Efficacy of Crataegus Extract Mixture on Body Fat and Lipid Profiles in Overweight Adults: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

A Crataegus Extract Mixture (CEM) is a combination of extracts from Crataegus pinnatifida leaves and Citrus unshiu peels, well-known herbs used for treating obesity and dyslipidemia. We aimed to investigate the efficacy and safety of a CEM on the body fat and lipid profiles in overweight adults. A 12-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted on 105 subjects aged 20-60 years with body mass indexes between 25 and 30 kg/m2. Eligible subjects were randomly assigned in a 1:1:1 ratio to receive either a high dose of the CEM (400 mg tid), a low dose of the CEM (280 mg tid), or a placebo. Body fat was evaluated using dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and anthropometric measurements. The blood lipid and adipokine profiles were measured before and after the administration. After 12 weeks, the reductions in the fat percentages measured by DXA and BIA were significantly greater in the CEM groups than in the placebo group. The CEM also significantly decreased the body weights, body mass indexes, and blood leptin levels. An additional per-protocol analysis revealed that the high dose of the CEM also lowered the blood levels of triglycerides and very low-density lipoprotein cholesterol. No adverse events occurred after the CEM treatment. Our results suggest that CEMs are safe and effective for reducing the body fat and body weight and regulating the blood lipid and leptin levels in overweight or mildly obese individuals.

Creatine supplementation with exercise reduces α-synuclein oligomerization and necroptosis in Parkinson's disease mouse model.

Parkinson's disease (PD) is an incurable neurological disorder that causes typical motor deficits. In this study, we investigated the effects of creatine supplementation and exercise in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We found that 2% creatine supplementation and/or exercise intervention for 4 weeks elicited neurobehavioral recovery and neuroprotective effects regarding dopaminergic cell loss in MPTP-treated mice; this effect implies functional preservation of dopaminergic cells in the substantia nigra, as reflected by tyrosine hydroxylase expression recovery. Creatine and exercise reduced necroptotic activity in dopaminergic cells by lowering mixed lineage kinase domain-like protein (MLKL) modification to active phenotypes (phosphorylation at Ser345 and oligomerization) and phosphorylated receptor-interacting protein kinase 1 (RIPK1) (Ser166-p) and RIPK3 (Ser232-p) levels. In addition, creatine and exercise reduced the MPTP-induced increase in pathogenic α-synuclein forms, such as Ser129 phosphorylation and oligomerization. Furthermore, creatine and exercise had anti-inflammatory and antioxidative effects in MPTP mice, as evidenced by a decrease in microglia activation, NF-κB-dependent pro-inflammatory molecule expression, and increase in antioxidant enzyme expression. These phenotypic changes were associated with the exercise/creatine-induced AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) and sirtuin 3 (SIRT3)/forkhead box O3 (FoxO3a) signaling pathways. In all experiments, combining creatine with exercise resulted in considerable improvement over either treatment alone. Consequently, these findings suggest that creatine supplementation with exercise has anti-inflammatory, antioxidative, and anti-α-synucleinopathy effects, thereby reducing necroptotic cell death in a PD mouse model.

Combined IgE neutralization and Bifidobacterium longum supplementation reduces the allergic response in models of food allergy.

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.

Blood Salvage and Autotransfusion With Single Leukoreduction Does Not Increase the Risk of Tumor Recurrence After Liver Transplantation for Advanced Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC). BACKGROUND: Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC. METHODS: Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74 of 129 without autotransfusion were matched with 74 of 220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence. RESULTS: Recipients in autotransfusion group received 811 (497-1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/ 38.3%/39.7% for nonautotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the 2 groups in overall recurrence [hazard ratio (HR) = 0.72 (0.43-1.21)], intrahepatic recurrence [HR = 0.70 (0.35-1.40)], and extrahepatic recurrence [HR = 0.82 (0.46-1.47)]. Also, there were no significant differences in overall death [HR = 0.57 (0.29-1.12)], HCC-related death [HR = 0.59 (0.29-1.20)], and HCC-unrelated death [HR = 0.48 (0.09-2.65)]. CONCLUSIONS: When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.

