Metallothionein synthesis increased by Ninjin-yoei-to, a Kampo medicine protects neuronal death and memory loss after exposure to amyloid ß1-42.

BACKGROUND: It is possible that increased synthesis of metallothioneins (MTs), Zn2+-binding proteins is linked with the protective effect of Ninjin-yoei-to (NYT) on Zn2+ toxicity ferried by amyloid ß1-42 (Aß1-42). METHODS: Judging from the biological half-life (18-20 h) of MTs, the effective period of newly synthesized MT on capturing Zn2+ is estimated to be approximately 2 days. In the present paper, a diet containing 3% NYT was administered to mice for 2 days and then Aß1-42 was injected into the lateral ventricle of mice. RESULTS: MT level in the dentate granule cell layer was elevated 2 days after administration of NYT diet, while the administration reduced intracellular Zn2+ level increased 1 h after Aß1-42 injection, resulting in rescuing neuronal death in the dentate granule cell layer, which was observed 14 days after Aß1-42 injection. Furthermore, Pre-administration of NYT diet rescued object recognition memory loss via affected perforant pathway long-term potentiation after local injection of Aß1-42 into the dentate granule cell layer of rats. CONCLUSION: The present study indicates that pre-administration of NYT diet for 2 days increases synthesis of MTs, which reduces intracellular Zn2+ toxicity ferried by extracellular Aß1-42, resulting in protecting neuronal death in the dentate gyrus and memory loss after exposure to Aß1-42.

A case of improvement of clozapine-induced low leukocyte counts by adenine, cepharanthin and ninjin-yoei-to in a patient with treatment-resistant schizophrenia.

BACKGROUND: Although clozapine is the optimal drug for patients with treatment-resistant schizophrenia, the drug has harmful adverse effects such as leukopenia. Adenine and cepharanthine are known to be effective for radiation- or drug-induced leukopenia. Furthermore, ninjin-yoei-to, a Chinese herbal medicine, augments the production of granulocyte-macrophage colony-stimulating factor. Thus, these drugs may be useful for clozapine-induced leukopenia. CASE PRESENTATION: A 21 years-old woman with schizophrenia was hospitalized for initiation of clozapine treatment. Despite concomitant use of adenine, cepharanthine, and lithium carbonate having activities of increasing leukocytes, a decrease in leukocyte counts occurred after the initiation of clozapine. Additional administration of ninjin-yoei-to increased leukocyte counts, which prevented the development of leukopenia. CONCLUSIONS: This is the first case that concomitant use of adenine, cepharanthin, and ninjin-yoei-to exhibited the effectiveness of reversing the decrease in leukocytes caused by clozapine. Monitoring leukocyte counts and preventing leukopenia are essential for successful treatment with clozapine for refractory schizophrenia. These medicines may be a potential option for preventing clozapine-induced leukopenia.

Preventive effect of Ninjin-yoei-to, a Kampo medicine, on amyloid ß1-42-induced neurodegeneration via intracellular Zn2+ toxicity in the dentate gyrus.

Ninjin-yoei-to (NYT), a Kampo medicine, has ameliorative effects on cognitive dysfunction via enhancing cholinergic neuron activity. To explore an efficacy of NYT administration for prevention and cure of Alzheimer's disease, here we examined the effect of NYT on amyloid ß1-42 (Aß1-42)-induced neurodegeneration in the dentate gyrus. A diet containing 3% NYT was administered to mice for 2 weeks and human Aß1-42 was intracerebroventricularly injected. Neurodegeneration in the dentate granule cell layer of the hippocampus, which was determined 2 weeks after the injection, was rescued by administration of the diet for 4 weeks. Aß staining (uptake) was not modified in the dentate granule cell layer by pre-administration of the diet for 2 weeks, while Aß1-42-induced increase in intracellular Zn2+ was reduced, suggesting that pre-administration of NYT prior to Aß injection is effective for reducing Aß1-42-induced Zn2+ toxicity in the dentate gyrus. As a matter of fact, Aß1-42-induced neurodegeneration in the dentate gyrus was rescued by pre-administration of NYT. Interestingly, the level of metallothioneins, intracellular Zn2+-binding proteins, which can capture Zn2+ from Zn-Aß1-42 complexes, was elevated in the dentate granule cell layer by pre-administration of NYT. The present study suggests that pre-administration of NYT prevents Aß1-42-mediated neurodegeneration in the dentate gyurs by induced synthesis of metallothioneins, which reduces intracellular Zn2+ toxicity induced by Aß1-42.

Blood Making Effect of Ninjin-yoei-to(Ren-shen-yang-rong-tang) as Monotherapy in Obstetric and Gynecologic Patients with Anemia / 日本東洋医学雑誌

Twelve patients with iron deficiency anemia, who were unable to take iron drugs due to side effects or other reasons, were treated with oral doses of Ninjin-yoei-to (Ren-shen-yang-rong-tang), a Kampo Japanese herbal medicine, and were followed up. The onset of the blood-making effect of Ninjin-yoei-to monotherapy is slower than that of iron drug monotherapy or combination therapy with iron drugs and Ninjin-yoei-to. However, some clinical improvements in anemia were observed after continued therapy with Ninjin-yoei-to. Some patients showed normal blood counts 12 weeks after treatment with Ninjin-yoei-to. In addition, it was observed that some clinical symptoms that accompany anemia, such as dull headache and chill in the extremities, showed early improvement. Several other reports have documented similar effects with Ninjin-yoei-to. It seems that the pharmacological actions of Ninjin-yoei-to, such as increasing the absorption of nutrients required for blood-making by appetite stimulation and activation of bone marrow hematopoietic stem cells, play a role in these clinical effects. These results suggest that Kampo Japanese herbal medicines are useful for anemia therapy.

Effects of Kampo Medicine Extracts on Morphological Changes in the Small Intestinal Mucosa of Mice with Age / 日本東洋医学雑誌

The effects of Rikkunshi-to (Liu jun zi tang), Hochu-ekki-to (Bu zhong yi qi tang), and Hange-shashin-to (Ban xia xie xin tang) on morphological changes in the small intestinal mucosa of mice with age were observed. The results indicated that Rikkunshi-to and Hochu-ekki-to had a beneficial effect on intestinal mucosal changes in 36-weeks-old mice. In particular, the improvement of the absorptive area of the intestinal villi and microvilli depending on the concentration of medicine was found. Ninjin-yoei-to had a strong effect on aged mice of 50 and 70 weeks. The morphology and absorptive function were significantly improved.