (OVX) and TSS was given daily through the drinking water for either 10 or 20 days from the day after ovariectomy. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for choline acetyltransferase (ChAT) activity and norepinephrine contents. The mitogenic activities, alkaline phosphatase activity and 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H terazolium bromide (MTT) activity, in splenic lymphocytes has also measured. Furthermore, the effects of TSS on learning and memory ability were studied by the step-through type passive avoidance test. As the results, the administration of TSS significantly suppressed the decrease of ChAT activity in the cerebral cortex (CC) and the dorsal hippocampus (DH) of ovariectomized mice at 10 days after ovariectomy, however no significant effect was observed at 20 days after ovariectomy. Norepinephrine contents in OVX group were decreased at 10 and 20 days after ovariectomy in the CC and the ventral hippocampus (VH). The administration of TSS significantly suppressed the decrease of norepinephrine contents at 20 days after ovariectomy. The mitogenic activities of lymphocyte in spleen were increased at 10 days after ovariectomy, and decreased at 20 days after ovariectomy. However, the suppression of these changes was observed in the group given TSS. The mean latent period was also shortened in the passive avoidance test in the OVX group, but TSS treated group improved mean latency. From these observations, it is inferred that administration of TSS brings on the synthesis of acetylcholine and norepinephrine in the CC and hippocampus, and may improve the memory related behavior and the abnormalities in lymphocytes in the models of the climacteric disorder.

Animals↗

Potentiation of brain acetylcholine neurons by Kami-Untan-To (KUT) in aged mice: implications for a possible antidementia drug.

The effects of a traditional Japanese herbal medicine, Kami-Untan-To (KUT), on brain choline (Ch) and Acetylcholine (ACh) levels in aged mice were examined. Further, the expression of choline acetyltransferase (ChAT) in the medial septum (MS), the vertical limbs of the diagonal band of Broca (VDB), and the nucleus basalis Meynert (NBM) was examined by immunohistochemistry. Following an oral administration of KUT to the aged mice for 3 months, ACh levels in the cortex, striatum and hippocampus were increased significantly. The density of ChAT-immunoreactive cells located in MS, VDB, and NBM in the KUT-treated group was increased significantly as compared to the non-treatment group. The survival rate of aged mice was significantly higher in the KUT-treated group as compared to that in the nontreated group. Our results suggest that KUT potentiates the brain acetylcholinergic system, and may become a possible anti-dementia drug.

Acetylcholine↗

[Menopause and anxiety: focus on steroidal hormones and GABAA receptor].

In the menopause transition, around 35% of women will seek medical help for menopausal symptoms. At the climacteric, various symptoms such as forgetfulness, anxiety, depressive neurosis, abnormal sensation, hot flush and sleeplessness are often observed due to hypofunction of the ovaries. There is some indication that women become more anxious during times of relatively low level of estrogen and progesterone such as premenstrual syndrome, premenstrual dysphoric disorder, maternity blues and menopausal state. The exact mechanism behind it is still unclear but is probably related to the decrease of ovarian hormones, which may be triggering psychiatric mood disorders. It is known that ovarian hormones act on specific areas of the brain and appear to act as anxiolytics. Certain progesterone metabolites are anesthetic and have antiepileptic and anxiolytic properties. These steroids modulate the type A gamma-aminobutyric acid (GABAA)/benzodiazepine receptor. This may help explain the increased frequency of anxiety disorders and mood disorders in the early postmenopausal period. In addition, estrogen also improves memory and performance in patients with mild Alzheimer's dementia. These effects can be related to amplifying effects of estrogen on excitatory amino acids in the brain. This is suggested that gonadal steroidal hormones seemed to be one of the essential substances for the maintenance of the limbic system and forebrain function which regulated anxiety, mood, memory and cognitive functions in menopausal women.

Anti-Anxiety Agents↗

[A new interventional strategy for Alzheimer's disease by Japanese herbal medicine].