Hypothalamic administration of sargahydroquinoic acid elevates peripheral thermogenic signaling and ameliorates high fat diet-induced obesity through the sympathetic nervous system.

Sargassum serratifolium (C. Agardh) C.Agardh, a marine brown alga, has been consumed as a food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome when orally supplemented. Sargahydroquinoic acid (SHQA) is a major component of MES. However, it is unclear whether SHQA regulates energy homeostasis through the central nervous system. To examine this, SHQA was administrated through the third ventricle in the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Chronic administration of SHQA into the brain reduced body weight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicated that SHQA elevated thermogenic signaling pathways, as evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. Peripheral denervation experiments using 6-OHDA indicated that the SHQA-induced anti-obesity effect is mediated by the activation of the sympathetic nervous system, possibly by regulating genes associated with sympathetic outflow and GABA signaling pathways. In conclusion, hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.

The Potential Role of Korean Mistletoe Extract as an Anti-Inflammatory Supplementation.

Korean mistletoe has anti-inflammatory and antioxidant functions and may be a useful training supplement. We investigated the effect of Korean mistletoe extract (KME) on inflammatory markers after high-intensity exercise by 20 university male rowers (KME group vs. CON group) consuming 110 mL KME/dose (2 times a day over 8 weeks). Blood samples were collected for measurement of serum cytokine levels at baseline, immediately after exercise, and following 30 minutes of recovery. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were used as markers for inflammation. After supplementation, IL-6 and TNF-α levels were significantly lowered in the KME group than in the CON group at baseline, immediately after exercise, and following 30 minutes of recovery. KME can reduce high-strength exercise-induced increases in the levels of serum inflammatory cytokines in active individuals and improve anti-inflammatory functions.

Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy.

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.

Ginsenoside F2 induces cellular toxicity to glioblastoma through the impairment of mitochondrial function.

BACKGROUND: Glioblastoma (GBM) is the most aggressive tumor residing within the central nervous system, with extremely poor prognosis. Although the cytotoxic effects of ginsenoside F2 (GF2) on GBM were previously suggested, the precise anti-GBM mechanism of GF2 remains unclear. The aim of this study was to explore the anti-cancer molecular mechanism of GF2 toward human GBM. METHODS: GF2-driven cellular toxicity was confirmed in two different GBM cells, U373 and Hs683. To test mitochondrial impairment driven by GF2, we examined the mitochondrial membrane potential, OCR, and ATP production. An intracellular redox imbalance was identified by measuring the relative ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), glutaredoxin (GLRX) mRNA expression, intracellular NAD+ level, and AMPK phosphorylation status. RESULTS: GF2 increased the percentage of cleaved caspase 3-positive cells and γH2AX signal intensities, confirming that GF2 shows the cytotoxicity against GBM. GO enrichment analysis suggested that the mitochondrial function could be negatively influenced by GF2. GF2 reduced the mitochondrial membrane potential, basal mitochondrial respiratory rate, and ATP production capacity. Our results showed that GF2 downregulated the relative GSH/GSSG, intracellular NAD+ level, and GLRX expression, suggesting that GF2 may alter the intracellular redox balance that led to mitochondrial impairment. CONCLUSION: GF2 reduces mitochondrial membrane potential, inhibits cellular oxygen consumption, activates AMPK signaling, and induces cell death. Our study examined the potential vulnerability of mitochondrial activity in GBM, and this may hold therapeutic promise.

Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary or secondary liver cancer. However, conventional TACE formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. Methods: To overcome these limitations, a doxorubicin-loaded albumin nanoparticle-conjugated microbubble complex in an iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) has been developed as a new ultrasound-triggered TACE formulation. Results: (1) Microbubbles enhanced therapeutic efficacy by effectively delivering doxorubicin- loaded nanoparticles into liver tumors via sonoporation under ultrasound irradiation (US+). (2) Microbubbles constituting the complex retained their function as an ultrasound contrast agent in Lipiodol. In a rabbit VX2 liver cancer model, the in vivo study of DOX-NPs-MB complex in Lipiodol (US+) decreased the viability of tumor more than the conventional TACE formulation, and in particular, effectively killed cancer cells in the tumor periphery. Conclusion: Incorporation of doxorubicin-loaded microbubble in the TACE formulation facilitated drug delivery to the tumor with real-time monitoring and enhanced the therapeutic efficacy of TACE. Thus, the enhanced TACE formulation may represent a new treatment strategy against liver cancer.

Association Between Erythrocyte Levels of n-3 Polyunsaturated Fatty Acids and Risk of Frailty in Community-Dwelling Older Adults: The Korean Frailty and Aging Cohort Study.

BACKGROUND: Inflammation is a major risk factor for frailty, but n-3 polyunsaturated fatty acids (PUFA) has been suggested as an anti-inflammatory agent. The present study aimed to investigate the hypothesis that the higher erythrocyte levels of long-chain n-3 PUFA were associated with lower odds of frailty and frailty criterion. METHODS: Cross-sectional analysis from the Korean Frailty and Aging Cohort Study, a total of 1,435 people aged 70-84 years were included. Sex- and age-stratified community residents, drawn in urban and rural regions nationwide, were eligible for participation in the study. All participants were categorized as frail and nonfrail according to the Cardiovascular Health Study index. RESULTS: The likelihood of frailty was inversely associated with the erythrocyte levels of eicosapentaenoic acid (EPA; odds ratio [OR] per unit 0.33; 95% confidence interval [CI] 0.14-0.77; p for trend = .002) and docosahexaenoic acid (DHA; OR per unit 0.42; 95% CI 0.20-0.87; p for trend = .018). Among each frailty criterion, the likelihood of slow walking speed was associated with erythrocyte levels of EPA and DHA, and the likelihood of exhaustion was inversely associated with the erythrocyte levels of DHA. CONCLUSIONS: The present study showed that the frailty and frailty criterion were significantly associated with lower erythrocyte levels of long-chain n-3 PUFA, suggesting that lower n-3 PUFA could be a marker for the risk of frailty.

Quadrella incana (Capparaceae) Leaf Extract Enhances Proliferation and Maintenance of Neural Stem/Progenitor Cells through Upregulating Glycolytic Flux and Redox Potential.

Neural stem/progenitor cells (NSPCs) are self-renewing, multipotent cells located in the embryonic and adult central nervous system (CNS). Extensive preclinical and clinical studies have shed light on the potential of stem cell replacement therapy for various neurodegenerative diseases. The key prerequisite for the success of these clinical applications is the procurement of a sufficient number of high-quality NSPCs. In this study, we explored the biological activity of Quadrella incana leaf in NSPC homeostasis. We showed that the leaf extract of Quadrella incana upregulated NSPC marker and proliferative potential. On the other hand, Quadrella incana leaf suppressed spontaneous unintended NSPC differentiation. Mechanistically, Quadrella incana leaf contributed to the maintenance of NSPCs by upregulating glycolytic flux and redox potential.

Hemistepsin A alleviates liver fibrosis by inducing apoptosis of activated hepatic stellate cells via inhibition of nuclear factor-κB and Akt.

Hemistepsin A (HsA), isolated from Hemistepta lyrata (Bunge) Bunge, has the ability to ameliorate hepatitis in mice. However, the effects of H. lyrata and HsA on other types of liver disease have not been explored. In this report, we investigated the effects of H. lyrata and HsA on liver fibrosis and the underlying molecular mechanisms in activated hepatic stellate cells (HSCs). Based on cell viability-guided isolation, we found HsA was the major natural product responsible for H. lyrata-mediated cytotoxicity in LX-2 cells. HsA significantly decreased the viability of LX-2 cells and primary activated HSCs, increased the binding of Annexin V, and altered the expression of apoptosis-related proteins, suggesting that HsA induces apoptosis in activated HSCs. HsA reduced the phosphorylation of IKKε and the transactivation of nuclear factor-κB (NF-κB). Moreover, HsA decreased the phosphorylation of Akt and its downstream signaling molecules. Transfection experiments suggested that inhibition of NF-κB or Akt is essential for HsA-induced apoptosis of HSCs. In a CCl4-induced liver fibrosis model, HsA administration significantly decreased ALT and AST activities. Furthermore, HsA attenuated CCl4-mediated collagen deposits and profibrogenic genes expression in hepatic tissue. Thus, HsA may serve as a natural product for managing liver fibrosis through inhibition of NF-κB/Akt-dependent signaling.

