Changes of peripheral lymphocyte population in patients with chronic hepatitis C treated with herbal medicine (Maoto) and IFN-β

We recently reported that the herbal medicine (Maoto) might have immunomodulatory effects when used in conjunction with IFN-β. In order to examine the relation between host immune reaction and virological effects upon treatment with Maoto and IFN-β, we monitored the changes in lymphocyte populations of peripheral blood by flow-cytometry. Twenty-five patients with chronic hepatitis C were enrolled in this study. They received a daily dose of 6 million units of IFN-β for 8 weeks. Maoto was given orally 4 times a day during the IFN-β administration, and we monitored the changes in lymphocyte populations of peripheral blood by flow-cytometry. Six patients were sustained virological responders (SR), 10 were transient responders (TR), and 9 were nonresponders (NR). The percentage of CD16^+CD56^+ lymphocyte populations was decreased in all groups between pretreatment and 4 weeks, but it was significantly increased in SR compared with TR and NR between 4 and 8 weeks. The percentage of HLADR^+CD8^+ lymphocyte populations was significantly increased in SR and TR compared with NR between pretreatment and 8 weeks. Our results suggested that monitoring of changes in peripheral CD16^+CD56^+ and HLADR^+CD8^+ lymphocyte populations could be useful to treat chronic hepatitis C with the combination therapy of Maoto and IFN-β. 我々は最近, 麻黄湯にはIFNβと併用療法時において免疫修飾作用があるのではないかと報告してきた。そこで今回我々は麻黄湯とIFNβ併用療法時における宿主の免疫反応とウイルス学的効果の関連性について検討する為に, フローサイトメトリー解析を用いて, 併用療法前後での末梢血リンパ球サブセットの変化について検討した。25名のC型慢性肝炎患者を対象として8週間の麻黄湯とIFNβの併用療法を行った。また麻黄湯はIFN投与中1日4回服用とした。ウイルス学的検討では, 6名が著効群(SR), 10名が一過性有効群(TR), 9名が無効群(NR)だった。CD16^+CD56^+陽性リンパ球数の比率は, 治療前と比較して, 4週後には3群ともその比率が低下したが, 4週から8週後では, SR群でTR群とNR群と比較して有意な上昇が認められた。またHLADR^+CD8^+リンパ球数の比率は治療前後においてSR群とTR群でNR群と比較して有意な上昇が認められた。我々の結果より, C型慢性肝炎に対する麻黄湯とIFNβ併用療法時において, CD16^+CD56^+, HLADR^+CD8^+リンパ球数の変化をモニタリングすることが有用である可能性が示唆された

The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation of CREB

Hachimijiogan (HJG) is a traditional herbal medicine that improves anxiety disorders in patients with dementia. In this study, we tested the hypothesis that HJG exerts neurotrophic factor-like effects to ameliorate memory impairment in Alzheimer disease (AD) model rats. First, we describe that HJG acts to induce neurite outgrowth in PC12 cells (a rat pheochromocytoma cell line) like nerve growth factor (NGF) in a concentration-dependent manner (3 μg/ml HJG, p < 0.05; 10–500 μg/ml HJG, p < 0.001). While six herbal constituents of HJG, Rehmannia root, Dioscorea rhizome, Rhizoma Alismatis, Poria sclerotium, Moutan bark, and Cinnamon bark, could induce neurite outgrowth effects, the effect was strongest with HJG (500 μg/ml). Second, we demonstrated that HJG-induced neurite outgrowth was blocked by an inhibitor of cAMP response element binding protein (CREB), KG-501 (10 μM, p < 0.001). Moreover, HJG was observed to induce CREB phosphorylation 20–90 min after treatment (20 min, 2.50 ± 0.58-fold) and CRE-mediated transcription in cultured PC12 cells (500 μg/ml, p < 0.01; 1000 μg/ml, p < 0.001). These results suggest a CREB-dependent mechanism underlies the neurotrophic effects of HJG. Finally, we examined improvements of memory impairment following HJG treatment using a Morris water maze in AD model animals (CI + Aβ rats). Repeated oral administration of HJG improved memory impairment (300 mg/kg, p < 0.05; 1000 mg/kg, p < 0.001) and induced CREB phosphorylation within the hippocampus (1000 mg/kg, p < 0.01). Together, our results suggest that HJG possesses neurotrophic effects similar to those of NGF, and can ameliorate cognitive dysfunction in a rat dementia model via CREB activation. Thus, HJG could potentially be a substitute for neurotrophic factors as a treatment for dementia