A Japanese herbal medicine termed "Kami-Umtan-To (KUT)" was first described in Japanese literature in 1626, KUT consists of 13 different herbs, and it has been used for a long time in the treatment of a variety of neuropsychiatric problems including neurosis and insomnia. Recently, Yabe et al. have demonstrated that KUT increased both choline acetyltransferase (ChAT) and nerve growth factor at the protein and mRNA levels in cultured rat brain cells. Moreover, the same research group has reported that KUT improved mean latency on passive avoidance test in both basal for brain lesioned and aged rats. KUT significantly improved the survival rate, and increased the number of ChAT-positive neurons in aged rats. Here, we report a 12-month open clinical trial of KUT and combination of estrogen, vitamin E and NSAID to aim at slowing down the progression of Alzheimer's disease (AD). Twenty AD patients (MMSE score: 18.6 +/- 5.8) received extracts from original KUT herbs, and 7AD patients (MMSE score: 21.3 +/- 2.8) were placed on the combination therapy. Rate of cognitive decline as measured by change in MMSE score per year was significantly slower (p = 0.04, ANOVA) in the KUT group (1.4 points) and the combination group (0.4 points) as compared to 4.1 points in 32 control AD patients (MMSE score: 20.8 +/- 5.6) who received no medicines for AD. Any of CSF measures including tau. and A beta 1-42 did not differ significantly after KUT therapy. The efficacy of the KUT therapy was most obvious at 3 months. Our results suggest that traditional Japanese herbal medicine(s) may serve a new interventional strategy for AD.

Aged↗

Effect of Shimotsu-to (a Kampo medicine, Si-Wu-Tang) and its constituents on triphasic skin reaction in passively sensitized mice.

Previous studies have reported that mice passively sensitized with anti-DNP (dinitrophenol) IgE antibody exhibited IgE-mediated skin reaction with an immediate phase response (IPR) at 1 h and a late phase response (LPR) at 24 h after the challenge of DNFB (dinitrofluorobenzene). We recently found that a third phase inflammatory reaction with intense and persisting infiltration of eosinophils, named very late phase response (vLPR), was induced by DNFB challenge peaking at 8 days. In this study, we examined the effects of a Kampo medicine, Shimotsu-to (Si-Wu-Tang), and its constituent crude drugs on triphasic skin reaction in passively sensitized mice. Shimotsu-to inhibited ear swelling in LPR and vLPR after DNFB challenge in a dose-dependent manner, and slightly diminished the scratching behavior considered to be associated with pruritus in IPR. The inhibitory effect on LPR and vLPR was partly due to Cnidii Rhizoma (Senkyu) in Shimotsu-to formulation, especially its fraction 5 containing cnidilide. On the other hand, Angelicae Radix (Toki) rather than Cnidii Rhizoma (Senkyu) in Shimotsu-to, inhibited the scratching behavior, although it did not inhibit the ear swelling in IPR. These findings indicate that the Shimotsu-to formulation is useful for the inhibition of cutaneous inflammatory diseases.

Animals↗

Effects of acupuncture on peripheral T lymphocyte subpopulation and amounts of cerebral catecholamines in mice.

The aim of this study was to investigate the effects of acupuncture on peripheral lymphocyte subpopulations and cerebral catecholamines. In order to examine the effects of acupuncture, two experiments were performed. Experiment 1: Eighteen female mice (strain; C57BL/6) at the age of 7 weeks were divided three groups, (a) sham operated (control; n=6), (b) ovariectomized (OVX; n=6), and (c) ovariectomized and stimulated by subcutaneous needles on acupuncture point, Shenshu (BL23) at the both sides of the back for 20 days (OVX+Acu; n=6). These animals were sacrificed at 20 days after needle insertion, and the splenic lymphoid cells were examined by two-color flow cytometry, using monoclonal antibodies (mAb) to the cell surface antigens, CD3, CD4, CD8a and NK1.1 (CD56). In the ovariectomized (OVX) group, the peripheral CD4/CD8 ratio was significantly increased and the ratio of natural killer (NK) cells (CD3-NK1.1+; CD3 negative, NK1.1 positive) to T lymphocytes was decreased compared to the sham control group. In the ovariectomized with needle insertion (OVX+Acu) group, the CD4/CD8 ratio was reduced, but the NK cells ratio was not changed compared to the OVX group. Experiment 2: To investigate the acute effects of subcutaneous needle insertion, male C57BL/6 mice (7 weeks old) were used (n=6, each group). The acupuncture points Shen-shu (BL23) on the backs of the male mice were also stimulated by subcutaneous needles for 3 and 7 days. As a result, the CD4/CD8 ratio was significantly decreased at day 3 and day 7, compared to the control group. On the other hand the NK cells ratio and activated T-cells were increased at day 7. The mitogenic activities in the splenic lymphocytes were also increased by acupuncture stimulation at day 3. Catecholamine contents in the hippocampus were measured by high performance liquid chromatography with the electro-chemical detector (ECD-HPLC) method. No significant change was observed in either dopamine contents or norepinephrine; however, dopamine metabolite, homovanillic acid (HVA) and DOPAC (3,4-dihydroxyphenylacetic acid) were increased at day 3. The study suggests that acupuncture has effects on peripheral lymphocyte subpopulations and may modulate mitogenic activity. In addition, acupuncture may stimulate dopamine turnover.

