Anti-Obesity Effects of Ecklonia cava Extract in High-Fat Diet-Induced Obese Rats.

Obesity is becoming a global epidemic as a result of high-calorie food intake and unhealthy lifestyles. Different marine plants, especially brown algae (Ecklonia cava), are traditionally used to treat different health-related issues. The study was carried out to investigate the anti-obesity properties of E. cava 70% ethanol extract. To evaluate the anti-obesity effect of E. cava, both in vitro and in vivo tests were performed. E. cava suppresses pre-adipocyte 3T3-L1 differentiation in a dose-dependent manner. In HFD-induced obese rats' models, administration of E. cava 125, 250, and 500 mg/kg significantly decreases total body weight and organs, especially liver weight, in all treatment groups. Adipose tissue weight, including subcutaneous, epididymal, peritoneal, and mesenteric adipose tissue, was markedly reduced in E. cava-treated HFD rats in dose-dependent manners. In addition, liver-related biomarkers AST, ALP, ALT, and GGT were evaluated; the lower level of liver-related biomarkers indicates no liver injury or fatty liver issue in E. cava HFD treatment groups. In addition, E. cava treatment has significant effects on the expression of adipogenic and lipogenic (PPAR-γ, FAS, LPL, and SREBP-1c) genes. Altogether, these results show the anti-obesity effect of E. cava. We concluded that E. cava could be a potential candidate for the prevention of obesity-induced by a high-fat diet.

Antioxidant Effects of Bioactive Compounds Isolated from Pressurized Steam-Treated Corni Fructus and Their Protective Effects Against UVB-Irradiated HS68 Cells.

This study evaluated the antioxidant and protective effects of bioactive compounds isolated from pressurized steam-treated Corni Fructus (PSC). We had previously tested the protective effects of the furan fraction containing 5-hydroxymethylfurfural (5-HMF), polyphenol fraction containing gallic acid, and iridoid glycoside fraction containing morroniside and loganin. We measured the potency of antioxidant activities of the bioactive compounds isolated from PSC via oxygen radical absorbance capacity (ORAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays. One fraction in particular (named F-2) not only contained high amounts of phenolics but also had potent antioxidant activities. The protective effects of F-2 were evaluated by measuring the levels of the collagen-degrading enzyme, matrix metalloproteinase-1 (MMP-1), and the marker of collagen biosynthesis, procollagen type I C-peptide (PIP), in UVB-treated HS68 fibroblasts. MMP-1 levels decreased in an F-2 concentration-dependent manner, and PIP secretion from the cultured HS68 cells was significantly higher than that from the UVB-irradiated cultures alone. Further, F-2 attenuated UVB-induced MMP-1 and ameliorated UVB-downregulated collagen type I alpha 1 mRNA expression in HS68 cells. Therefore, F-2 isolated from PSC is a good candidate for the prevention of skin damage from free radicals in various skin conditions.

Modulation of lipid metabolism by polyphenol-rich grape skin extract improves liver steatosis and adiposity in high fat fed mice.

This study investigated the influence of polyphenol-rich grape skin extract (GSE) on adiposity and hepatic steatosis in mice fed a high fat diet (HFD) and its underlying mechanisms based on adipose and hepatic lipid metabolism. C57BL/6J mice were fed a normal diet or a HFD (20% fat, w/w) with or without GSE (0.15%, w/w) for 10 weeks. The supplementation of GSE significantly lowered body weight, fat weight, plasma free fatty acid level, and hepatic lipid accumulation compared to the HFD group. Plasma leptin level was significantly lower, while the plasma adiponectin level was higher in the GSE group than in the HFD group. GSE supplementation significantly suppressed the activities of lipogenic enzymes in both adipose and liver tissues, which was concomitant with ß-oxidation activation. Furthermore, GSE reversed the HFD-induced changes of the expression of genes involved in lipogenesis and ß-oxidation in the liver. These findings suggest that GSE may protect against diet-induced adiposity and hepatic steatosis by regulating mRNA expression and/or activities of enzymes that regulate lipogenesis and fatty acid oxidation in the adipose tissue and liver.

