title: Inhibition of preadipocyte differentiation and lipid accumulation by Orengedokuto treatment of 3T3-L1 cultures.
abstract: Obesity is a major cause of metabolic syndrome and is due to an increase in the number and hypertrophy of adipocytes. Accordingly, inhibition of the differentiation and proliferation of adipocytes may be used in the treatment and prevention of metabolic syndrome. This study investigated the effects of 50 commonly used Kampo medicines on the differentiation of 3T3-L1 preadipocytes to search for a drug with an antiobesity effect. Kampo medicines were screened, and the strongest differentiation-inhibitory effect was noted with Orengedokuto. To explore the active ingredients in Orengedokuto, the effects of four crude drug components of Orengedokuto were investigated. It was found that the differentiation-inhibitory effect of Orengedokuto was accounted for by Coptidis rhizome and Phellodendri cortex. Furthermore, berberine, a principal ingredient common to Coptidis rhizome and Phellodendri cortex, showed a differentiation-inhibitory effect. The effect of berberine involves an inhibition of the mRNA and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). Moreover, berberine inhibited lipid accumulation in adipocytes. These findings suggest that an antiobesity effect could be a new indication for Orengedokuto and that its active ingredient is berberine, with a mechanism involving the inhibition of PPARγ and C/EBPα expression.
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Nobutomo
authors.initials: N
authors.lastname: Ikarashi
authors.forename: Masataka
authors.initials: M
authors.lastname: Tajima
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Toda
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Ito
authors.forename: Wataru
authors.initials: W
authors.lastname: Ochiai
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D039323:Coptis / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects*; D020835:Medicine, Kampo; D051379:Mice; D009765:Obesity / Q000378:metabolism / Q000517:prevention & control*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D032102:Phellodendron / Q000737:chemistry; D008517:Phytotherapy; D024301:Plant Bark; D012333:RNA, Messenger / Q000378:metabolism; D027343:Rhizome
chemical_list: D019440:Anti-Obesity Agents; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004365:Drugs, Chinese Herbal; D047495:PPAR gamma; D012333:RNA, Messenger; C061676:oren gedoku to; D001599:Berberine