Protective Effect of Whole Wheat on Muscle Atrophy in C2C12 Cells via Akt/FoxO1 Signaling Pathways.

Skeletal muscles are important for body movement, postural maintenance, and energy metabolism. Muscle atrophy is caused by various factors, including lack of exercise, age, genetics, and malnutrition, leading to the loss of muscle mass. The Akt/FoxO signaling pathway plays a key role in the regulation of muscle protein synthesis and degradation. Whole wheat contains functional ingredients that may indirectly contribute to muscle health and function and can help prevent or slow the progression of muscle atrophy. In this study, the protective effects of three wheat cultivars (Seodun, Ol, and Shinmichal 1) against hydrogen peroxide-induced muscle atrophy in C2C12 cells were investigated. We found that whole-wheat treatment reduced reactive oxygen species production, prevented glutathione depletion, and increased myotube diameter, thereby reducing muscle atrophy by activating myoblast differentiation. Generally, "Shinmichal 1" exhibited the highest activation of the Akt/FoxO signaling pathway. In contrast, "Seodun" showed similar or slightly higher activities than those of the H2O2-treated only group. In conclusion, whole wheat exerts a protective effect against muscle atrophy by activating the Akt/FoxO signaling pathway. This study indicates that whole wheat may help prevent muscle atrophy.

Synergistic Effect of Madecassoside and Rosmarinic Acid Against Ultraviolet B-Induced Photoaging in Human Skin Fibroblasts.

Madecassoside (MD) and rosmarinic acid (RA) are well-known compounds with wound healing and antiaging effects. We demonstrated the synergistic protective activity of the MD-RA combination in Hs68 cells against ultraviolet B (UVB)-induced photoaging. The cell viabilities of MD, RA, and MD-RA combinations at various ratios (9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, and 1:9, v/v) were measured to compare their protective effects against UVB radiation. The synergistic interaction between MD and RA was confirmed using a combination index. The strongest effect of the MD-RA combination was observed at a ratio of 3:7. The combination of MD-RA 3:7 exerted a synergistic effect against UVB-induced changes in cell viability, as well as superoxide dismutase activity, reactive oxygen species, glutathione, catalase activity, and malondialdehyde levels. Moreover, the inhibitory effect of the MD-RA combination (3:7) on matrix metalloproteinases and total collagen production was higher than that of MD or RA alone. These results demonstrated that the MD-RA combination (3:7) generated a strong synergistic effect against UVB-induced photoaging in Hs68 cells. Overall, our results provide scientific evidence to support the development of a new combination therapy for skin protection against UVB-induced photoaging through the synergistic interaction between MD and RA. These natural compounds are promising options for antiaging and skin protection in the cosmetic and pharmaceutical industries.

Enhancement of bioactive compounds and biological activities of Centella asiatica through ultrasound treatment.

Centella asiatica possess various health-promoting activities owing to its bioactive compounds such as triterpenes, flavonoids, and vitamins. Ultrasound treatment during the post-harvest process is a good strategy for eliciting secondary metabolite in plants. The present study investigated the effect of ultrasound treatment for different time durations on the bioactive compounds and biological activities of C. asiatica leaves. The leaves were treated with ultrasound for 5, 10, and 20 min. Ultrasound elicitation (especially for 10 min) markedly elevated the accumulation of stress markers, leading to enhanced phenolic-triggering enzyme activities. The accumulation of secondary metabolites and antioxidant activities were also significantly improved compared with that in untreated leaves. In addition, ultrasound-treated C. asiatica leaves protected myoblasts against H2O2-induced oxidative stress by regulating reactive oxygen species production, glutathione depletion, and lipid peroxidation. These findings indicate that elicitation using ultrasound can be a simple method for increasing functional compound production and enhancing biological activities in C. asiatica leaves.

Antioxidant and Skin Whitening Activities of Sub- and Super-Critical Water Treated Rutin.