Grape skin extract reduces adipogenesis- and lipogenesis-related gene expression in 3T3-L1 adipocytes through the peroxisome proliferator-activated receptor-γ signaling pathway.

We previously reported that grape skin ethanol extract (GSE) decreases adipogenic transcription factor gene expression, inhibiting triglyceride accumulation in 3T3-L1 adipocytes. In this study, we hypothesized that GSE may induce differential expression profiles in adipocytes, thus providing protection against obesity. Thirty-five genes involved in the peroxisome proliferator-activated receptor-γ (PPARγ) signaling pathway, lipid metabolism, or adipogenesis were identified through microarray analysis of adipocytes treated with GSE. Expression of the genes involved in PPARγ signaling, Adipoq, Scd1, Nr1h3, Fabp5, Scd2, and Pparg decreased with GSE treatment, whereas expression of Ppargc1a increased. Lipid metabolism-associated genes Mlxp1, Stat5a, Hsl, Plin1, and Vdr were down-regulated. Interestingly, GSE also affected expression of genes related to the mitogen-activated protein kinases pathway. GSE extract treatment decreased expression of aP2, Fas, and Tnfa, known markers of adipogenesis, as measured by real-time polymerase reaction. These findings demonstrate the antiadipogenic effects of GSE on 3T3-L1 adipocytes at the genetic level, primarily on the PPARγ signaling pathway.

Grape skin and loquat leaf extracts and acai puree have potent anti-atherosclerotic and anti-diabetic activity in vitro and in vivo in hypercholesterolemic zebrafish.

Three major sources of flavonoids and phenolic compounds, which are commonly used in food industry, namely loquat leaf (LL), grape skin (GS) and acai puree, were tested in regard to their potential anti-atherosclerotic and anti-diabetic activity. The compounds were evaluated by in vitro antioxidant assay using a macrophage model and for in vivo hypolipidemic activity using zebrafish. In assays in vitro, all extracts demonstrated potent ferric ion reductive capacity, radical-scavenging activity and inhibition of low-density lipoprotein (LDL) oxidation at a final concentration of 0.1 mg/ml. Extracts could also abrogate fructose-mediated protein glycation and mildly inhibit cholesteryl ester transfer protein (CETP). Cellular uptake of oxidized or acetylated LDL into macrophages was inhibited by acai treatment (final concentration, 0.1 mg/ml) and moderately diminished by GS and LL extracts. After 4 weeks of feeding on a high cholesterol diet (HCD), zebrafish exhibited serum total cholesterol (TC) and triglyceride (TG) levels 2.5-fold higher than those fed a normal diet (ND). Within the experimental group, those fed acai demonstrated the lowest serum TC and CETP activity, while the LL-consuming group showed a reduction in serum TC and TG relative to HCD-fed fish. Serum glucose levels also increased in the HCD group, to threefold above the ND group; GS and LL feeding elicited the greatest reduction in hyperglycemia. The groups consuming acai and LL showed much less hepatic inflammation, as well as attenuation of fatty liver and a reduced content of oxidized species. In conclusion, extracts of LL, GS, and acai shared antioxidant, anti-inflammatory and anti-atherosclerotic activity in cellular assays and in a hypercholesterolemic zebrafish model.

Turmeric and laurel aqueous extracts exhibit in vitro anti-atherosclerotic activity and in vivo hypolipidemic effects in a zebrafish model.