Nutritional Therapy for Asian Patients at Risk for Atherosclerotic Cardiovascular Disease.

The burden of atherosclerotic cardiovascular disease (ASCVD) remains high worldwide, and its prevalence has increased in Asian countries over the last two decades. The increase in ASCVD may arise from complex interactions between genetic and lifestyle/environmental factors. Abnormal blood cholesterol levels, elevated blood glucose, obesity, elevated blood pressure, smoking, and family history are common risk factors of ASCVD. There is an increased burden of ASCVD in Asian countries, maybe due to rapid economic development and lifestyle changes in these countries. Nutrition is one of the major modifiable risk factors for ASCVD. Despite this, there are insufficient nutritional therapies for prevention and management of ASCVD in Asian patients. There is also a lack of relevant research in Asian populations. In this review, we describe the current nutritional guidelines and the findings from previous landmark studies regarding management and/or prevention of ASCVD. We also summarize the recommendations regarding evidence-based nutrition therapy/management strategies that may be effective in Asian subjects to prevent onset and/or to treat ASCVD.

Effects of aquatic and land-based exercises on amyloid beta, heat shock protein 27, and pulse wave velocity in elderly women.

BACKGROUND: Alzheimer's disease is a neurodegenerative brain disease resulting from the deterioration of neuronal cells and vascular dementia, the latter of which results from cerebrovascular disorders. Exercise is effective in preventing and treating degenerative brain diseases as it activates blood flow to the brain, increases nerve production in the hippocampus, and promotes the expression of synaptic plasticity-related proteins. Therefore, this study investigated the effects of 16-week aquatic and land-based exercise programs on amyloid beta (Aß), heat shock protein (HSP) 27 levels, and pulse wave velocity (PWV). MATERIALS AND METHODS: Forty elderly women, aged 60-70 years, voluntarily participated in the study. They were divided into control (n = 12), aquatic exercise (n = 14), and land-based exercise groups (n = 14). The variables of amyloid beta, heat shock protein 27, and pulse wave velocity were measured in all the participants before and after the 16-week study. RESULTS: Significantly higher levels of serum HSP27 (p < 0.05) and significantly lower levels of vascular elasticity (p < 0.05) were found in the aquatic exercise group after 16 weeks of exercise compared with the control group. Aß did not significantly differ between groups. Thirty minutes after the first exercise, Aß in the aquatic exercise group (p < 0.01) and HSP27 in the land-based exercise group (p < 0.05) were significantly higher than the corresponding levels in the resting condition before exercise. 30 min after the last exercise, Aß (p < 0.01) and HSP27 (p < 0.05) were significantly higher. CONCLUSIONS: Aquatic and land-based exercises increased serum Aß and HSP27 and decreased pulse wave velocity. Thus, they may play a positive role in the prevention of degenerative brain diseases and improvement of brain function in elderly people.

Cellular toxicity driven by high-dose vitamin C on normal and cancer stem cells.

As a powerful antioxidant, vitamin C protects cells from oxidative damage by inhibiting production of free radicals. However, high levels of vitamin C shows cytotoxicity especially on cancerous cells through generating excessive ROS and blocking the energy homeostasis. Although the double-sided character of vitamin C has been extensively studied in many cell types, there is little research on the consequence of vitamin C treatment in stem cells. Here, we identified that high-dose vitamin C shows cellular toxicity on proliferating NSPCs. We also demonstrated that undifferentiated NSPCs are more sensitive to vitamin C-driven DNA damage than differentiated cells, due to higher expression of Glut genes. Finally, we showed that high-dose vitamin C selectively induces DNA damage on cancer stem cells rather than differentiated tumor cells, raising a possibility that vitamin C may be used to target cancer stem cells.