We focused on the functional components, antioxidant activity, skin-whitening, and anti-wrinkle properties of subcritical and supercritical water (SCW)-treated rutin. Rutin treatments were performed at the following temperature and pressure conditions: 200 °C/15 bar, 300 °C/100 bar, and 400 °C/250 bar. ABTS and DPPH radical scavenging activities and reducing power presented their highest values (1193.72 mg AAE/g, 728.73 mg AAE/g, and 0.65, respectively) at 300 °C/100 bar. The tyrosinase inhibitory activity of SCW-treated rutin was 21.72-60.05% at 1 mg/mL. The ethyl acetate fraction showed 14.91% melanin inhibitory activity at a concentration of 10 µg/mL compared to the α-MSH treatment group. The protein expression inhibition rates of MITF, tyrosinase, TRP-1, and TRP-2 in the ethyl acetate fractions were 14.05%, 72%, 93.05%, and 53.44%, respectively, at a concentration of 10 µg/mL, compared to the control. These results indicate that SCW treatment could be used to develop cosmetic materials and functional food with physiological activity, and that SCW-treated rutin can be used as a skin-whitening cosmetic material.

The Effect of Drug Pricing on Outpatient Payments and Treatment for Three Soil-Transmitted Helminth Infections in the United States, 2010-2017.

The price of certain antiparasitic drugs (e.g., albendazole and mebendazole) has dramatically increased since 2010. The effect of these rising prices on treatment costs and use of standard of care (SOC) drugs is unknown. To measure the impact of drug prices on overall outpatient cost and quality of care, we identified outpatient visits associated with ascariasis, hookworm, and trichuriasis infections from the 2010 to 2017 MarketScan Commercial Claims and Encounters and Multi-state Medicaid databases using Truven Health MarketScan Treatment Pathways. Evaluation was limited to members with continuous enrollment in non-capitated plans 30 days prior, and 90 days following, the first diagnosis. The utilization of SOC prescriptions was considered a marker for quality of care. The impact of drug price on the outpatient expenses was measured by comparing the changes in drug and nondrug outpatient payments per patient through Welch's two sample t-tests. The total outpatient payments per patient (drug and nondrug), for the three parasitic infections, increased between 2010 and 2017. The increase was driven primarily by prescription drug payments, which increased 20.6-137.0 times, as compared with nondrug outpatient payments, which increased 0.3-2.2 times. As prices of mebendazole and albendazole increased, a shift to alternative SOC and non-SOC drug utilization was observed. Using parasitic infection treatment as a model, increases in prescription drug prices can act as the primary driver of increasing outpatient care costs. Simultaneously, there was a shift to alternative SOC, but also to non-SOC drug treatment, suggesting a decrease in quality of care.

Protective effect of gamma-aminobutyric acid against oxidative stress by inducing phase II enzymes in C2C12 myoblast cells.

In this study, the cytoprotective effect of gamma-aminobutyric acid (GABA) via inducing phase II enzymes in C2C12 myoblasts was evaluated. The highest concentration of GABA (100 µM) significantly increased the cell viability by approximately 90% in hydrogen peroxide-induced C2C12 cells. The treatment with GABA (100 µM) effectively decreased the glutathione (GSH) depletion and the activities of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). And, reactive oxygen species (ROS) levels were effectively reduced by about 50% in GABA-treated cells. In addition, the protein expression of phase II enzymes, such as NADPH:quinone oxidoreductase 1 and heme oxygenase-1 was significantly increased by GABA treatment. Moreover, GABA treatment increased the nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the nucleus of C2C12 myoblasts. Altogether, the results in this study indicate that GABA possesses the cytoprotective effects against oxidative insults by regulating the GSH levels, CAT and SOD activities, ROS scavenging activities, and expression of phase II enzymes through the activation of Nrf2 in C2C12 cells. Hence, this study suggests that the GABA supplementation could be effective in alleviating oxidative stress-induced muscle damage. PRACTICAL APPLICATIONS: GABA exists in the germ and bran layers of rice and is well-known as the inhibitory neurotransmitter in the central nervous system. GABA also has various health beneficial effects, such as preventing chronic alcohol-related diseases and lowering blood pressure. The present study shows the cytoprotective effect of GABA against oxidative stress in C2C12 myoblasts, and suggests that GABA has great potential as a functional food ingredient for attenuating oxidative stress-induced muscle damage.

