The herbal composition GGEx18 from Laminaria japonica, Rheum palmatum , and Ephedra sinica reduces obesity via skeletal muscle AMPK and PPARα

Department of Formula Sciences, College of Oriental Medicine, Dongeui University, Busan 614-052.
Pharmaceutical Biology (Impact Factor: 1.24). 12/2011; 50(4):506-15. DOI: 10.3109/13880209.2011.618502
Source: PubMed


Since AMP-activated protein kinase (AMPK) activation in skeletal muscle of obese rodents stimulates fatty acid oxidation, it is reasonable to hypothesize that pharmacological activation of AMPK might be of therapeutic benefit in obesity.
To investigate the effects of the traditional Korean anti-obesity drug GGEx18, a mixture of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), on obesity and the involvement of AMPK in this process.
After high fat diet-induced obese mice were treated with GGEx18, we studied the effects of GGEx18 on body weight, fat mass, skeletal muscle lipid accumulation, and the expressions of AMPK, peroxisome proliferator-activated receptor ά (PPARα), and PPARα target genes. The effects of GGEx18 and/or the AMPK inhibitor compound C on lipid accumulation and expression of the above genes were measured in C2C12 skeletal muscle cells.
Administration of GGEx18 to obese mice for 9 weeks significantly (p < 0.05) decreased body and adipose tissue weights compared with obese control mice (p < 0.05). Lipid accumulation in skeletal muscle was inhibited by GGEx18. GGEx18 significantly (p < 0.05) increased skeletal muscle mRNA levels of AMPKα1 and AMPKα2 as well as PPARα and its target genes. Consistent with the in vivo data, GGEx18 inhibited lipid accumulation, and similar activation of genes was observed in GGEx18-treated C2C12 cells. However, compound C inhibited these effects in C2C12 cells.
These results suggest that GGEx18 improves obesity through skeletal muscle AMPK and AMPK-stimulated expression of PPARα and its target enzymes for fatty acid oxidation.

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    ABSTRACT: Context: The activation of peroxisome proliferator-activated receptor α (PPARα) target genes promotes hepatic oxidation of fatty acids. We hypothesized that Gyeongshingangjeehwan 18 (GGEx18), a mixture of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), can regulate high-fat diet-induced hepatic steatosis through PPARα activation in the liver. Objective: To investigate the effects of GGEx18 on obesity-related hepatic steatosis and the responsible mechanism. Materials and methods: The effects of GGEx18 on hepatic lipid accumulation, serum lipid profiles, and the expression of PPARα target genes were studied in high-fat diet-induced obese mice. The effects of GGEx18 on the expression of the PPARα targets and PPARα reporter gene activation were measured in NMu2Li liver cells. Results: GGEx18 administration to obese mice for 9 weeks markedly (p < 0.05) decreased hepatic lipid accumulation compared with that in obese control mice. Serum triglyceride and total cholesterol levels were significantly (p <0.05) decreased by GGEx18. GGEx18 treatment increased the messenger RNA levels of PPARα target genes, which are responsible for fatty acid oxidation, in liver tissues. Consistent with the in vivo data, similar activation of genes was observed in GGEx18-treated NMu2Li liver cells. GGEx18 also elevated PPARα reporter gene expression in NMu2Li cells. Discussion and conclusion: These results suggest that GGEx18 prevents hepatic steatosis and hyperlipidemia in high-fat diet-induced obese mice, and this process may be mediated through PPARα activation in the liver.
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    ABSTRACT: The adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway arose early during evolution of eukaryotic cells, when it appears to have been involved in the response to glucose starvation and perhaps also in monitoring the output of the newly acquired mitochondria. Due to the advent of hormonal regulation of glucose homeostasis, glucose starvation is a less frequent event for mammalian cells than for single-celled eukaryotes. Nevertheless, the AMPK system has been preserved in mammals where, by monitoring cellular AMP:adenosine triphosphate (ATP) and adenosine diphosphate (ADP):ATP ratios and balancing the rates of catabolism and ATP consumption, it maintains energy homeostasis at a cell-autonomous level. In addition, hormones involved in maintaining energy balance at the whole-body level interact with AMPK in the hypothalamus. AMPK is activated by two widely used clinical drugs, metformin and aspirin, and also by many natural products of plants that are either derived from traditional medicines or are promoted as "nutraceuticals." Expected final online publication date for the Annual Review of Nutrition Volume 34 is July 17, 2014. Please see for revised estimates.
    No preview · Article · Sep 2012 · Annual Review of Nutrition
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    ABSTRACT: Objectives : This study was conducted to investigate the anti-obesity effects of mixed water extract of Plantaginis Semen & Poria (CJB) on obese rats induced with high fat diet. Method: Male Sprague-Dawley rats were divided into three groups; Normal group, high-fat (HF) group, HF+CJB(100 mg/kg, P.O.) for 8 weeks. The body weight, food intake and weights of adipose tissues were measured, respectively. Lipid profiles in serum were analyzed by automatic analyzer of blood. Obese marker proteins and the changes of NPY and LR immunoreactivities in hypothalamus were analyzed by Western blot and immunohistochemistry. Results : CJB significantly reduced body weight, food intake, adipose tissue weights compared to HF group. Serum triglyceride and total cholesterol were significantly higher in HF group than in Normal group however, CJB significantly lowered those of HF group. HDL-cholesterol level in CJB groups was elevated compared to HF group. The pAMPK in hypothalamus were decreased in that of HF group and that of CJB group decreased. Inversely, ACC was increased in HF group and that of CJB groups decrease. Expression of in hypothalamus was increased by CJB treatment. However, levels in CJB group were decreased compared to HF group. The expressions of NPY and LR in PVN and ARC of hypothalamus were decreased in CJB group, respectively. Conclusion : Administration of CJB can play anti-obesity through regulations of NPY and LR activities and obesity marker proteins in obese rat's hypothalamus.
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