The antiinflammatory mechanism of Igongsan in mouse peritoneal macrophages via suppression of NF-κB/Caspase-1 activation.

UNLABELLED: Igongsan (IGS), which is an herbal prescription composed of five different herbs, Ginseng Radix (root of Panax ginseng, Araliaceae), Atractylodis Rhizoma Alba (rhizome of Atractylodes Macrocephala, Compositae), Poria Sclerotium (sclerotium of Poria cocos, Polyporaceae), Glycyrrhizae Radix et Rhizoma (root and rhizome of Glycyrrhiza uralensis, Leguminosae), and Citri Unshius Pericarpium (Peel of Citrus unshiu, Rutaceae), has been traditionally used in Korea to treat a variety of inflammatory diseases. In this study, we investigated to elucidate the mechanism responsible for IGS's antiinflammatory effect in mouse peritoneal macrophages. The findings demonstrate that IGS inhibited the production of inflammatory cytokine and prostaglandins E2 . IGS inhibited the enhanced levels of cyclooxygenase-2 and inducible NO synthase caused by lipopolysaccharide (LPS). Additionally, it was shown that the antiinflammatory effect of IGS is through regulating the activation of nuclear factor-kappa B and caspase-1 in LPS-stimulated mouse peritoneal macrophages. These results provide novel insights into the pharmacological actions of IGS as a potential candidate for development of new drugs to treat inflammatory diseases. DISCUSSION AND CONCLUSION: These results provide novel insights into the pharmacological actions of IGS as a potential candidate for development of new drugs to treat inflammatory diseases.

Chrysophanic Acid Suppresses Adipogenesis and Induces Thermogenesis by Activating AMP-Activated Protein Kinase Alpha In vivo and In vitro.

Chrysophanic acid (CA) is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Though several studies have indicated numerous features of CA, no study has yet reported the effect of CA on obesity. In this study, we tried to identify the anti-obesity effects of CA. By using 3T3-L1 adipocytes and primary cultured brown adipocytes as in vitro models, high-fat diet (HFD)-induced obese mice, and zebrafish as in vivo models, we determined the anti-obesity effects of CA. CA reduced weight gain in HFD-induced obese mice. They also decreased lipid accumulation and the expressions of adipogenesis factors including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in 3T3-L1 adipocytes. In addition, uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), the brown fat specific thermogenic genes, were up-regulated in brown adipocytes by CA treatment. Furthermore, when co-treated with Compound C, the AMP-activated protein kinase (AMPK) inhibitor, the action of CA on AMPKα was nullified in both types of adipocytes, indicating the multi-controlling effect of CA was partially via the AMPKα pathway. Given all together, these results indicate that CA can ameliorate obesity by controlling the adipogenic and thermogenic pathway at the same time. On these bases, we suggest the new potential of CA as an anti-obese pharmacotherapy.

Interaction of Veratrum nigrum with Panax ginseng against Obesity: A Sang-ban Relationship.

Obesity has become a major health threat in developed countries. However, current medications for obesity are limited because of their adverse effects. Interest in natural products for the treatment of obesity is thus rapidly growing. Korean Medicine (KM) is characterized by the wide use of herbal formulas. However, the combination rule of herbal formulas in KM lacks experimental evidence. According to Shennong's Classic of Materia Medica, the earliest book of herbal medicine, Veratrum nigrum (VN) has antagonistic features against Panax ginseng (PG), and the PG-VN pair is strictly forbidden. In this study, we have shown the effects of PG, VN, and their combination on obesity in high-fat (HF) diet-induced obese mice and in 3T3-L1 cells. PG, VN, and PG-VN combination significantly reduced weight gain and the fat pad weight in HF diet-induced obese mice. They also significantly decreased lipid accumulation and the expressions of two major adipogenesis factors, PPAR γ and C/EBP α , in 3T3-L1 cells. In addition, the PG-VN combination had synergistic effects compared with the mixture of extracts of PG and VN on inhibition of PPAR γ and C/EBP α expressions at lower doses. These results indicate a new potential anti-obese pharmacotherapy and also provide scientific evidence supporting the usage of herbal combinations instead of mixtures in KM.

Corni Fructus Containing Formulation Attenuates Weight Gain in Mice with Diet-Induced Obesity and Regulates Adipogenesis through AMPK.

Obesity is a metabolic disorder characterized by chronic inflammation and dyslipidemia and is a strong predictor for the development of hypertension, diabetes mellitus, and cardiovascular disease. This study examined the antiobesity effect of an ethanol extract of Corni Fructus containing formulation (CDAP), which is a combination of four natural components: Corni Fructus, Dioscoreae Rhizoma, Aurantii Fructus Immaturus, and Platycodonis Radix. The cellular lipid content in 3T3-L1 adipocytes was assessed by Oil Red O staining. Expressions of peroxisome proliferator-activated receptor- γ (PPAR- γ ), CCAAT/enhancer-binding protein- α (C/EBP- α ), and lipin-1 were determined by real-time RT-PCR. Western blot was used to determine the protein levels of PPAR- γ , C/EBP- α , and AMP-activated protein kinase- α (AMPK- α ). The CDAP extract suppressed the differentiation of 3T3-L1 adipocytes by downregulating cellular induction of PPAR- γ , C/EBP- α , and lipin-1. The CDAP extract also significantly upregulated phosphorylation of AMPK- α . An in vivo study showed that CDAP induced weight loss in mice with high-fat-diet-induced obesity. These results indicate that CDAP has a potent anti-obesity effect due to the inhibition of adipocyte differentiation and adipogenesis.