Tetsuro Oikawa

I.c.v. administration of orexin-A induces an antidepressive-like effect through hippocampal cell proliferation.

A decrease in orexin-A (OX-A) levels has been reported to be associated with depression. It is also well known that stress and depression can disrupt neurogenesis in the dentate gyrus of the hippocampus; however, it is unclear how OX-A is involved in depression and/or neurogenesis. In the present study, we investigated the effect of i.c.v. administration of OX-A on the forced swimming test (FST), an accepted behavioral screen of antidepressant-like activity, and on the cell proliferation with bromodeoxyuridine (BrdU) in the dentate gyrus at 4 days after i.c.v. administration of OX-A. OX-A administration (140 pmol/mouse) led to a significant reduction in animal immobility in the FST, without affecting spontaneous locomotor activities or serum corticosterone levels. In addition, the number of BrdU-positive cells in the dentate gyrus was significantly increased in OX-A-treated mice in vivo; however, OX-A did not affect the percentage of doublecortin-positive cells in the dentate gyrus. The proliferation of neural progenitor cells derived from rat fetal brain was not affected by OX-A treatment in vitro, and the orexin receptor 1 (OXR1) protein was not expressed in these cells. Treatment with the OXR1 antagonist SB-334867 (30 mg/kg, i.p.) blocked both the OX-A-induced decrease in the immobility of FST and increase in BrdU-positive. Moreover, the OX-A-induced increase in neuropeptide Y (NPY)-positive cells in the hilus of the dentate gyrus was blocked by SB-334867. These results suggest that OX-A induces an antidepressive-like effect, at least in part, via the enhancement of cell proliferation in the dentate gyrus. These effects of OX-A also may be partly relevant to the regulation of the NPY system in the hilus of the dentate gyrus.

Antidepressant-like Effect of l-perillaldehyde in Stress-induced Depression-like Model Mice through Regulation of the Olfactory Nervous System

Perillae Herba (a leaf of Perilla frutescens) has been prescribed as one of the component herbs in certain Kampo (Japanese herbal) medicines that are used clinically for the improvement of depressive mood. l-Perillaldehyde (PAH) is a major component in the essential oil containing in Perillae Herba, but its antidepressant-like effect has not been reported. To clarify the antidepressant-like effect of PAH, the inhaled effect of PAH on stress-induced depression-like model mice prepared by subjection to a combination of forced swimming and chronic mild stresses was investigated. The degree of the depression-like state was measured by the animals duration of immobility using a forced swimming test. Inhalation of PAH (0.0965 and 0.965 mg/mouse/day, 9 days) significantly shortened the duration of immobility of the depression-like model mice and did not affect locomotor activity. However, another odor substance, cinnamaldehyde containing in Cinnamomi Cortex, exhibited no reduction in the immobility. The reduction in the immobility induced by the inhalation of PAH was prevented on anosmia-induced mice prepared by intranasal irrigation with zinc sulfate. These results suggest that the inhalation of PAH shows antidepressant-like activity through the olfactory nervous function.

Daikenchuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus by anti-inflammatory action through nicotinic acetylcholine receptors

BackgroundDaikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal medicine, is prescribed for patients with postoperative ileus (POI) and adhesive bowel obstruction following abdominal surgery. Several mechanisms for the amelioration of POI by DKT have been suggested; however, it has remained unclear whether DKT shows anti-inflammatory effects in POI. In the present study, we investigated the effects of DKT in a mouse POI model and attempted to clarify the detailed mechanisms of action.MethodIntestinal manipulation (IM) was applied to the distal ileum of mice. DKT was administered orally to the animals 4 times before and after IM. Gastrointestinal transit in vivo, leukocyte infiltration, cytokine mRNA expression and gastrointestinal motility were analyzed. We also investigated the effects of the α7nAChR antagonist methyllycaconitine citrate (MLA) on the DKT-mediated ameliorative action against POI, and we studied the effects of DKT on inflammatory activity in α7nAChR knockout mice.ResultsDKT treatment led to recovery of the delayed intestinal transit induced by IM. DKT significantly inhibited the infiltration of neutrophils and CD68-positive macrophages, and inhibited mRNA expressions of TNF-α and MCP-1. MLA significantly reduced the anti-inflammatory action of DKT, and the amelioration of macrophage infiltration by DKT was partially suppressed in α7nAChR knockout mice.ConclusionsIn conclusion, in addition to the gastrointestinal prokinetic action, DKT serves as a novel therapeutic agent for POI characterized by its anti-inflammatory potency. The DKT-induced anti-inflammatory activity may be partly mediated by activation of α7nAChR.

Clinical efficacy of Kampo medicine (Japanese traditional herbal medicine) in the treatment of primary dysmenorrhea

Objective:  We intended to evaluate the clinical efficacy of Kampo medicine, a Japanese traditional herbal medicine, for primary dysmenorrhea which was prescribed according to the Kampo diagnosis, with classification of its severity.

