The Kampo Medicines Orengedokuto, Bofutsushosan and Boiogito Have Different Activities to Regulate Gene Expressions in Differentiated Rat White Adipocytes : Comprehensive Analysis of Genetic Profiles(Highlighted paper selected by Editor-in-chief, Pharmaco

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• Three Kampo medicines, Boiogito (BOT), Bofutsushosan (BTS) and Orengedokuto (OGT), used for obese patients were investigated for their effects on adipogenesis in cultured rat white adipocytes. Administration of the three extracts suppressed adipogenesis in concentration-dependent manners (1-100μg/ml) without any cytotoxicity. Changes in mRNA expression levels were analyzed using a Rat 230 2.0 Affymetrix GeneChip[○!R] microarray system. DNA microarray analysis (total probe set: 31099) using cDNAs prepared from adipocytes revealed that BOT, BTS and OGT increased the expression of 133-150 genes and decreased the expression of 42-110 genes by≥2-fold. We identified 329 downregulated genes and 189 upregulated genes among a total set of 514 probes (overlap: 4). Overall, genes related to cellular movement, cell death, cell growth/differentiation and immune responses were the most downregulated, while those related to lipid metabolism and cell signaling were the most upregulated. Semiquantitative reverse transcriptase-polymerase chain reaction (RT PCR) assays were conducted to confirm the microarray results. Analysis of the clustering profiles of the microarray results revealed that BOT and BTS changed the expression levels of similar genes mainly involved in small molecule biochemistry and cell differentiation, while OGT altered 10 genes related to lipid metabolism, in contrast to the effects of BOT and BTS. We also measured mRNA expression levels of seven selected genes highly contributing to the lipid metabolism by using semiquantitative RT PCR assay, that were acetyl-Coenzyme A carboxylase alpha (ACACA), AE binding protein 1 (AEBP1), patatin-like phospholipase domain containing 8 (PNPLA8), secretoglobin (SCGB1A1), adrenergic (ADRB3), adiponectin (ADIPOQ), monoglyceride lipase (MGLL). Beta-actin (ACTB) gene was used as an endogenous internal standard. The present findings indicate that these three herbal extracts have the potential to prevent adipogenesis in rat white adipocytes through different mechanisms via modulation of gene expression levels.

• 2008-11-01

著者

• YAMAKAWA Jun-ichi

  Department of General Medicine, Kanazawa Medical University

• ISHIGAKI Yasuhito

  Division of Core Facility of Medical Research Institute, Kanazawa Medical University

• TAKANO Fumihide

  Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science an

• TAKAHASHI Takashi

  Department of General Medicine, Kanazawa Medical University

• YOSHIDA Junko

  Department of Pharmacology, Kanazawa Medical University

• MORIYA Junji

  Department of General Medicine, Kanazawa Medical University

• TAKATA Takanobu

  Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science an

• TATSUNO Takanori

  Department of Pharmacognosy and Chemistry of Natural Products, Graduate School of Natural Science an

• SASAKI Kenroh

  Department of Pharmacognosy, Tohoku Pharmaceutical University

• OHTA Tomihisa

  Division of Core Facility of Medical Research Institute, Kanazawa Medical University

• TAKEGAMI Tsutomu

  Division of Molecular Oncology and Virology, Medical Research Institute, Kanazawa Medical University

• YOSHIZAKI Fumihiko

  Department of Pharmacognosy, Tohoku Pharmaceutical University

• 守屋 純二

  金沢医科大学 総合内科学

• Moriya Junji

  Department Of General Medicine Kanazawa Medical University

• Moriya Junji

  Department Of Cardiovascular Medicine National Cardiovascular Center

• Tatsuno Takanori

  Dep. Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Sci. And Technol.

• Ishigaki Yasuhito

  Div. Of Core Facility Medical Res. Inst. Kanazawa Medical Univ.

• Ishigaki Yasuhito

  金沢大学 自然科学研究科天然物化学

• Ishigaki Yasuhito

  Division Of Core Facility Medical Research Institute Kanazawa Medical University

• Takano Fumihide

  Dep. Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Sci. And Technol.

• Takano Fumihide

  Kanazawa Univ. Kanazawa Jpn

• Yoshizaki Fumihiko

  金沢医科大学 総合内科学

• Yoshizaki F

  Department Of Pharmacognosy Tohoku Pharmaceutical University

• Yamakawa Jun'ichi

  Department Of General Medicine Kanazawa Medical University

• Yamakawa Jun-ichi

  Department Of General Medicine Kanazawa Medical University:department Of Pharmacognosy Tohoku Pharma

• Yoshida Junko

  Department Of Obstetrics And Gynecology Shinshu University School Of Medicine

• OHTA Tomihisa

  Kanazawa University

• Ohta Tomihisa

  Kanazawa Univ. Kanazawa Jpn

• Ohta Tomihisa

  Dep. Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Sci. And Technol.

• Sasaki Kenroh

  Department Of Pharmacognosy Tohoku Pharmaceutical University

• Takahashi Takashi

  Department Of Applied Chemistry Tokyo Institute Of Technology

• Yoshizaki Fumihiko

  Department Of Pharmacognosy Tohoku Pharmaceutical University

• Takano Fumihide

  Department Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Science And

• Takegami Tsutomu

  Division Of Molecular Oncology And Virology Medical Research Institute

• Tanaka Tomoaki

  Department Of Pharmacognosy And Chemistry Of Natural Products Graduate School Of Natural Science And

• Takahashi Takashi

  Department Of Applied Chemistry Graduate School Of Science And Engineering Tokyo Institute Of Techno

• Takata Takanobu

  Division Of Molecular Oncology And Virology Medical Research Institute Kanazawa Medical University

• Nakaya Naoki

  Department Of Medical Oncology Kanazawa Medical University

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