HOX-7 suppresses body weight gain and adipogenesis-related gene expression in high-fat-diet-induced obese mice.

BACKGROUND: HOX-7 is a newly developed dietary formula composed of traditional oriental herbal medicines. The formula was developed with the aim of improving weight control. We investigated the anti-obesity effect of HOX-7 on high-fat-diet (HFD)-induced obesity in C57BL/6 mice. METHODS: The mice were divided into four groups and were fed a normal diet (ND), HFD, or HFD with oral administration of HOX-7 at 100 or 200 mg/kg/day for 12 weeks. Body and fat weight, histological changes of fat tissue, and the expression of key adipogenic transcription factors were investigated. RESULTS: The body weight of mice fed the HFD with HOX-7 was significantly decreased compared to the HFD group. There were no obvious differences in weekly food intake among the 4 groups. The weight of the epididymal and total fat pads was reduced in mice fed the HFD with HOX-7. Treatment with HOX-7 also substantially attenuated the expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein α, sterol regulatory element binding protein 1c, adipocyte P2, liver X receptor, and lipoprotein lipase in the epididymal adipose tissue. CONCLUSION: Overall, this study highlighted the anti-obesity effects of HOX-7, a finding that could contribute to the development of natural anti-obesity herbal medicines.

Protective effect of Sam-Hwang-Sa-Sim-Tang against hepatic steatosis in mice fed a high-cholesterol diet.

BACKGROUND: Sam-Hwang-Sa-Sim-Tang (SHSST) is a traditional Oriental medication that has been commonly used in Korea for the treatment of hypertension, insomnia, and chest pain. In addition, some studies reported that administration of SHSST results suppression of hyperlipidemia in rats or lowering lipid plasma level such as total cholesterol (TC). Those results made us find and demonstrate positive effect of SHSST much more. The aim of the current study was to examine whether SHSST exerts an effect against hepatic steatosis and two type of SHSST has different efficacy on liver steatosis. METHODS: Total 40 mice were divided randomly and equally into 4 groups: a normal diet (CON) group, high-cholesterol diet (HC) group, and treatment groups fed a high-cholesterol diet (HCD) with a 30% or 80% ethanol extract of SHSST (SHSST-L and SHSST-H, respectively). The HCD was given for 9 weeks. The SHSST-treated groups were orally administered SHSST at a dose of 150 mg/kg, whereas the other groups received physiological saline. RESULTS: SHSST administration to mice resulted in a decline in serum levels of total cholesterol and low-density lipoprotein. Histological examination showed that lipid droplets were smaller in the SHSST-treated group than in the HC group. At the protein level, expression of sterol regulatory element-binding protein 2 (SREBP-2) was suppressed by SHSST. In addition, the mRNA expression of cholesterol metabolism-related molecules such as SREBP-2, liver X receptor (LXR), low-density lipoprotein receptor (LDLR), and 3-hydroxy-3methylglutary-CoA (HMG-CoA) was also suppressed in SHSST-treated groups in the liver. In the aorta tissue, SHSST decreased the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), transforming growth factor (TGF)-ß1, and fibronectin. CONCLUSIONS: The present study indicates that SHSST protects against liver steatosis and protects vessels against inflammation arising from excessive ingestion of cholesterol. These findings may also suggest that SHSST could be used as an adjuvant remedy for protection against liver steatosis.

Anti-inflammatory effect of Acalypha australis L. via suppression of NF-κB signaling in LPS-stimulated RAW 264.7 macrophages and LPS-induced septic mice.

We evaluated the anti-inflammatory activity of methanol extracts of Chinese medicinal plants from Beijing and determined which extract was the most effective. We found the methanol extract of Acalypha australis L. (AAL) to be the most effective. AAL has been used for clearing heat, toxic material, and hemostasia in Chinese medicine. Although these uses are closely related to inflammation, the anti-inflammatory effect of AAL has not yet been described and its underlying mechanism remains unclear. Therefore, we aimed to identify anti-inflammatory effect of AAL and its underlying mechanism in vitro and in vivo. In RAW 264.7 macrophages, cytotoxicity was evaluated by MTT assay and nitric oxide (NO) was measured with Griess reagent. To confirm the production of pro-inflammatory cytokines and its mRNA expression, enzyme immunoassay (EIA) and quantitative real-time PCR (qRT-PCR) were performed. Further, protein expression was analyzed by western blotting. Septic shock was induced by intraperitoneal injection of LPS (25 mg/kg) in mice. One hour before LPS injection, AAL (25 and 50 mg/kg) was administered orally. In LPS-stimulated macrophages, AAL inhibited NO production at concentrations without cytotoxicity. Additionally, AAL reduced not only inducible nitric oxide synthase (iNOS) expression but the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by attenuating nuclear factor-kappa B (NF-κB)-related proteins (NF-κB p65, phosphorylation of inhibitor κB-α; p-IκB-α, phosphorylation of inhibitor κB kinase-α/ß; p-Ikk-α/ß). Moreover, AAL enhanced the survival rate of mice through the inhibition of iNOS expression and IL-6 and interleukin-1ß (IL-1ß) production in LPS-induced septic mice. Furthermore, AAL also reduced the expression of NF-κB-related proteins. These finding suggest that AAL is related to the modulation of inflammatory reactions by blocking NF-κB activation in LPS-stimulated RAW 264.7 macrophages and LPS-induced septic mice.

