Quercetin supplementation attenuates cisplatin induced myelosuppression in mice through regulation of hematopoietic growth factors and hematopoietic inhibitory factors.

The present study investigated the effects of quercetin on cisplatin (CDDP)-induced common side effect, myelosuppression, and the possible mechanisms in Balb/c mice. The mice were randomly treated with CDDP alone or in combination with quercetin for 14 days. Quercetin was given by intraperitoneal injection (10 mg/kg, 3 times a week; IQ) or by a diet containing 0.1% or 1% quercetin (LQ and HQ, respectively). We found that quercetin supplementation especially HQ and IQ, significantly restored the decrease in number of bone marrow cells, total white blood cells, red blood cells and platelets, and the body weight in mice exposed to CDDP (P≤.05). Similar trends were observed in the number of neutrophils, lymphocytes and monocytes in the plasma. HQ and IQ also increased the levels of hematopoietic growth factors (HGFs), especially in granulocyte-macrophage-colony stimulating factor and IL-9 (P<.05), but decreased the levels of hematopoietic inhibitory factors (HIFs) and oxidative stress in the plasma and the bone marrow in CDDP-exposed mice. Furthermore, both quercetin and quercetin-3-O-glucuronide (Q3G) significantly increase cell viability and inhibited apoptosis at 48 or 72 h (P≤.05), accompanied by increasing HGF levels and decreasing HIF levels in the cultured medium in 32D cells exposed to CDDP. IL-9 siRNA transfection suppressed the effects of quercetin and Q3G on cell viability (P≤.05) in32D cells. In conclusion, our results indicate that quercetin attenuates CDDP-induced myelosuppression through the mechanisms associated with regulation of HGFs and HIFs.

A Pilot Clinical Study of Liquid Ubiquinol Supplementation on Cardiac Function in Pediatric Dilated Cardiomyopathy.

BACKGROUND: Pediatric dilated cardiomyopathy (PDCM) is a life-threatening type of cardiac muscle dysfunction in children. Ubiquinone is a lipid-soluble nutrient that participates in energy synthesis. Recently, a novel hydrophilic ubiquinol supplement was developed. The purpose of this study was to assess the effect of liquid ubiquinol supplementation (10 mg/kg body weight/day) on cardiac function in children with PDCM. METHODS: Ten children diagnosed with PDCM were recruited to this study and administered with liquid ubiquinol for 24 weeks. The cardiac function was measured by echocardiography. The New York Heart Association (NYHA) functional classification was used to assess symptoms of heart failure. Plasma coenzyme Q10 levels were measured during the study. RESULTS: Ejection fraction (EF) and fractional shortening (FS) were significantly higher than the baseline values until week 16 of supplementation. Subjects who had higher plasma coenzyme Q10 concentration had significantly better EF and FS values. In addition, 30% of the subjects showed improvement in the NYHA classification after 24 weeks of supplementation. CONCLUSION: Liquid ubiquinol supplementation is associated with an increase the level of coenzyme Q10 to complementary improve cardiac function (particularly EF and FS) and ameliorate the symptoms of heart failure in children with PDCM.

Does coffee drinking have beneficial effects on bone health of Taiwanese adults? A longitudinal study.

BACKGROUND: Results from studies investigating the association between coffee consumption and osteoporosis or bone mineral density (BMD) have been inconsistent. This longitudinal study was performed to assess the effect of coffee drinking on bone health of Taiwanese adults. METHODS: Data were retrieved from the Li-Shin (Landseed) Hospital in Taoyuan City. In 2006, 6152 participants completed a questionnaire on coffee drinking and other lifestyle factors. In 2014, 5077 of them were followed up. Nonetheless, a total of 2395 participants with incomplete data were excluded. The final analyses included 2682 participants comprising 1195 men and 1487 women (706 premenopausal and 781 postmenopausal). T-scores were derived from the osteo-sono assessment index (OSI) which is a surrogate of BMD. Coffee drinking was categorized as "no, medium, and high" based on the number of cups that were consumed per week in both 2006 and 2014. RESULTS: In general, medium and high coffee drinking were associated with higher T-scores. However, significant results were observed only among high drinkers (ß = 0.158; P = 0.0038). Nonetheless, the test for linear trend was significant (P = 0.0046). After stratification by sex, medium and high coffee drinking were associated with higher T-scores. However, significant results were prominent only among high male drinkers (ß = 0.237; P = 0.0067) and the test for trend was significant (P = 0.0161). Based on menopausal status, coffee drinking was associated with higher T-scores. Nevertheless, significant results were found only among premenopausal women (ß = 0.233; P = 0.0355 and ß = 0.234; P = 0.0152 for medium and high coffee drinking, respectively. The test for linear trend was significant (P = 0.0108). CONCLUSION: Coffee drinking was significantly associated with higher T-scores hence, a lower risk of osteoporosis in men and premenopausal women.