Culinary herbs and spices have been widely used for their hypoglycemic, lipid-lowering, and anti-inflammatory activities. This study examined the physiologic activity of hydrophilic components using extracts of turmeric or laurel leaf powder. Aqueous extracts of turmeric and laurel showed potent inhibitory activity against fructose-mediated glycation with antioxidant ability against low-density lipoprotein (LDL) oxidation and radical scavenging activity. The turmeric and laurel extracts had potent cholesteryl ester transfer protein (CETP) inhibitory ability (up to 23% and 40% inhibition, respectively) at a final concentration of 10 µg/mL. The turmeric and laurel extracts inhibited the cellular uptake of oxidized LDL into macrophages, which is the initial step in atherogenesis. For in vivo testing, zebrafish consumed a high cholesterol diet (HCD) (final concentration, 4% [wt/wt]) with or without turmeric or laurel powder (final concentration, 10% [wt/wt]). The turmeric and laurel groups had a 14% and 12% decrease, respectively, in the weight and height ratios compared to the HCD group. The plasma total cholesterol level was significantly lower in the turmeric and laurel groups (48% and 28% less, respectively, than in the HCD group). Plasma triglycerides were more markedly reduced in the turmeric and laurel groups than in the HCD group (68% and 56% less, respectively, than the HCD group). In conclusion, the hydrophilic extracts of turmeric and laurel potently suppressed the incidence of atherosclerosis via a strong antioxidant potential, prevention of apolipoprotein A-I glycation and LDL phagocytosis, and inhibition of CETP. Consumption of turmeric and laurel extracts exhibited hypolipidemic and antioxidant activities in a hypercholesterolemic zebrafish model.

The butanol fraction of Eclipta prostrata (Linn) increases the formation of brain acetylcholine and decreases oxidative stress in the brain and serum of cesarean-derived rats.

Eclipta prostrata has been used as a traditional medicinal plant to prevent dementia and to enhance memory in Asia. Its potential as a nootropic and as an antioxidant have been reported in mice. We hypothesized that Eclipta may affect the formation of neurotransmitters and the inhibition of oxidative stress. Charles River cesarean-derived rats (male, 180 ± 10 g) were fed experimental diets supplemented with 0 mg (control), 25 mg (E25), 50 mg (E50), or 100 mg (E100) of a freeze-dried butanol fraction of E prostrata per kilogram of diet for 6 weeks. The acetylcholine level was significantly increased by 9.6% and 12.1% in the brains of E50 and E100 groups, respectively, as compared with the control group that was fed standard diet alone. The acetylcholine esterase activity was significantly increased by 13.1% and 19.7% in the brains of E50 and E100 groups, respectively, compared with the control group. Monoamine oxidase-B activity was significantly decreased by 10.5% in the brains of the E100 group, and the superoxide radical level was significantly reduced by 9.4% in the serum of the E100 group compared with the control group. Superoxide dismutase activity was significantly increased by 9.6% and 11.6% in the serum of E50 and E100 groups, respectively, compared with the control group. These results clearly demonstrate the effects of E prostrata on the formation of acetylcholine in the brain and the inhibition of oxidative stress in the brain and serum of rats. These findings may have implications for preventing dementia and enhancing memory function in humans.

Inhibitory effects of Bulnesia sarmienti aqueous extract on agonist-induced platelet activation and thrombus formation involves mitogen-activated protein kinases.

ETHNOPHARMACOLOGICAL RELEVANCE: B. sarmienti has long been recognized in folk medicine as a medicinal plant with various medicinal uses. Traditionally, it has been appreciated for the skin-healing properties of its essence. The bark has also been employed to treat stomach and cardiovascular disorders and reported to have antitumor, antioxidant and anti-inflammatory activities. However, information on its antiplatelet activity is limited. AIM OF THE STUDY: To examined the effects of B. sarmienti aqueous extract (BSAE) in platelet physiology. MATERIALS AND METHODS: The anti-platelet activity of BSAE was studied using rat platelets for in vitro determination of the extract effect on agonist-induced platelet aggregation, ATP secretion, [Ca(2+)](i) mobilization and MAP kinase phosphorylation. The extract in vivo effects was also examined in arterio-venous shunt thrombus formation in rats, and tail bleeding time in mice. RESULT: HPLC chromatographic analysis revealed that B. sarmienti extract contained (+)-catechin (C), (-)-epigallocatechin (EGC), (-)-epicatechin (EC), and (-)-epicatechin gallate (ECG). BSAE, significantly and dose dependently, inhibited collagen, thrombin, or ADP-induced platelet aggregation. The 50 percent inhibitory concentrations (IC(50)) of the extract for collagen, thrombin and ADP-induced platelet aggregation were 45.3+/-2.6, 100+/-5.6 and 110+/-4.6 microg/ml, respectively. Collagen activated ATP release and thrombin-induced intracellular Ca(2+) concentration were reduced in BSAE-treated platelets. In addition, the extract in vivo activity showed that BSAE at 100 mg/kg significantly attenuated thrombus formation in rat extracorporeal shunt model while mice tail bleeding time was not affected. Moreover, BSAE attenuated p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase 1 (JNK1) and extracellular-signal-regulated protein kinase 2 (ERK2) phosphorylations. CONCLUSION: BSAE inhibits platelet activation, granule secretion, aggregation, and thrombus formation without affecting bleeding time, and that this effect is mediated by inhibition of P38, JNK1 and ERK2 phosphorylations. The ability of BSAE to inhibit platelet function might be relevant in cases involving aberrant platelet activation where the plant extract could be considered as a candidate to anti-platelet and antithrombotic agent.