Effect of Deglycosylated Rutin by Acid Hydrolysis on Obesity and Hyperlipidemia in High-Fat Diet-Induced Obese Mice.

The present study evaluated the effects of acid-treated rutin on hyperlipidemia and obesity in high-fat diet (HFD)-induced obese mice. The mice consumed a HFD with or without acid-treated rutin for 7 weeks. Body weight gain considerably decreased, by approximately 33%, in the acid-treated rutin (AR) and quercetin (Q) groups compared to that in the HFD group. The adipocytes' size in epididymal fat in AR and Q groups was significantly reduced compared to that in the HFD group (p < 0.05). Treatment with AR decreased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol compared to the HFD group. In particular, administration of AR significantly decreased serum triglyceride (36.82 mg/dL) by 46% compared to HFD (69.30 mg/dL). The AR group also showed significantly decreased atherogenic indices and cardiac risk factors. These results suggest that deglycosylated rutin generated by acid treatment enhances the anti-obesity and hypolipidemic effects in obese mice, and provides valuable information for improving the functional properties of glycosidic flavonoids.

Effect of calcium chloride and sucrose on the composition of bioactive compounds and antioxidant activities in buckwheat sprouts.

In this study, we evaluated the effect of sucrose and CaCl2 on the growth profile, nutritional quality, and antioxidant capacity of sprouted buckwheat. Buckwheat seeds were germinated at 25 °C for 8 days and sprayed with four different solutions: distilled water, 3% sucrose, 7.5 mM CaCl2, and 3% sucrose plus 7.5 mM CaCl2. Our results showed that CaCl2 effectively improved sucrose-elicitation induced growth reduction in buckwheat sprouts. Elicitation with both sucrose and CaCl2 in buckwheat sprouts markedly enhanced the accumulation of bioactive compounds, such as polyphenols, flavonoids, γ-aminobutyric acid, vitamin C, and E, without negatively affecting sprout growth. Elicitation with both sucrose and CaCl2 not only significantly enhanced the antioxidant activities but also exerted cytoprotective effects against oxidative damage in HepG2 cells and fibroblasts. These findings suggested that simultaneous elicitation with 3% sucrose and 7.5 mM CaCl2 can potentially improve the nutritional value and potential health benefits of buckwheat sprouts.

Jujube (Ziziphus jujuba Mill.) Protects Hepatocytes against Alcohol-Induced Damage through Nrf2 Activation.

This study aimed at evaluating the cytoprotective activity of jujube water extract (JWE) against alcohol-induced oxidative stress via the activation of the Nrf2 pathway in HepG2 cells. JWE had various phenolic compounds, and the vanillic acid content was the highest in the extract. To determine the cytoprotective effect of JWE against alcohol-induced damage, hepatocytes were treated with JWE and 3% ethanol. JWE (100 µg/mL) markedly increased cell viability by approximately 100% in a dose-dependent manner. Moreover, JWE attenuated the production of malondialdehyde, reactive oxygen species, aspartate, and alanine aminotransferase and the depletion of glutathione. Moreover, JWE enhanced the expression of antioxidant defense enzymes including heme oxygenase-1, NADPH quinone oxidoreductase 1, and γ-glutamate-cysteine ligase catalytic against alcohol-induced oxidative damage in hepatocytes via the activation of Nrf2. Taken together, JWE possesses the protective effect against alcohol-induced oxidative injury in hepatocytes through the upregulation of the Nrf2 signaling pathway. Therefore, jujube fruit might have the potential to improve alcohol-related liver problems.

Preparation of High Purity Δ5-Olefinic Acids from Pine Nut Oil via Repeated Lipase-Catalyzed Esterification.