Effect of liquid ubiquinol supplementation on glucose, lipids and antioxidant capacity in type 2 diabetes patients: a double-blind, randomised, placebo-controlled trial.

Ubiquinone is a lipid antioxidant, and a novel liquid ubiquinol (a hydro-soluble, reduced form of coenzyme Q10) supplement was recently developed. The purpose of this study was to examine the levels of glucose, lipids and antioxidant capacity of type 2 diabetes patients after liquid ubiquinol supplementation. This study was designed as a randomised, double-blind, placebo-controlled trial. In all, fifty participants were randomly assigned to a placebo (n 25) or liquid ubiquinol (100 mg/d, n 25) group, and the intervention lasted for 12 weeks. Plasma coenzyme Q10, glucose homoeostasis parameters, lipid profiles, oxidative stress and antioxidative enzyme activities were measured during the study. After 12 weeks of supplementation, glyco Hb (HbA1c) value was significantly decreased in the liquid ubiquinol group (P=0·03), and subjects in the liquid ubiquinol group had significantly lower anti-glycaemic medication effect scores (MES) compared with those in the placebo group (P=0·03). The catalase (P<0·01) and glutathione peroxidase (P=0·03) activities were increased significantly after supplementation. Plasma coenzyme Q10 was correlated with the insulin level (P=0·05), homoeostatic model assessment-insulin resistance (P=0·07), quantitative insulin sensitivity check index (P=0·03) and the anti-hyperglycaemic agents' MES (P=0·03) after supplementation. Lipid profiles did not change after supplementation; however, the subjects in the placebo group had a significantly lower level of HDL-cholesterol after 12 weeks of intervention. In conclusion, oral intake of 100 mg/d liquid ubiquinol might benefit type 2 diabetes patients by increasing antioxidant enzyme activity levels, reducing HbA1c levels and maintaining HDL-cholesterol levels.

Effects of L-carnitine supplementation on lipid profiles in patients with coronary artery disease.

BACKGROUND: L-carnitine (LC) plays an important physiologic role in lipid metabolism. To date, no clinical study has been performed to examine the effect of LC supplementation on the lipid status of coronary artery disease (CAD) patients. The aim of this study was to investigate the lipid lowering effects of LC supplementation (1000 mg/d) in CAD patients. METHODS: CAD patients were identified by cardiac catheterization as having at least 50 % stenosis of one major coronary artery. Forty-seven subjects were recruited and randomly assigned to the placebo (n = 24) and to the LC (n = 23) groups. The intervention was administered for 12 weeks. The levels of LC, lipid profiles, and antioxidant enzyme activity (superoxide dismutase, SOD) were measured. RESULTS: The subjects in the LC group had significantly higher SOD activity (20.7 ± 4.2 versus 13.1 ± 2.9 U/mg of protein, P < 0.01), high density lipoprotein-cholesterol (1.34 ± 0.42 vs. 1.16 ± 0.24 mmol/L, HDL-C, P = 0.03), and apolipoprotein-A1 (Apo-A1, 1.24 ± 0.18 vs. 1.12 ± 0.13 g/L, P = 0.02) than those in the placebo group at week 12. Triglyceride (TG) level was slightly significantly reduced (1.40 ± 0.74 vs. 1.35 ± 0.62 mmol/L, P = 0.06) and the level of LC was negatively correlated with TG and apolipoprotein-B (Apo-B), and positively correlated with HDL-C and Apo-A1 after LC supplementation. Additionally, SOD activity was significantly negatively correlated with lipid profiles (total cholesterol, TG, and Apo-B) after supplementation. CONCLUSION: LC supplementation at a dose of 1000 mg/d showed significantly increased in HDL-C and Apo-A1 levels and a slight decrease in TG levels but no other changes in other lipids in CAD patients, and this lipid-lowering effect may be related to its antioxidant ability. Further studies should be conducted to define an optimal dose of LC for lipid-lowering in patients with CAD. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01819701.