Acupuncture Therapy↗

Acupuncture inhibits the decrease in brain catecholamine contents and the impairment of passive avoidance task in ovariectomized mice.

The effects of acupuncture on the disorders elicited by abnormalities of endocrine system were investigated in ovariectomized mice. Female mice (strain; C57BL/6) were ovariectomized (OVX) and acupuncture points, Shenshu ([Japanese pictograph see text] : BL23) on both side of the back were continuously stimulated by subcutaneous needles for 20 days. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for catecholamine contents by high performance liquid chromatography with electro chemical detector (ECD-HPLC). The mitogenic activities of splenic lymphocytes were measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTS) assay and alkaline phosphatase (ALP) assay. Furthermore, the effects of needle stimulation on learning and memory ability were studied by the step-through type passive avoidance test. Norepinephrine and dopamine contents in the frontoparietal cerebral cortex, ventral hippocampus and olfactory bulb were decreased in the OVX group, and both MTS activity and ALP activity were decreased 20 days after ovariectomy. The mean latent period was also shortened in the passive avoidance test in the OVX group. However, applying needle stimulation increased norepinephrine and dopamine contents in the brain regions, and enhanced mitogenic activities of splenic lymphocytes. The stimulation also improved memory-related behavior. It was concluded from this study that after mice were stimulated by subcutaneous needle insertion, overall changes were observed in central nervous system (including retention of memory) and immune functions. The study suggests that acupuncture improves the memory loss and decrease of immune responses accompanying aging and/or menopause, and the that it may have an important role in medical care for the elderly.

Acupuncture Therapy↗

Effects of lycopene, a carotenoid, on intrathymic T cell differentiation and peripheral CD4/CD8 ratio in a high mammary tumor strain of SHN retired mice.

We previously reported that lycopene, one of the carotenoids, significantly suppressed the development of spontaneous mammary tumors of mice and the contribution of lycopene to the maintenance of physical homeostasis was suggested. In this study, we investigated the effects of lycopene on the intrathymic and peripheral T cell subpopulation as immunoregulatory parameters. In tumorous control mice, inactivation of intrathymic T cell differentiation, an increase of the percentage of CD4+ CD8+ cells and a decrease of CD4+CD8+ cells were observed. On the other hand, in the lycopene-treated mice, the abnormal intrathymic T cell differentiation was recovered and brought to non-tumorous levels. The peripheral CD4/CD8 ratio was partially augmented by lycopene treatment which resulted from an increased CD4+ subpopulation. These observations suggest that one of the immunomodulating roles of lycopene is to normalize the change of intrathymic T cell differentiation caused by tumorigenesis.

Animals↗

Effects of Kampo medicines on the clearance of circulating immune complexes in mice.

Toki-Shakuyaku-san (TSS), a Japanese (Kampo) formulation which consists of six herbs, was administered orally to MRL Mp-lpr/lpr mice for 6 weeks. Clearance was measured by in vivo enzymatic immune complex clearance (EIC) assay. Glucose oxidase-anti-glucose-oxidase complexes (GAG), as a model of immune complexes (ICs), was injected into mouse tail veins and at intervals thereafter the enzyme activity of the GAG remaining in the circulation were estimated. The half life (T1/2) of GAG from the circulation was significantly shortened in the TSS-treated group. Furthermore, the amount of circulating immune complexes, measured by anti-mouse C3 ELISA, tended to decrease in the TSS-treated group. We also evaluated three other Kampo formulas, but no significant effect was observed for these formulations. We then examined the activity of the individual herbs in TSS and in formulations excluding one component herb. No significant changes were observed with individual herbs. On the other hand, the activity observed in the TSS-treated group disappeared in the TSS minus Angelicae Radix formulation and the TSS minus Atractylodis Lanceae Rhizoma formulation. These observations indicate that TSS is a potent formula and its enhancing activity on ICs clearance is strengthened by both Angelicae Radix and Atractylodis Lanceae Rhizoma.

Administration, Oral↗

Erythrocyte antioxidant enzymes are reduced in patients with rheumatoid arthritis.

Superoxide dismutase, catalase, and glutathione peroxidase activities were determined in erythrocytes isolated from 17 patients with rheumatoid arthritis (RA) and from 19 with osteoarthritis of the knee joints as controls. In a comparison of the 2 groups, it was found that the activities of these 3 antioxidant enzymes were significantly decreased in patients with RA. This indicates that erythrocytes in patients with RA might be injured more easily by oxy radicals which are endogenously generated in red blood cells.

Aged↗