BNIP-3: a novel candidate for an intrinsic depression-related factor found in NG108-15 cells treated with Hochu-ekki-to, a traditional oriental medicine, or typical antidepressants.
Wakan-yaku is a type of Japanese and Sino traditional, systematized medical care that has been practiced for hundreds of years. To search for novel intrinsic factors related to the action of antidepressants, we used Hochu-ekki-to (HET), a Wakan-yaku medicine with antidepressive effects. First, we verified the quality of the HET by three-dimensional high-performance liquid chromatography and a cytotoxicity check in NG108-15 cells. We performed a DNA microarray analysis of the gene expression in cells treated with 50 micro/ml HET for more than 20 days. HET enhanced the expression of 125 (2.9%) genes and decreased the expression of 255 (6.0%) genes among the 4277 genes that were tested. The concentration-dependent increase in the expression of BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP-3) mRNA was particularly remarkable. A concentration-dependent increase in the expression of BNIP-3 mRNA was also observed when cells were treated with imipramine, mianserin, or milnacipran. These results suggest that BNIP-3 is a candidate for an intrinsic factor related to antidepressive effects and that Wakan-yaku theory may be useful for the identification of other intrinsic functional molecules.
Tohda
Michihisa
M
Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, Sugitani, Toyama, Japan. mickey_tonma@yahoo.co.jp
Hayashi
Hisae
H
Sukma
Monrudee
M
Tanaka
Ken
K
D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003521:Cyclopropanes / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006825:Hybridomas; D007099:Imipramine / Q000494:pharmacology; D008518:Medicine, East Asian Traditional; D008565:Membrane Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008803:Mianserin / Q000494:pharmacology; D051379:Mice; D000078764:Milnacipran; D024101:Mitochondrial Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003521:Cyclopropanes; D004365:Drugs, Chinese Herbal; D007099:Imipramine; D008565:Membrane Proteins; D008803:Mianserin; D000078764:Milnacipran; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors; C508686:BNip3 protein, mouse; C402943:bu-zhong-yi-qi-tang