Inhibitory effects of bee venom on mast cell-mediated allergic inflammatory responses.

Although bee venom (BV) is a toxin that causes bee stings to be painful, it has been widely used clinically for the treatment of certain immune­associated diseases. BV has been used traditionally for the treatment of chronic inflammatory diseases. In this regard, the present study analyzed the effect of BV on the regulation of inflammatory mediator production by mast cells and their allergic inflammatory responses in an animal model. HMC­1 cells were treated with BV prior to stimulation with phorbol­12­myristate 13­acetate plus calcium ionophore A23187 (PMACI). The production of allergy­associated pro­inflammatory mediators was examined, and the underlying mechanisms were investigated. Furthermore, to investigate whether BV exhibits anti­inflammatory effects associated with anti­allergic effects in vivo, a compound 48/80­induced anaphylaxis model was used. BV inhibited histamine release, mRNA expression and production of cytokines in the PMACI­stimulated HMC­1 cells. Furthermore, the inhibitory effects of BV on mitogen­activated protein kinase (MAPK), MAPK kinase, signal transducer and activator of transcription 3 (STAT3) and Akt were demonstrated. The present study also investigated the ability of BV to inhibit compound 48/80­induced systemic anaphylaxis in vivo. BV protected the mice against compound 48/80­induced anaphylactic­associated mortality. Furthermore, BV suppressed the mRNA expression levels of pro­inflammatory cytokines, and suppressed the activation of MAPK and STAT3 in this model. These results provide novel insights into the possible role of BV as a modulator for mast cell­mediated allergic inflammatory disorders.

Liriopis tuber inhibit OVA-induced airway inflammation and bronchial hyperresponsiveness in murine model of asthma.

Liriope platyphylla is one of the well-known herb used in oriental medicine for treatment asthma and bronchial and lung inflammation. Anti-asthmatic effects of Liriope platyphylla in the development of OVA-induced airway inflammation and murine asthma model have not been fully investigated in vivo. Asthma is a chronic inflammatory disease of the mucosa and is associated with excess production of Th2 cytokines and eosinophil accumulation in lung. To clarify the anti-inflammatory and anti-asthmatic effects of Liriope platyphylla, we examined the influence of liriopis tuber (LRT) on the development of pulmonary eosinophilic inflammation in murine model of asthma. Our results have shown that LRT were demonstrated on the accumulation of eosinophills into airways, with reduction of eosinophil, total lung leukocytes numbers by reduction IL-5, IL-13, IL-4 and IgE levels in the BALF and serum. Moreover, LRT decreased eosinophil CCR3 expression and CD11b expression in lung cells. These results indicate that LRT has a deep inhibitory effects on airway inflammation and hyperresponsiveness in murine model of asthma and play an crucial role as a immunomodulator which possess anti-inflammatory and anti-asthmatic property by modulating the relationship between Th1/Th2 cytokine imbalance.

Molecular mechanisms underlying the anti-obesity potential of prunetin, an O-methylated isoflavone.

Prunetin is an O-methylated isoflavone, which is a type of flavonoid. There are a limited number of reports detailing the biological activities of prunetin. Although an anti-inflammatory effect of prunetin has been reported in vitro, to our knowledge, there have been no reports on anti-adipogenic effects of prunetin in obese animals. The aims of this study were to determine whether prunetin suppresses high-fat diet (HFD)-induced adipogenesis in the liver and visceral adipose tissues of mice, and to explore the underlying mechanisms mediating the actions of prunetin. To this end, mice were fed a HFD for 10 weeks to induce obesity, and prunetin (10 µg/kg or 20 µg/kg) was administered in the last 3 weeks. Compared to saline-treated mice, mice treated with prunetin showed significantly reduced body weight gain, visceral fat pad weights, and plasma glucose levels. We found that prunetin significantly inhibited the HFD-induced upregulation of the expression of important adipogenic genes (PPARγ, C/EBPα, SREBP, aP2, LPL adiponectin, and leptin), and suppressed HFD-mediated increase in expression of lipid metabolism-related genes (SREBP, PPARγ, LXR, and HMG-CoA) in the liver tissues. Furthermore, prunetin induced expression of adiponectin receptors 1 and 2 (adipoR1, adipoR2), as well as that of AMP-activated protein kinase (AMPK) in the liver and adipose tissue. These results suggest that prunetin mediates anti-obesity/adipogenesis effects by suppressing obesity-related transcription through a feedback mechanism that regulates the expression of adiponectin, adipoR1, adipoR2, and AMPK.