Characterization and safety evaluation of a Deinococcus member as feed additive for hens.

As previous studies mainly focus on understanding the mechanisms of radioresistance in Deinococcus bacteria, the present study aimed at characterizing and verifying the safety use of the GKB-Aid 1995 strain, a member of the radiation-resistant bacterial genus Deinococcus, as an ingredient in feed supplements. Using Vitek 2 system and 16S rRNA gene sequencing, GKB-Aid 1995 most resembles Deinococcus grandis. The Ames test, in vitro chromosomal test, in vivo micronucleus test and acute toxicity test were performed subsequently for its safety evaluation. As there is a possibility that the pigment of GKB-Aid 1995 can pass from feed to eggs intended for human consumption, an acute toxicity test was also carried out in pigmented egg yolk. The results confirmed that GKB-Aid 1995 was non-genotoxic in three genotoxicity experiments, and the LD50 of GKB-Aid 1995 and the pigmented egg yolk in ICR mice was greater than 10 and 12 g kg(-1) body weight, respectively. Overall, these data indicate that GKB-Aid 1995 is a non-toxic substance with no genotoxicity and is therefore safe to be used as a feed supplement or feed additive. This study suggests there is potential in developing GKB-Aid 1995 as an animal feed additive intended to enhance yolk coloration to meet the demand of consumers.

Comparing the metabolism of quercetin in rats, mice and gerbils.

PURPOSE: Several species of rodents are used to investigate the metabolism of quercetin in vivo. However, it is unclear whether they are a proper animal model. Thus, we compared the metabolism of quercetin in Wistar rats (rats), Balb/c mice (mice) and Mongolian gerbils (gerbils). METHODS: We determined the levels of quercetin metabolites, quercetin-3-glucuronide (Q3G), quercetin-3'-sulfate (Q3'S) and methyl-quercetin isorhamnetin (IH), in the plasma, lungs and livers of three species of animals by high-performance liquid chromatography after acute and/or chronic quercetin administration. The metabolic enzyme activities in the intestinal mucosal membrane and liver were also investigated. RESULTS: First, we found that after acute quercetin administration, the Q3'S level was the highest in gerbils. However, after long-term supplementation (20 weeks), Q3G was the dominant metabolite in the plasma, lungs and livers followed by IH and Q3'S in all animals, although the gerbils still had a higher Q3'S conversion ratio. The average concentrations of total quercetin concentration in the plasma of gerbils were the highest in both short- and long-term studies. The activities of uridine 5'-diphosphate-glucuronosyltransferase, phenolsulfotransferase and catechol-O-methyltransferase were induced by quercetin in a dose- and tissue-dependent manner in all animals. CONCLUSIONS: Taken together, in general, after long-term supplementation the metabolism of quercetin is similar in all animals and is comparable to that of humans. However, the accumulation of quercetin and Q3'S conversion ratio in gerbils are higher than those in the other animals.

18-carbon polyunsaturated fatty acids ameliorate palmitate-induced inflammation and insulin resistance in mouse C2C12 myotubes.

Skeletal muscle is a major site of insulin action. Intramuscular lipid accumulation results in inflammation, which has a strong correlation with skeletal muscle insulin resistance (IR). The aim of this study was to explore the effects of linoleic acid, alpha-linolenic acid, and gamma-linolenic acid (GLA), 18-carbon polyunsaturated fatty acids (PUFAs), on palmitic acid (PA)-induced inflammatory responses and IR in C2C12 myotubes. Our data demonstrated that these three test 18-carbon PUFAs can inhibit PA-induced interleukin-6 and tumor necrosis factor-α messenger RNA (mRNA) expression and IR as evidenced by increases in phosphorylated AKT and the 160-kD AKT substrate, mRNA and plasma membrane protein expression of glucose transporter 4, and glucose uptake. Moreover, the 18-carbon PUFAs blocked the effects of PA on activation of mitogen-activated protein kinases (MAPKs), protein kinase C-θ (PKC-θ), AMP-activated protein kinase (AMPK) and nuclear factor-κB (NF-κB). Of note, supplementation with GLA-rich borage oil decreased proinflammatory cytokine production and hindered the activation of MAPKs, PKC-θ and NF-κB in the skeletal muscles of diabetic mice. The 18-carbon PUFAs did not reverse PA-induced inflammation or IR in C2C12 myotubes transfected with a constitutively active mutant IκB kinase-ß plasmid, which suggests the importance of the inhibition of NF-κB activation by the 18-carbon PUFAs. Moreover, blockade of AMPK activation by short hairpin RNA annulled the inhibitory effects of the 18-carbon PUFAs on PA-induced IR but not inflammation. Our findings suggest that the 18-carbon PUFAs may be useful in the management of PA-induced inflammation and IR in myotubes.

Antiinflammatory effects of L-carnitine supplementation (1000 mg/d) in coronary artery disease patients.

OBJECTIVE: Inflammation mediators have been recognized as risk factors for the pathogenesis of coronary artery disease (CAD). The purpose of this study was to investigate the effect of L-carnitine supplementation (LC, 1000 mg/d) on inflammation markers in patients with CAD. METHODS: We enrolled 47 patients with CAD in the study. The patients with CAD were identified by cardiac catheterization as having <50% stenosis of one major coronary artery. The patients were randomly assigned to the placebo (n = 24) and LC (n = 23) groups and the intervention was administered for 12 wk. The levels of LC, antioxidant status (malondialdehyde and antioxidant enzymes activities), and inflammation markers (C-reactive protein [CRP], interleukin [IL]-6, and tumor necrosis factor [TNF]-α) were measured. RESULTS: Thirty-nine participants completed the study (19 placebo; 20 LC). After LC supplementation, the levels of inflammation markers were significantly reduced compared with the baseline (CRP, P < 0.01; IL-6, P = 0.03; TNF-α, P = 0.07) and those in the placebo group (CRP, P < 0.05; IL-6, P = 0.04; TNF-α, P = 0.03). The levels of inflammation markers were significantly negatively correlated with the levels of LC and antioxidant enzymes activities (P < 0.05). CONCLUSIONS: We suggest that LC supplementation, due to its antioxidant effects, may have potential utility to reduce inflammation in CAD.

Effects of L-carnitine supplementation on oxidative stress and antioxidant enzymes activities in patients with coronary artery disease: a randomized, placebo-controlled trial.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Higher oxidative stress may contribute to the pathogenesis of coronary artery disease (CAD). The purpose of this study was to investigate the effect of L-carnitine (LC, 1000 mg/d) on the markers of oxidative stress and antioxidant enzymes activities in CAD patients. METHODS: We enrolled 47 CAD patients in the study. The CAD patients were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery. The subjects were randomly assigned to the placebo (n = 24) and LC (n = 23) groups. The intervention was administered for 12 weeks. The levels of serum LC, plasma malondialdehyde (MDA), and erythrocyte antioxidant enzymes activities [catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx)] were measured before and after intervention. RESULTS: Thirty-nine subjects completed the study (placebo, n = 19; LC, n = 20). After 12 weeks of LC supplementation, the level of MDA was significantly reduced (2.0 ± 0.3 to 1.8 ± 0.3 µmol/L, P = 0.02) and the level of LC (33.6 ± 13.6 to 40.0 ± 12.0 µmol/L, P = 0.04) and antioxidant enzymes activities [CAT (12.7 ± 5.5 to 13.1 ± 5.8 U/mg of protein, P = 0.02), SOD (14.8 ± 2.9 to 20.7 ± 5.8 U/mg of protein, P < 0.01), and GPx (20.3 ± 3.4 to 23.0 ± 3.1 U/mg of protein, P = 0.01)] were significantly increased. The level of LC was significantly positively correlated with the antioxidant enzymes activities (CAT, ß = 0.87, P = 0.02; SOD, ß = 0.72, P < 0.01). CONCLUSION: LC supplementation at a dose of 1000 mg/d was associated with a significant reduction in oxidative stress and an increase in antioxidant enzymes activities in CAD patients. CAD patients might benefit from using LC supplements to increase their anti-oxidation capacity. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01819701.