Δ5-Olefinic acids have been characterized in gymnosperm plants and have been reported to have several biological health benefits. Δ5-Olefinic acids from pine nut oil were effectively concentrated by repeated lipase-catalyzed esterification. The pine nut oil contained three major Δ5-olefinic acids, namely taxoleic acid (C18:2 Δ5,9), pinolenic acid (C18:3 Δ5,9,12), and sciadonic acid (C20:3 Δ5,11,14). The fatty acids present in pine nut oil were selectively esterified with ethanol using Lipozyme RM IM from Rhizomucor miehei as a biocatalyst. The Δ5-olefinic acids were concentrated in the unesterified fatty acid fraction. The optimum molar ratio of the substrates (fatty acid:ethanol), temperature, the enzyme loading, and the reaction time were 1:7, 25°C, 5% of total substrate weight, and 6 h, respectively. There was no significant effect in the concentration of Δ5-olefinic acids when water was added in the reaction mixture. The same protocol and optimum conditions were employed for two times repeated lipase-catalyzed esterifications. In first lipase-catalyzed esterification, the Δ5-olefinic acids content in the pine nut oil increased from 17 mol% to 51 mol% with a yield of 40 mol%. In a second lipase-catalyzed esterification, with the Δ5-olefinic acids-concentrated fatty acids obtained from the first reaction as the substrate, the Δ5-olefinic acids content increased to 86 mol% with a yield of 15 mol%. Finally, a maximum Δ5-olefinic acids content of ca. 96 mol% with a yield of 6 mol% was obtained via a third lipase-catalyzed esterification.

Influence of organic acids and heat treatment on ginsenoside conversion.

BACKGROUND: Heat treatments are applied to ginseng products in order to improve physiological activities through the conversion of ginsenosides, which are key bioactive components. During heat treatment, organic acids can affect ginsenoside conversion. Therefore, the influence of organic acids during heat treatment should be considered. METHODS: Raw ginseng, crude saponin, and ginsenoside Rb1 standard with different organic acids were treated at 130°C, and the chemical components, including ginsenosides and organic acids, were analyzed. RESULTS: The organic acid content in raw ginseng was 5.55%. Organic acids were not detected in crude saponin that was not subjected to heat treatment, whereas organic acids were found in crude saponin subjected to heat treatment. Major ginsenosides (Rb1, Re, and Rg1) in ginseng and crude saponin were converted to minor ginsenosides at 130°C; the ginsenoside Rb1 standard was very stable in the absence of organic acids and was converted into minor ginsenosides in the presence of organic acids at high temperatures. CONCLUSION: The major factor affecting ginsenoside conversion was organic acids in ginseng. Therefore, the organic acid content as well as ginsenoside content and processing conditions should be considered important factors affecting the quality of ginseng products.

Nobiletin Inhibits Hepatic Lipogenesis via Activation of AMP-Activated Protein Kinase.

We aimed to investigate the effects of nobiletin on hepatic lipogenesis in high glucose-induced lipid accumulation in HepG2 cells. Nobiletin, a citrus polymethoxyflavonoid with six methoxy groups, is present abundantly in the peels of citrus fruits. HepG2 cells were incubated in Dulbecco's modified Eagle's medium containing high glucose (25 mM) and subsequently treated with nobiletin at different concentrations (5, 25, and 50 µM). Results showed that nobiletin markedly inhibited high glucose-induced hepatic lipid accumulation in HepG2 cells. In addition, it reduced the protein expression of lipogenic factors, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Nobiletin significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Pretreatment with compound C, an AMPK inhibitor, abolished the inhibitory effects of nobiletin on SREBP-1c and FAS expression. These results suggested that nobiletin might attenuate high glucose-induced lipid accumulation in HepG2 hepatocytes via modulation of AMPK signaling pathway. Therefore, nobiletin might be useful for the prevention and treatment of nonalcoholic fatty liver diseases.

Production of Phytosteryl Ester from Echium Oil in a Recirculating Packed Bed Reactor Using an Immobilized Lipase.