Hangekobokuto (Banxia-houpo-tang), a Kampo Medicine that Treats Functional Dyspepsia

Although abdominal bloating is one of the most bothersome symptoms experienced by patients with functional dyspepsia (FD), therapeutic drugs to relieve abdominal bloating have not been established. We investigated the Kampo (Chinese herbal) medicine, Hangekobokuto (Banxia-houpo-tang, HKT) for patients with FD from the standpoint of bowel gas retention. The bowel gas volume calculated from a plain abdominal radiogram (gas volume score, GVS) in FD patients was significantly higher than that in healthy subjects. Two week administration of HKT in the FD patients showed a significant decrease of GVS. Furthermore, gastrointestinal symptoms, especially symptoms of abdominal pain, indigestion and constipation, all of which are closely related to abdominal bloating, improved significantly in FD patients after the administration of HKT. These results suggest that HKT improves abdominal bloating accompanied by the reduction of bowel gas in FD patients.

Discrepancy Between Clinical Course and Drug-Induced Lymphocyte Stimulation Tests in a Case of Saireito-Induced Liver Injury Accompanied by Sjögren Syndrome

BACKGROUND Saireito consists of components of shosaikoto and goreisan. There are several reports of liver injury caused by shosaikoto and saireito, whereas cases caused by goreisan are rarely seen. PATIENT A 70-year-old woman suffered from sicca of the eyes and oral cavity that arose in 2003. In June 2004, we diagnosed her as having Sjögren syndrome on the basis of Schirmers test, salivary scintigraphy, presence of anti-SS-A/Ro antibody, and subjective symptoms. Although a muscarinic agonist was commenced, her sicca symptoms did not improve. INTERVENTIONS In February 2008, 7.5 g/day of shosaikoto extract granules (for ethical use, Tsumura & Co., Tokyo, Japan) was introduced. Her symptoms and laboratory data did not change. The next month, the treatment was replaced by 9.0 g/day of saireito extract granules (for ethical use, Tsumura & Co., Tokyo, Japan). RESULTS After 10 weeks, elevation of liver enzymes was observed. On suspicion of drug-induced liver injury (DILI), saireito was withdrawn, and the patients liver enzymes returned to normal the next month. Drug-induced lymphocyte stimulation tests (DLSTs) for saireito, shosaikoto, and goreisan were all positive. CONCLUSIONS The clinical course suggested allergy to the goreisan component of saireito. It is important to be aware of the limitation of DLST as a diagnostic tool for DILI, especially for herbal medicines.

Effects of goshuyuto on lateralization of pupillary dynamics in headache.

Autonomic nervous imbalance is implicated in chronic headache. We investigated the effects of goshuyuto-a representative Kampo medicine for headache-on the lateralization of the pupillary autonomic nervous system by using binocular infrared video pupillography. Patients with chronic headache were administered goshuyuto extract for 1 month (1st stage). Goshuyuto was discontinued for 1 month, following which the patients were randomly divided into 2 groups: placebo and goshuyuto. In the 2nd stage, the respective groups were administered placebo or goshuyuto for 3 months. The average laterality of the pupillary dynamics decreased significantly in the goshuyuto group. These results suggest that the reduction of the difference in pupillary autonomic balance between the left and right eyes might be one of the action mechanisms of goshuyuto to relieve chronic headache.

Kososan, but not milnacipran, elicits antidepressant‐like effects in a novel psychological stress‐induced mouse model of depression

Mild or moderate depressive symptoms are often resistant to treatment with currently available antidepressants. We constructed a novel animal model of depression induced by the exposure of mice to psychological stress and evaluated the antidepressant efficacy of kososan and milnacipran.

Zingiberis Siccatum Rhizoma, the active component of the Kampo formula Daikenchuto, induces anti-inflammatory actions through α7 nicotinic acetylcholine receptor activation

We previously reported that Daikenchuto (DKT), a gastrointestinal prokinetic Japanese herbal (Kampo) medicine used for the treatment of postoperative ileus (POI), has characteristic potent anti‐inflammatory activity. This effect may be partly mediated by the activation of α7 nicotinic acetylcholine receptor (nAChR). In this study, we identified the specific herbs in DKT that induce anti‐inflammatory action.

Antidepressive‐like effect of volatile components of kososan in a mouse model of stress‐induced depression

Kososan (Xiang‐Su‐San in Chinese), a kampo (traditional Japanese herbal) medicine, contains large amounts of unique volatile components (termed KSv). This study evaluated the antidepressive‐like effects of KSv alone or in combination with the water‐soluble extracts of kososan (termed KSw), neither of which is fully known, in a mouse model of stress‐induced depression.