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.