Effects of aquarobic exercise and burdock intake on serum blood lipids and vascular elasticity in Korean elderly women.

BACKGROUND: The elderly's health issues are often complex and tend to lead to chronic diseases; such issues can be due to a fitness decline resulting from a lack of physical activities. The burdock root is a blood purifier, lymphatic system strengthener, and natural diuretic. The purpose of this study was to analyze the effects of aquarobic exercise and burdock intake on serum blood lipids and vascular elasticity in elderly women by implementing a 12-week program with these interventions. METHODS: Forty elderly female volunteer subjects aged 70 to 80years comprised the control group (n=8), aquarobic exercise group (n=11), aquarobic exercise and burdock intake combination group (n=11), and burdock intake group (n=10). The variables of serum blood lipids, and vascular elasticity were measured in all participants before and after the 12-week study. RESULTS: Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels significantly decreased in the aquarobic exercise group and aquarobic exercise and burdock intake combination group (p<0.05, p<0.01, p<0.001). No statistically significant changes in pulse wave velocity were also found within or between the groups before and after participation in the 12-week program. CONCLUSIONS: Our findings indicate that aquarobic exercise and burdock intake improved the serum blood lipid levels and vascular elasticity of Korean elderly women. Additionally, burdock extract intake may be useful in vascular health by playing a secondary role in disease prevention and health promotion.

Effects of Vitamin C Supplementation on Plasma and Urinary Vitamin C Concentration in Korean Women.

Although vitamin C supplements were consumed for health maintenance and fatigue recovery, the effects of high doses of vitamin C supplement remains controversial. Our study performed the effects of 100 mg and 2,000 mg vitamin C supplements on plasma and urinary vitamin C concentration in Korean women. Twenty-four women completed the 4 weeks intervention. Anthropometric data, plasma and urinary vitamin C concentrations, superoxide dismutase activity, thiobarbituric acid reactive substance (TBARS) level, and fatigue severity scale (FSS) were collected, and the statistical analyses compared between- and within-group findings at pre- and post-intervention. Concentrations of vitamin C in plasma and urinary excretion were significantly increased with 100 mg and 2,000 mg of vitamin C supplementation (p < 0.050). TBARS level was decreased significantly with 2,000 mg of vitamin C supplementation (p < 0.050). In addition, FSS was declined significantly in 100 mg of vitamin C supplementation group (p < 0.050). Our result showed that vitamin C supplementation of either 100 mg or 2,000 mg led to an increase in vitamin C concentrations in plasma and vitamin urinary excretion but not statistically significant among groups. TBARS level was decreased in 2,000 mg and FSS was decreased in 100 mg of vitamin C supplementation in Korean women. We suppose that additional clinical trial is needed to examine the effects of vitamin C supplements for a wide range of doses on plasma and urinary vitamin C concentrations in Korean.

Anti-diabetic effect of black ginseng extract by augmentation of AMPK protein activity and upregulation of GLUT2 and GLUT4 expression in db/db mice.