The synthesis of phytosteryl ester via the lipase-catalyzed esterification of phytosterol with fatty acid from echium oil was performed in a recirculating packed bed reactor. A commercial lipase from Candida rugosa was immobilized and then used to optimize the reaction conditions for the synthesis of the phytosteryl ester. The parameters investigated were temperature, molar ratio of phytosterol to fatty acid, retention time, and amount of solvent. The optimum conditions were determined as the temperature of 40℃, the molar ratio of 1:3 (phytosterol to fatty acid), the retention time of 3 min, and the solvent amount of 40 mL. The maximum conversion of phytosteryl ester was ca. 90 mol% under the optimum conditions. The major fatty acid in phytosteryl ester synthesized was α-linolenic acid (ca. 38 mol%).

Nobiletin Attenuates the Inflammatory Response Through Heme Oxygenase-1 Induction in the Crosstalk Between Adipocytes and Macrophages.

Crosstalk between adipocytes and macrophages has been suggested to play a crucial role in metabolic disorders such as obesity, insulin resistance, and type 2 diabetes. The objective of this study was to evaluate the effect of nobiletin on the interaction between adipocytes and macrophages. The results showed that nobiletin significantly and dose-dependently inhibited the secretion of inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor (TNF-α), and monocyte chemoattractant protein (MCP)-1, in a coculture of adipocytes and macrophages. The expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), in differentiated 3T3-L1 cells cocultured in transwell system was blocked by nobiletin. Nobiletin also downregulated the expression of inducible NO synthase in cocultured differentiated RAW264.7 cells. Furthermore, heme oxygenase-1 (HO-1) was significantly induced by nobiletin treatment in both cell types, and small interfering (si) RNA-mediated knockdown of HO-1 significantly recovered the inhibitory effects of nobiletin on the NO production in cocultured cells. These results suggest that nobiletin exerts anti-inflammatory effects on the crosstalk between adipocytes and macrophages by inducing HO-1. Nobiletin may have potential for the prevention of obesity-related metabolic diseases.

Anti-Inflammatory Effects of Stearidonic Acid Mediated by Suppression of NF-κB and MAP-Kinase Pathways in Macrophages.

Stearidonic acid (SDA, 18:4n-3) is an omega-3 polyunsaturated fatty acid present in oils derived from plants of the Boraginaceae family. In this study, we determined the anti-inflammatory effects of SDA isolated from echium oil on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages. SDA significantly downregulated the levels of the inducible nitric oxide synthase (iNOS) protein, thereby suppressing the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. In addition, SDA inhibited the nuclear translocation and promoter activity of nuclear factor κB (NFκB) and the phosphorylation of mitogen-activated protein kinases (MAPK) such as extracellular signal regulated kinase 1/2, c-jun N terminal kinase, and p38 in LPS-stimulated RAW 264.7 cells. Our results showed that SDA exerted anti-inflammatory effects by suppressing iNOS-mediated NO production via inactivation of NFκB and MAPK signaling pathways.

Changes of phenolic-acids and vitamin E profiles on germinated rough rice (Oryza sativa L.) treated by high hydrostatic pressure.

This study was performed to investigate changes in the phenolic acid and vitamin E profiles of germinated rough rice following high hydrostatic pressure treatment (HPT). Rough rice was germinated at 37°C for two days and subjected to 0.1, 10, 30, 50, and 100MPa pressures for 24h. The total phenolic acid content increased from 85.37µg/g at 0.1MPa to 183.52µg/g at 100MPa. The highest gallic acid (4.29µg/g), catechin (9.55µg/g), p-coumaric acid (8.36µg/g), ferulic acid (14.99µg/g), salicylic acid (14.88µg/g), naringin (6.18µg/g), trans-cinnamic acid (45.23µg/g), and kaempferol (40.95µg/g) contents occurred in the sample treated at 100MPa after germination. The maximum vitamin E content of about 2.56 (BG) and 4.34mg/100g (AG) were achieved at 30MPa. These result suggest that a combination of HPT and germination are efficient method for enhancement of functionality in rough rice, and clarify the influence of HPT conditions on the vitamin E and phenolic acid in germination rough rice.

Production of Biodiesel from Acid Oil via a Two-Step Enzymatic Transesterification.

