Studies for the detail mechanisms of depression onset and the development of novel antidepressants based on "the Wakan-yaku, Sino-Japanese traditional medicine, theory"

以“和官、中日传统医学理论”为基础，研究抑郁症发病的详细机制以及新型抗抑郁药的开发

• 批准号: 21249047
• 负责人: TOHDA Michihisa
• 金额: $ 26.46万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21249047/
• 关键词: 和漢薬; 統合薬理学; MRI; 病態モデル; 遺伝子発現; 機能性精神疾患; 3D-HPLC; テーラーメード医療; 薬物感受性; 病態モデル動物; ヒトによる実験; 中枢神経; 消化器系; 上行性神経; 補中益気湯; 脳基底部; 初代培養細胞; うつ病; セロトニン2C受容体; 学習性無気力動物; ツメガエル卵母細胞; BNIP-3; 十全大補湯; STAT3

The Wakan-yaku is systematized medical care that has been practiced for several hundred years in Japan. Based on the theories of Wakan-yaku and using various Wakan-yaku prescriptions for depression treatment, the experimental studies for 1) novel-classification of depressive disorders, 2) establishment of highly effective drug treatment including the Wakan-yaku prescriptions, and 3) to supply of novel basic knowledge for development of new antidepressants were carried out. The following results were obtained; Wakan-yaku effects in the brain of drug-sensitive/-insensitive human and depression-model mice by image analytical method (MRI), the integrated viewpoint of the action mechanism using the model animal, identification and the significance of genes which changes the expression by Wakan-yaku or the constitutions in cultured cells, and the bioassay of active compounds by using the combined methods of electrophysiological technique with 3D-HPLC analysis/purification.

Wakan-Yaku是一种系统化的医疗保健，在日本已经实行了几百年。本研究以Wakan-Yaku理论为基础，采用多种Wakan-Yaku方剂治疗抑郁症，开展了1)抑郁症的新分类，2)建立包括Wakan-Yaku方剂在内的高效药物治疗的实验研究，3)为抗抑郁新药的开发提供新的基础知识。采用图像分析方法(MRI)对药物敏感/不敏感的人和抑郁症模型小鼠脑内的Wakan-Yaku效应，利用模型动物对作用机制的综合观点，Wakan-Yaku改变培养细胞表达或成分的基因的鉴定和意义，以及电生理技术和3D-HPLC分析/纯化相结合的方法对活性化合物进行生物活性测定。

项目成果

γ-Mangostin as an antidepressant drug : evaluation by the in vitro assay systems highly responsive to antidepressant

γ-山竹素作为抗抑郁药：通过抗抑郁药高度敏感的体外测定系统进行评估

• 发表时间: 2010
• 作者: Tohda M.;他計3名
• 通讯作者: 他計3名

一過性脳虚血誘発のラット海馬グルタミン?酸遊離量増加に対する黄連解毒湯の作用

Orengedokuto 对短暂性脑缺血所致大鼠海马谷氨酰胺酸释放增加的影响

• 发表时间: 2010
• 作者: 堀仁美;他計5名
• 通讯作者: 他計5名

ラット大脳皮質初代培養細胞の培養日数に伴う各種mRNA発現量変化とそれへの5-HT2CR RNA editingの影響

原代培养大鼠大脑皮层细胞各种mRNA表达水平随培养天数的变化及5-HT2CR RNA编辑对其的影响

• 发表时间: 2010
• 作者: 東田道久;松本欣三
• 通讯作者: 松本欣三

γ-Mangostin increases serotonin 2A/2C, muscarinic, histamine and bradykinin receptor mRNA expression

γ-Mangostin 增加血清素 2A/2C、毒蕈碱、组胺和缓激肽受体 mRNA 表达

• 发表时间: 2011
• 期刊: J Ethnopharmacol
• 影响因子: 5.4
• 作者: Sukma M;Tohda M;Suksamran S;Tantisira B
• 通讯作者: Tantisira B

Enhanced expression of BCL2/adenovirus EIB 19-kDa-interacting protenin 3 mRNA, a candidate for intrinsic depression-related factor, and effects of imipramine in the frontal cortex of stressed mice.

BCL2/腺病毒 EIB 19-kDa 相互作用蛋白 3 mRNA（内在抑郁相关因子的候选者）表达增强，以及丙咪嗪对应激小鼠额叶皮层的影响。

• 发表时间: 2010
• 期刊: Biol.Pham.Bull. 33
• 作者: Tohda M;他計4名
• 通讯作者: 他計4名