Monoacylglycerol (MAG)-oleic acid has stronger antioxidant, anti-atherosclerotic, and protein glycation inhibitory activities than MAG-palmitic acid.

A functional oil containing diacylglycerol (DAG) and monoacylglycerol (MAG) has been shown to have a strong anti-atherosclerotic effect in a mouse model. Among the lipid components, MAG is responsible for the beneficial effect with an enhanced antioxidant effect in the mouse model. In this report, several MAG-containing fatty acids (MAG-oleic acid [MAG-O], MAG-palmitic acid [MAG-P], and MAG-stearic acid [MAG-S]) were synthesized, and the antioxidant and anti-atherogenic activities were evaluated in vitro and in a cellular model. MAG-O had the strongest radical scavenging and antioxidant activities against copper-mediated low-density lipoprotein (LDL) oxidation and the strongest inhibitory activity against LDL-associated phospholipase A(2) and exhibited potent activation of paraoxonase activity, which contributes to the maintenance of antioxidant activity. All MAG species in this study exhibited inhibitory activity against glycation of apolipoproteins, in contrast to DAG. Oxidized LDL uptake into THP-1 cells was strongly inhibited by MAG-O treatment at a final concentration of 20 microM. MAG-O-treated cell culture medium showed the lowest production of malondialdehyde and lipid hydroperoxide compared to MAG-S and MAG-P. In conclusion, MAG-O had potent antioxidant, antidiabetic, and anti-atherogenic effects in vitro and in a cellular model.

Mechanism of macrophage activation induced by beta-glucan produced from Paenibacillus polymyxa JB115.

Beta-glucans are heterogeneous groups of glucose polymers found in the cell walls of fungi, plants and some bacteria. Our previous report showed that a novel beta-1,3/1,6-glucan produced from Paenibacillus (P.) polymyxa JB115 can induce nitric oxide (NO) production in RAW264.7 cells. In the present study, the beta-glucan significantly increased luciferase activity in cells transfected with NFkappaB or AP1, but not STAT1, reporter vector DNA, which contain their binding promoter site. All specific NFkappaB and MAPKs pathway inhibitors (pyrrolidine dithiocarbamate, AG490, U0126, SB203580 and SP600125) remarkably attenuated NO production induced by the beta-glucan. Furthermore, Western blot analysis revealed that the stimulation of Raw264.7 cells by beta-glucan induced phosphorylation of IkappaB and the consequent translocation of NFkappaB into the nucleus. Meanwhile, phosphorylation of ERK1/2, JNK/SAPK and p38 MAPKs in cytoplasm were also confirmed. All these results indicated that beta-glucan from P. polymyxa JB115 activates macrophages through MAPKs and NFkappaB signaling pathway.

The functional and compositional properties of lipoproteins are altered in patients with metabolic syndrome with increased cholesteryl ester transfer protein activity.