A two-step enzymatic transesterification process in a solvent-free system has been developed as a novel approach to the production of biodiesel using acid oil from rice bran oil soapstock. The acid oil consisted of 53.7 wt% fatty acids, 2.4 wt% monoacylglycerols, 9.1 wt% diacylglycerols, 28.8 wt% triacylglycerols, and 6.0 wt% others. Three immobilized lipases were evaluated as potential biocatalysts, including Novozym 435 from Candida antarctica, Lipozyme RM IM from Rhizomucor miehei, and Lipozyme TL IM from Thermomyces lanuginosus. The effects of molar ratio of acid oil to ethanol, temperature, and enzyme loading were investigated to determine the optimum conditions for the transesterification with the three immobilized lipases. The optimum conditions of the three immobilized lipases were a molar ratio of 1:5 (acid oil to ethanol), the temperature range of 30-40°C, and the enzyme loading range of 5-10%. The two-step transesterification was then conducted under the optimum conditions of each lipase. The stepwise use of Novozym 435 and Lipozyme TL IM or Lipozyme RM IM and Lipozyme TL IM resulted in similar or higher levels of yield to the individual lipases. The maximum yields obtained in both stepwise uses were ca. 92%.

Effect of the Capsicoside G-rich Fraction from Pepper (Capsicum annuum L.) Seeds on High-fat Diet-induced Obesity in Mice.

Obesity is one of the most common metabolic syndromes and is a major threat to human health worldwide. Given the size of this problem, there is growing interest in natural agents that may decrease obesity. In this study, we investigated the anti-obesity effect of a capsicoside G-rich fraction (CRF; 13.35% capsicoside G) isolated from pepper seeds in diet-induced obese mice. C57BL/6J mice were fed either a normal diet or a high-fat diet (HFD), with or without CRF (HFD + CRF; 10 and 100 mg/kg body weight). The body weight and food efficiency ratio of mice fed HFD + CRF were lower in comparison to that of mice fed only an HFD. Epididymal adipose tissue weight and adipocyte hypertrophy were significantly lower in HFD + CRF mice than in HFD mice. The fat deposition in the liver of mice fed HFD + CRF was lower compared to that of mice fed only an HFD. CRF significantly reversed the HFD-induced elevation of the expression of key adipocyte differentiation regulators, including peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, sterol regulatory element binding protein 1c, and their target genes. These results suggest that CRF could be used as dietary therapy for the prevention of obesity and obesity-related metabolic diseases. Copyright © 2016 John Wiley & Sons, Ltd.

Comparative effects of plant oils on the cerebral hemorrhage in stroke-prone spontaneously hypertensive rats.

OBJECTIVES: Since oils and fats can induce metabolic syndrome, leading to cardiovascular and cerebrovascular diseases, the present study was performed to find out whether the plant oils affect the cerebral hemorrhage in stroke-prone spontaneously hypertensive (SHR-SP) rats. METHODS: From 47 days of age, male SHR-SP rats were given drinking water containing 1% NaCl to induce hypertension, and simultaneously fed semi-purified diets containing 10% perilla oil, canola oil, or shortening. The onset time of convulsion following cerebral hemorrhage was recorded, and the areas of hemorrhage and infarction were analyzed in the stroke brains. RESULTS: In comparison with 58-day survival of SHR-SP rats during feeding NaCl alone, perilla oil extended the survival time to 68.5 days, whereas canola oil shortened it to 45.7 days. Feeding perilla oil greatly reduced the total volume of cerebral hemorrhage from 17.27% in the control group to 4.53%, while shortening increased the lesions to 21.23%. In a microscopic analysis, perilla oil also markedly decreased the hemorrhagic and infarction lesions to 1/10 of those in control rats, in contrast to an exacerbating effect of shortening. In blood analyses, perilla oil reduced blood total cholesterol and low-density lipoproteins which were increased in SHR-SP, but canola oil further increased them and markedly lowered platelet counts. DISCUSSION: Perilla oil delayed and attenuated cerebral hemorrhage by improving hyperlipidemia in hypertensive stroke animals, in contrast to the aggravating potential of canola oil and shortening. It is suggested that perilla oil should be the first choice oil for improving metabolic syndrome in hypertensive persons at risk of hemorrhagic stroke.