BACKGROUND: Black ginseng (Panax ginseng C. A. Meyer), three to nine times-steamed and dried ginseng, has biological and pharmacological activities. In this study, the anti-diabetic effects of the black ginseng ethanol extract (GBG05-FF) in typical type 2 diabetic model db/db mice were investigated. METHODS: The effect of GBG05-FF in Type 2 diabetic mice was investigated by their blood analysis, biological mechanism analysis, and histological analysis. RESULTS: The mice group treated with GBG05-FF showed decreased fasting blood glucose and glucose tolerance compared to that of the nontreated GBG05-FF group. In the blood analysis, GBG05-FF decreased main plasma parameter such as HbA1c, triglyceride, and total-cholesterol levels related to diabetes and improved the expression of genes and protein related to glucose homeostasis and glucose uptake in the liver and muscle. The histological analysis result shows that GBG05-FF decreased lipid accumulation in the liver and damage in the muscle. Moreover, GBG05-FF increased the phosphorylation of the AMPK in the liver and upregulated the expression of GLUT2 in liver and GLUT4 in muscle. Therefore, the mechanisms of GBG05-FF may be related to suppressing gluconeogenesis by activating AMPK in the liver and affecting glucose uptake in surrounding tissues via the upregulation of GLUT2 and GLUT4 expression. CONCLUSION: These findings provided a new insight into the anti-diabetic clinical applications of GBG05-FF and it might play an important role in the development of promising functional foods and drugs from the viewpoint of the chemical composition and biological activities.

Effect of high hydrostatic pressure treatment on isoquercetin production from rutin by commercial α-L-rhamnosidase.

OBJECTIVES: To optimize conversion of rutin to isoquercetin by commercial α-L-rhamnosidase using high hydrostatic pressure (HHP). RESULTS: The de-rhamnosylation activity of α-L-rhamnosidase for isoquercetin production was maximal at pH 6.0 and 50 °C using HHP (150 MPa). The enzyme showed high specificity for rutin. The specific activity for rutin at HHP was 1.5-fold higher than that at atmospheric pressure. The enzyme completely hydrolysed 20 mM rutin in tartary buckwheat extract after 2 h at HHP, with a productivity of 10 mM h(-1). The productivity and conversion were 2.2- and 1.5-fold higher at HHP than at atmospheric pressure, respectively. CONCLUSIONS: This is the first report concerning the enzymatic hydrolysis of isoquercetin in tartary buckwheat at HHP.

Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer, Araliaceae) has been used as a traditional medicine for thousands of years for the treatment of a wide variety of diseases, including diabetes. Processed ginseng named Black ginseng exhibits more potent biological activities than white and red ginseng. The aim of this study was to investigate the effects of black ginseng extract (GBG05-FF) on hyperglycemia and glucose tolerance in streptozotocin (STZ)-induced diabetic mice. MATERIALS AND METHODS: Black ginseng was produced by a repeated steaming and drying process, subsequent extraction with 70% ethanol, filtration, and lyophilization. The effect of GBG05-FF on glucose uptake and related protein expression and phosphorylation were determined in C2C12 cells. Furthermore, we evaluated the anti-diabetic effects of GBG05-FF in STZ-induced diabetic mice. RESULTS: GBG05-FF significantly (p<0.05) increased glucose uptake in C2C12 myotubes via AMPK, Sirt1 and PI3-K pathway. In addition, GBG05-FF improved the fasting blood glucose levels and glucose tolerance in STZ-induced diabetic mice. GBG05-FF decreased blood parameters such as glycated hemoglobin, triglyceride and total cholesterol. Quantitative RT-PCR assay revealed that in the STZ-induced diabetic mice treated with GBG05-FF, the expression of hepatic genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase)), glycogenolysis (liver glycogen phosphorylase (LGP)) and glycogenesis (glycogen synthase (GS)) was suppressed, while the expression of the genes involved in glucose uptake (glucose transporter (GLUT) 1, GLUT4) and ß-oxidation (acyl-CoA oxidase (ACO), carnitine palmitoyl transferase 1a (CPT1a), mitochondrial medium chain acyl-CoA dehydrogenase (MCAD)) in muscle were increased. GBG05-FF delayed diabetes-associated muscle atrophy by activating mTOR. The major bioactive compounds including ginsenoside Rg1, Rg3(S), Rg3(R), Rg5, Rk1 and Rh4 were evaluated for glucose uptake effect in C2C12 myotubes; the data indicated that Rh4 significantly (p<0.05) increased glucose uptake. CONCLUSION: Collectively, the results suggested that GBG05-FF is a potentially useful agent for treatment of diabetes by increasing glucose uptake.