title: The Herbal Medicine KBH-1 Inhibits Fat Accumulation in 3T3-L1 Adipocytes and Reduces High Fat Diet-Induced Obesity through Regulation of the AMPK Pathway.
abstract: The aim of this study was to investigate whether a novel formulation of an herbal extract, KBH-1, has an inhibitory effect on obesity. To determine its anti-obesity effects and its underlying mechanism, we performed anti-obesity-related experiments in vitro and in vivo. 3T3-L1 preadipocytes were analyzed for lipid accumulation as well as the protein and gene expression of molecular targets involved in fatty acid synthesis. To determine whether KBH-1 oral administration results in a reduction in high-fat diet (HFD)-induced obesity, we examined five groups (n = 9) of C57BL/6 mice as follows: 10% kcal fat diet-fed mice (ND), 60% kcal fat diet-fed mice (HFD), HFD-fed mice treated with orlistat (tetrahydrolipstatin, marketed under the trade name Xenical), HFD-fed mice treated with 150 mg/kg KBH-1 (KBH-1 150) and HFD-fed mice treated with 300 mg/kg KBH-1 (KBH-1 300). During adipogenesis of 3T3-L1 cells in vitro, KBH-1 significantly reduced lipid accumulation and down-regulated the expression of master adipogenic transcription factors, including CCAAT/enhancer binding protein (C/EBP) β, C/EBP α and peroxisome proliferation-activity receptor (PPAR) γ, which led to the suppression of the expression of several adipocyte-specific genes and proteins. KBH-1 also markedly phosphorylated the adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, KBH-1-induced the inhibition effect on lipid accumulation and AMPK-mediated signal activation were decreased by blocking AMPK phosphorylation using AMPK siRNA. Furthermore, daily oral administration of KBH-1 resulted in dose-dependent decreases in body weight, fat pad mass and fat tissue size without systemic toxicity. These results suggest that KBH-1 inhibits lipid accumulation by down-regulating the major transcription factors of the adipogenesis pathway by regulating the AMPK pathway in 3T3-L1 adipocytes and in mice with HFD-induced obesity. These results implicate KBH-1, a safe herbal extract, as a potential anti-obesity therapeutic agent.
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea.|College of Pharmacy, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Lee
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea.
authors.forename: Taesoo
authors.initials: T
authors.lastname: Kim
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea.
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea.
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Nutraceutical Food R&D center, Kolmar BNH, 22-15 Sandan-gil, Jeonui-myeon, Sejong, 339-851, Republic of Korea.
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Nutraceutical Food R&D center, Kolmar BNH, 22-15 Sandan-gil, Jeonui-myeon, Sejong, 339-851, Republic of Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Yun
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea.
authors.forename: Jongwook
authors.initials: J
authors.lastname: Jeon
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, 305-764, Republic of Korea.
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.affiliation: KM Application Center, Korea Institute of Oriental Medicine, Daejeon, 305-811, Republic of Korea.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D029001:Herbal Medicine; D008297:Male; D051379:Mice; D009765:Obesity / Q000188:drug therapy*; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase