Anti-Obesity and Anti-Adipogenic Effects of Administration of Arginyl-Fructose-Enriched Jeju Barley (Hordeum vulgare L.) Extract in C57BL/6 Mice and in 3T3-L1 Preadipocytes Models.

In our previous study, we reported that arginyl-fructose (AF), one of the Amadori rearrangement compounds (ARCs) produced by the heat processing of Korean ginseng can reduce carbohydrate absorption by inhibiting intestinal carbohydrate hydrolyzing enzymes in both in vitro and in vivo animal models. This reduced absorption of carbohydrate might be helpful to control body weight gain due to excessive carbohydrate consumption and support induced calorie restriction. However, the weight management effect, except for the effect due to anti-hyperglycemic action, along with the potential mechanism of action have not yet been determined. Therefore, the efforts of this study are to investigate and understand the possible weight management effect and mechanism action of AF-enriched barley extracts (BEE). More specifically, the effect of BEE on lipid accumulation and adipogenic gene expression, body weight gain, body weight, plasma lipids, body fat mass, and lipid deposition were evaluated using C57BL/6 mice and 3T3-L1 preadipocytes models. The formation of lipid droplets in the 3T3-L1 treated with BEE (500 and 750 µg/mL) was significantly blocked (p < 0.05 and p < 0.01, respectively). Male C57BL/6 mice were fed a high-fat diet (30% fat) for 8 weeks with BEE (0.3 g/kg-body weight). Compared to the high fat diet control (HFD) group, the cells treated with BEE significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (CEBP/α), the mRNA expression of downstream lipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), and sterol regulatory element-binding protein 1c (SREBP-1c). Supplementation of BEE effectively lowered the body weight gain, visceral fat accumulation, and plasma lipid concentrations. Compared to the HFD group, BEE significantly suppressed body weight gain (16.06 ± 2.44 g vs. 9.40 ± 1.39 g, p < 0.01) and increased serum adiponectin levels, significantly, 1.6-folder higher than the control group. These results indicate that AF-enriched barley extracts may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

A Pharmacokinetic Study of Ephedrine and Pseudoephedrine after Oral Administration of Ojeok-San by Validated LC-MS/MS Method in Human Plasma.

A sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was developed and fully validated for the simultaneous determination of ephedrine and pseudoephedrine in human plasma after oral administration of the herbal prescription Ojeok-san (OJS); 2-phenylethylamine was used as the internal standard (IS). Both compounds presented a linear calibration curve (r2 ≥ 0.99) over a concentration range of 0.2-50 ng/mL. The developed method was fully validated in terms of selectivity, lower limit of quantitation, precision, accuracy, recovery, matrix effect, and stability, according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. This validated method was successfully applied for the pharmacokinetic assessment of ephedrine and pseudoephedrine in 20 healthy Korean volunteers administered OJS.

Anaphylaxis - Lessons learnt when East meets West.

The rapidly increasing prevalence of allergic disorders over the past 2 decades highlights the need to understand the epidemiology of anaphylaxis. In Europe, the United States, and Australia, the incidence of anaphylaxis is estimated to be between 60 and 950 cases per 100 000 population, with a lifetime prevalence of anaphylaxis of 0.05%-2%. The incidence appears to be increasing over time. Although the existing Asian literature is heterogeneous and limited by under-reporting, it also suggests a similar increasing trend in anaphylaxis incidence in Asia. Anaphylaxis triggers in Asia, such as the predominance of shellfish and wheat in older children and adolescents, differ from those seen in Western populations. Triggers unique to Asia such as traditional Chinese medications, galacto-oligosaccharides, and food delicacies have also been reported. Low usage of adrenaline as first-line treatment of anaphylaxis is evident across all countries and is particularly concerning. There is a need to establish prospective, standardized protocols for anaphylaxis data collection and reporting, to enhance the collective understanding of anaphylaxis and its burden, gaps in management and to identify areas for future research and intervention in each region. Understanding of the underlying reasons explaining the difference between East and West will facilitate future primary preventive strategies.

Chloroform extract of deer antler inhibits osteoclast differentiation and bone resorption.

It has been reported that deer antler extract has anti-bone resorptive activity in vivo. However, little is known about the cellular and molecular mechanism of this effect. In this study, we investigated the effects of deer antler extracts on osteoclast differentiation and bone-resorption in vitro. Chloroform extract (CE-C) of deer antler inhibited osteoclast differentiation in mouse bone marrow cultures stimulated by receptor activator of NF-kappaB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). CE-C suppressed the activation of extracellular signal-regulated kinase (ERK), protein kinase B (PKB/Akt) and inhibitor of kappa B (I-kappaB) by RANKL in osteoclast precursor cells. It also inhibited the bone resorptive activity of differentiated osteoclasts that was accompanied by disruption of actin rings and induction of the apoptosis. These results demonstrate deer antler extract may be a useful remedy for the treatment of bone-resorption diseases such as osteoporosis.

Murine model of buckwheat allergy by intragastric sensitization with fresh buckwheat flour extract.

Food allergies affect about 4% of the Korean population, and buckwheat allergy is one of the most severe food allergies in Korea. The purpose of the present study was to develop a murine model of IgE-mediated buckwheat hypersensitivity induced by intragastric sensitization. Young female C3H/HeJ mice were sensitized and challenged intragastricly with fresh buckwheat flour (1, 5, 25 mg/dose of proteins) mixed in cholera toxin, followed by intragastric challenge. Anaphylactic reactions, antigen-specific antibodies, splenocytes proliferation assays and cytokine productions were evaluated. Oral buckwheat challenges of sensitized mice provoked anaphylactic reactions such as severe scratch, perioral/periorbital swellings, or decreased activity. Reactions were associated with elevated levels of buckwheatspecific IgE antibodies. Splenocytes from buckwheat allergic mice exhibited significantly greater proliferative responses to buckwheat than non-allergic mice. Buckwheat-stimulated IL-4, IL-5, and INF-gamma productions were associated with elevated levels of buckwheat-specific IgE in sensitized mice. In this model, 1 mg and 5 mg dose of sensitization produced almost the same degree of Th2-directed immune response, however, a 25 mg dose showed blunted antibody responses. In conclusion, we developed IgE-mediated buckwheat allergy by intragastric sensitization and challenge, and this model could provide a good tool for future studies.

Genetically modified and wild soybeans: an immunologic comparison.

Most traits introduced into genetically engineered crops result from the expression of new proteins. As the first step toward assessing the allergenic potential of genetically modified organism (GMO) food, immunologic and physicochemical characterizations are needed. We prepared crude extract from GMO soybeans, wild soybeans, curd, and soy milk and then performed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). After acidification with HCl, the samples were separated to globulin and whey. To evaluate changes in protein composition, either the samples were heated or pepsin was added. Polymerase chain reaction with primer encoding the 35S-promotor and the 3-enol-pyruvyl-shikimat-5-phosphat-synthase gene were performed, respectively, to detect the GMO component. SDS-PAGE results showed definite protein bands at 80 kDa in GMO soybean, 50 kDa in wild soybean, and a similar distribution of protein bands was noticed below 40 kDa. It was difficult to observe protein distribution because of modifications that occurred during processing in soybean-processed products. After heating, proteins of GMO and wild soybeans showed similar distributions and no distinct bands were detected at 50 and 80 kDa. Although SDS-PAGE analyses of raw GMO and wild soybeans differed, the same protein bands of 68, 37, and 20 kDa were observed in the globulin fraction after acidification. After adding pepsin, 20- and 68-kDa bands were found preserved in GMO and wild soybeans. The polymerase chain reaction procedures with primers specific to GMO soybeans showed that GMO soybeans and some curd samples included a GMO component. The skin test results of 49 patients showed 13 positive results to wild soybeans and 8 positive results to GMO soybeans. One patient had a positive skin test result to GMO soybeans only. Sera from nine patients with positive skin tests to the crude extract and a positive capsulated allergen product test to the soybean antigen were used for the immunoblotting of GMO and wild soybeans. GMO soybeans revealed a unique strong immunoglobulin E binding band at 25 kDa in some patients and wild soybeans showed a strong immunoglobulin E binding band at 30-36 kDa. To assess the allergenicity of GMO food, more research, including a selection of controlled sample materials and immunoassays of qualified sera, is needed.

Vascular endothelial growth factor up-regulates expression of receptor activator of NF-kappa B (RANK) in endothelial cells. Concomitant increase of angiogenic responses to RANK ligand.

Vascular endothelial growth factor (VEGF) is known as a key regulator of angiogenesis during endochondral bone formation. Recently, we demonstrated that TNF-related activation-induced cytokine (TRANCE or RANKL), which is essential for bone remodeling, also had an angiogenic activity. Here we report that VEGF up-regulates expression of receptor activator of NF-kappa B (RANK) and increases angiogenic responses of endothelial cells to TRANCE. Treatment of human umbilical vein endothelial cells (HUVECs) with VEGF increased both RANK mRNA and surface protein expression. Although placenta growth factor specific to VEGF receptor-1 had no significant effect on RANK expression, inhibition of downstream signaling molecules of the VEGF receptor-2 (Flk-1/KDR) such as Src, phospholipase C, protein kinase C, and phosphatidylinositol 3'-kinase suppressed VEGF-stimulated RANK expression in HUVECs. Moreover, the MEK inhibitor PD98059 or expression of dominant negative MEK1 inhibited induction of RANK by VEGF but not the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM). VEGF potentiated TRANCE-induced ERK activation and tube formation via RANK up-regulation in HUVECs. Together, these results show that VEGF enhances RANK expression in endothelial cells through Flk-1/KDR-protein kinase C-ERK signaling pathway, suggesting that VEGF plays an important role in modulating the angiogenic action of TRANCE under physiological or pathological conditions.