Formulated extract from multiple citrus peels impairs dendritic cell functions and attenuates allergic contact hypersensitivity.

It has been reported that gold lotion (GL), a formulated product made from the peels of six citrus fruits, has many pharmacological properties, such as anti-tumor, antioxidant, and anti-inflammatory activities. In this study, we investigated the immunomodulatory effect of GL on lipopolysaccharide (LPS) stimulated mouse bone marrow-derived DC maturation and function. Our experimental results have shown that GL significantly impaired the pro-inflammatory cytokine and chemokine secretion, suppressed the expression of major histocompatibility complex class I/II and costimulatory molecules (CD40, CD80 and CD86), increased phagocytic capacity, and reduced propensity to stimulate the autologous CD4(+) and CD8(+) T cell proliferation of LPS-induced DCs. Furthermore, we found that oral administration of GL attenuated the 2,4-Dinitro-1-fluorobenzene induced contact hypersensitivity (CHS) in animal models. Subsequently, our molecular mechanism studies showed that GL interfered with LPS-induced MAPK-JNK, p38 phosphorylation and nuclear translocation of NF-κB p65. In an essence, these findings are the first report to provide new insight in the immunopharmacological role of GL in terms of its effects on DC.

Neuronal effects of 4-t-Butylcatechol: a model for catechol-containing antioxidants.

Many herbal medicines and dietary supplements sold as aids to improve memory or treat neurodegenerative diseases or have other favorable effects on the CNS contain a catechol or similar 1,2-dihydroxy aromatic moiety in their structure. As an approach to isolate and examine the neuroprotective properties of catechols, a simple catechol 4-t-Butylcatechol (TBC) has been used as a model. In this study, we investigated the effects of TBC on lipopolysaccharide (LPS)-activated microglial-induced neurotoxicity by using the in vitro model of coculture murine microglial-like cell line HAPI with the neuronal-like human neuroblastoma cell line SH-SY5Y. We also examined the effects of TBC on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. TBC at concentrations from 0.1-10 microM had no toxic effect on HAPI cells and SH-SY5Y cells, and it inhibited LPS (100 ng/ml)-induced increases of superoxide, intracellular ROS, gp91(Phox), iNOS and a decrease of HO-1 in HAPI cells. Under coculture condition, TBC significantly reduced LPS-activated microglia-induced dopaminergic SH-SY5Y cells death. Moreover, TBC (0.1-10 microM) inhibited 6-OHDA-induced increases of intracellular ROS, iNOS, nNOS, and a decrease of mitochondria membrane potential, and cell death in SH-SY5Y cells. However, the neurotoxic effects of TBC (100 microM) on SH-SY5Y cells were also observed including the decrease in mitochondria membrane potential and the increase in COX-2 expression and cell death. TBC-induced SH-SY5Y cell death was attenuated by pretreatment with NS-398, a selective COX-2 inhibitor. In conclusion, this study suggests that TBC might possess protective effects on inflammation- and oxidative stress-related neurodegenerative disorders. However, the high concentration of TBC might be toxic, at least in part, for increasing COX-2 expression.

Intake levels and major food sources of energy and nutrients in the Taiwanese elderly.