To compare the molecular composition and functional differences at the lipoprotein level, we analyzed individual lipoprotein fractions from male patients with metabolic syndrome (MetS) (n=10) and gender- and age-matched healthy controls (n=14). The MetS group had significantly higher obesity, blood pressure, serum cholesterol, triglyceride (TG), adiponectin, and uric acid levels than the control group, while the serum blood urea nitrogen and creatinine levels of the MetS group were in the normal range. The MetS group had much weaker serum antioxidant ability and were more susceptible to copper-mediated low-density lipoprotein (LDL)-oxidation. TG and apoC-III co-accumulated with LDL, high density lipoprotein (HDL)2, and HDL3 in the MetS group. The MetS group had serum amyloid A (SAA)-enriched HDL2 and HDL3, although the serum level of SAA was not higher than in controls. The MetS group had significantly deprived paraoxonase (PON) activity in the serum and HDL, while the MetS group had 38% higher serum cholesteryl ester transfer protein (CETP) activity than that of the control group. Many serum parameters, such as TG, apoC-III, and uric acid, were elevated in the MetS group, and most of these measures were enriched in the LDL and HDL fractions rather than the very low density lipoprotein (VLDL) fraction. The lipid and apolipoprotein composition of HDL was severely altered and its beneficial functions were severely diminished. ApoA-I level was more readily detected in lipoprotein-deficient serum of the MetS group, indicating that the apoA-I exists in a lipid-free state. These results suggest that the MetS group had dysfunctional HDL that enriched TG, apoC-III, CETP, and SAA without antioxidant activity.

Growth-inhibitory effects of a Bulnesia sarmienti aqueous extract on A549 cells in vitro and S180 cells in vivo.

The effects of Bulnesia sarmienti (BS) aqueous extract on the cell growth of A549 cell lines were investigated. BS has strong cytotoxic activity on the A549 cell lines (IC(50); less than 100 microg/mL) in MTT assay. HPLC confirmed that BS contains catechins as major compound. Cell cycle analysis by flow cytometry indicated that BS arrested the cell cycle in the sub-G(1) phase. BS induced DNA fragmentation, and increased the expression of the p53 protein in immunoblot analysis. These results indicated that the anticancer effect of BS was mediated via the process of apoptosis and growth-inhibition.

A novel beta-glucan produced by Paenibacillus polymyxa JB115 induces nitric oxide production in RAW264.7 macrophages.

The effect of extracellular beta-(1-->3), (1-->6)-glucan, produced by Paenibacillus polymyxa JB115, on nitric oxide (NO) production in RAW264.7 macrophages was investigated. beta-glucan induced the production of NO by RAW264.7 macrophages in a concentration- and time-dependent manner. Moreover, beta-glucan stimulation increased the mRNA expression of iNOS, COX-2 and IL-6 in RAW264.7 macrophages in a concentration-dependent manner.

Anticancer activity and apoptotic effects of Bulnesia sarmienti against human lung cancer H460 cells.

Bulnesia sarmienti (BS), a traditional South American herbal medicine native to Gran Chaco, has been used to treat various human ailments. The effects of BS aqueous extract (100, 200, and 400 microg/ml) on H460 cell lines were investigated. High-performance liquid chromatography (HPLC) confirmed that BS contains catechins as major compound. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis, DNA fragmentation, apoptosis, and immunoblot analysis on cells were carried out. BS has strong cytotoxic activity on the H460 cell lines (IC50; less than 100 microg/ml) in MTT assay. Flow cytometry indicated that BS arrested the cell cycle in the sub-G1 phase. When BS was treated on H460 cells, DNA fragmentation was increased, and early apoptotic cells were shown to be positive by annexin V staining. Also, the expressions of the p53 and Bax were increased and Bcl-2 protein was downregulated with BS treatment. These results indicated that the BS has anticancer activity on H460 cells and BS may be useful in future therapeutic applications for developing anticancer agents.

Physiological activities of a beta-glucan produced by Panebacillus polymyxa.

In vitro bioactivities of a beta-glucan produced by Panebacillus polymyxa JB115 were investigated. Nitric oxide production by RAW 264.7 macrophage cells pre-treated with beta-glucan JB115 (from 0.1 to 1 mg ml(-1)) was significantly increased, compared to that in untreated cells (P < 0.001). The beta-glucan JB115 increased superoxide radical-scavenging activity by 66% at 1 mg ml(-1). It also suppressed hyaluronidase (32%) and collagenase (33%) activities and, additionally, displayed antitumor activity, blocking the growth of Sarcoma 180 cells in a concentration-dependent manner. The immune-stimulatory, antioxidant, collagenase inhibitory and hyaluronidase inhibitory effects of the beta-glucan support its potential role in the prevention of bacterial disease against fish and in the protection of skin against aging.