The purpose of this article is to examine dietary intake levels and major food sources of energy and nutrients for the Taiwanese elderly in order to relate nutrient intakes to food choices and to provide suggestions for dietary improvement. The data were derived from the 24-hour recalls from 1,911 subjects (955 males and 956 females) aged 65 and above, who participated in the Elderly NAHSIT carried out from 1999 to 2000. The differences in food consumption patterns between the elderly and younger adults (aged 19 to 64) were also evaluated by comparison with data obtained from NAHSIT 1993-1996. The results revealed that cereals/roots, meat, other protein-rich foods and fats/oils contributed most to daily energy intake. The energy contributions from fats/oils, poultry, meat, other protein-rich foods, refreshments/snacks, alcoholic beverages, and miscellaneous food groups were lower in elderly diets compared with those of younger adults. Meat and cereals/roots were the major food sources of protein. The main carbohydrate-contributing food group was cereals/roots, while primary lipid sources were meat and fats/oils for the elderly. The food groups with a high contribution to vitamin intake were the following: vegetables for vitamin A; meat and cereals/roots for vitamin B1; dairy products, vegetables, cereals/roots and meat for vitamin B2; cereals/roots, seafood and meat for niacin; meat, vegetables and cereals/roots for vitamin B6; plant oils for vitamin E; and vegetables and fruit for vitamin C. The highest ranked food sources for minerals are listed as follows: dairy products, vegetables and seafood for calcium; dairy products and cereals/roots for phosphorous; vegetables and meat for iron; and vegetables, cereals/ roots, other protein-rich foods and seafood for magnesium. The elderly were found to consume more salt, dairy products and vegetables, but less poultry and meat than their younger counterparts. In summary, differences in consumption patterns between the elderly and younger adults was reflected in differences in common food sources of energy and specific nutrients. The dietary patterns of the elderly are in general "healthier" than that of younger adults except for higher salt intake among the elderly. Nonetheless, our elderly population needs to increase their intake of calcium, magnesium, vitamins E and B6, and dietary fiber, and decrease their consumption of salt. Promoting the ingestion of whole-grain and nut products may be a useful strategy to improve the nutritional status of the Taiwanese elderly, aiming at increasing the percentage of energy obtained from carbohydrates and the daily intake of vitamins E and B6, magnesium, and dietary fiber. Suitable strategies are also needed to improve the calcium status of Taiwanese elderly, particularly as a high proportion of them are either lactose intolerant or dislike dairy products.

Vitamin E status and its dietary determinants in Taiwanese--results of the Nutrition and Health Survey in Taiwan 1993-1996.

BACKGROUND: A large proportion of Taiwanese are considered to have inadequate vitamin E intake according to Taiwanese RDA. AIM OF THE STUDY: To evaluate the vitamin E status in Taiwan using biochemical indicators, and to examine the influences of dietary factors. METHODS: The Nutrition and Health Survey in Taiwan 1993-1996 was conducted using a multi-stage sampling scheme. Data of 3614 subjects (1728 males, and 1886 females) aged 4 years and above were included in the current analysis. RESULTS: Females had higher levels of serum alpha-tocopherol than males. Serum level of alpha-tocopherol significantly increased with age and blood lipids (p < 0.001). The prevalence rate of deficiency, assessed by the ratio of serum alpha-tocopherol to cholesterol+triglyceride(TG) < 1.59 micromol/mmol, was 1.4 % for Taiwanese aged 4 and above. The prevalence was 1.02 % for adults. This biochemical profile was superior in women compared to men. The age-serum vitamin E status was U-shaped, being poorest in teenagers. Geographical variation in vitamin E/cholesterol+TG ratio was not apparent across regions. An association was observed between serum vitamin E status and frequency of vitamin E supplements, fresh fruits, and 100 % fruit juices. An association was also seen with dietary intakes of vitamin C and vitamin E assessed by 24-hour recall. CONCLUSION: The prevalence rate of vitamin E deficiency in Taiwan was low. An association was observed between serum vitamin E status and dietary vitamins E and C intakes either from foods or supplements.