Junkuan Wang

Antihypertensive effects and mechanisms of chlorogenic acids

Chlorogenic acids (CGAs) are potent antioxidants found in certain foods and drinks, most notably in coffee. In recent years, basic and clinical investigations have implied that the consumption of chlorogenic acid can have an anti-hypertension effect. Mechanistically, the metabolites of CGAs attenuate oxidative stress (reactive oxygen species), which leads to the benefit of blood-pressure reduction through improved endothelial function and nitric oxide bioavailability in the arterial vasculature. This review article highlights the physiological and biochemical findings on this subject and highlights some remaining issues that merit further scientific and clinical exploration. In the framework of lifestyle modification for the management of cardiovascular risk factors, the dietary consumption of CGAs may hold promise for providing a non-pharmacological approach for the prevention and treatment of high blood pressure.

Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials

BACKGROUNDnPrevious studies suggest that L-arginine, an amino acid and a substrate of nitric oxide synthase, may have blood pressure (BP)-lowering effect. Because some studies were performed with limited number of patients with hypertension and therefore limited statistical power with sometimes inconsistent results, we aimed to examine the effect of oral L-arginine supplementation on BP by conducting a meta-analysis of randomized, double-blind, placebo-controlled trials.nnnMETHODSnPubMed, Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov databases were searched through June 2011 to identify randomized, double-blind, placebo-controlled trials of oral L-arginine supplementation on BP in humans. We also reviewed reference lists of obtained articles. Either a fixed-effects or, in the presence of heterogeneity, a random-effects model was used to calculate the combined treatment effect.nnnRESULTSnWe included 11 randomized, double-blind, placebo-controlled trials involving 387 participants with oral L-arginine intervention ranging from 4 to 24 g/d. Compared with placebo, L-arginine intervention significantly lowered systolic BP by 5.39 mm Hg (95% CI -8.54 to -2.25, P = .001) and diastolic BP by 2.66 mm Hg (95% CI -3.77 to -1.54, P < .001). Sensitivity analyses restricted to trials with a duration of 4 weeks or longer and to trials in which participants did not use antihypertensive medications yielded similar results. Meta-regression analysis suggested an inverse, though insignificant (P = .13), relation between baseline systolic BP and net change in systolic BP.nnnCONCLUSIONSnThis meta-analysis provides further evidence that oral L-arginine supplementation significantly lowers both systolic and diastolic BP.

Mitochondrial Dysfunction in Obesity-Associated Nonalcoholic Fatty Liver Disease: The Protective Effects of Pomegranate with Its Active Component Punicalagin

AIMSnPunicalagin (PU) is one of the major ellagitannins found in the pomegranate (Punica granatum), which is a popular fruit with several health benefits. So far, no studies have evaluated the effects of PU on nonalcoholic fatty liver disease (NAFLD). Our work aims at studying the effect of PU-enriched pomegranate extract (PE) on high fat diet (HFD)-induced NAFLD.nnnRESULTSnPE administration at a dosage of 150u2009mg/kg/day significantly inhibited HFD-induced hyperlipidemia and hepatic lipid deposition. As major contributors to NAFLD, increased expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukins 1, 4, and 6 as well as augmented oxidative stress in hepatocytes followed by nuclear factor (erythroid-derived-2)-like 2 (Nrf2) activation were normalized through PE supplementation. In addition, PE treatment reduced uncoupling protein 2 (UCP2) expression, restored ATP content, suppressed mitochondrial protein oxidation, and improved mitochondrial complex activity in the liver. In contrast, mitochondrial content was not affected despite increased peroxisomal proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and elevated expression of genes related to mitochondrial beta-oxidation after PE treatment. Finally, PU was identified as the predominant active component of PE with regard to the lowering of triglyceride and cholesterol content in HepG2 cells, and both PU- and PE-protected cells from palmitate induced mitochondrial dysfunction and insulin resistance.nnnINNOVATIONnOur work presents the beneficial effects of PE on obesity-associated NAFLD and multiple risk factors. PU was proposed to be the major active component.nnnCONCLUSIONSnBy promoting mitochondrial function, eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of NAFLD.

Enhanced bioavailability of zeaxanthin in a milk-based formulation of wolfberry (Gou Qi Zi; Fructus barbarum L.)

The carotenoid zeaxanthin is concentrated within the macula. Increased macular zeaxanthin is suggested to lower the risk of age-related macular degeneration. The small red berry, wolfberry (Fructus barbarum L.; Gou Qi Zi and Kei Tze), is one of the richest natural sources of zeaxanthin. However, carotenoid bioavailability is low, and food-based products with enhanced bioavailability are of interest. The present study investigated zeaxanthin bioavailability from three wolfberry formulations. Berries were homogenised in hot (80 degrees C) water, warm (40 degrees C) skimmed milk and hot (80 degrees C) skimmed milk, with freeze drying of each preparation into a powdered form. A zeaxanthin-standardised dose (15 mg) of each was consumed, in randomised order, together with a standardised breakfast by twelve healthy, consenting subjects in a cross-over trial, with a 3-5-week washout period between treatments. Blood samples were taken via a venous cannula immediately before (fasting) and 2, 4, 6, 7, 8 and 10 h post-ingestion. Zeaxanthin concentration in the triacylglycerol-rich lipoprotein fraction of plasma was measured by HPLC. Results showed that triacylglycerol-rich lipoprotein zeaxanthin peaked at 6 h post-ingestion for all formulations. Zeaxanthin bioavailability from the hot milk formulation was significantly higher (P < 0.001) than from the others. Mean area under the curve (n 12) results were 9.73 (sem 2.45), 3.24 (sem 0.72) and 3.14 (sem 1.09) nmol x h/l for the hot milk, warm milk and hot water formulations, respectively. Results showed clearly that homogenisation of wolfberry in hot skimmed milk results in a formulation that has a 3-fold enhanced bioavailability of zeaxanthin compared with both the classical hot water and warm skimmed milk treatment of the berries.

Goji berry effects on macular characteristics and plasma antioxidant levels.

Purpose. Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. Methods. This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. Results. The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. Conclusions. Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.

Effect of probiotic fermented milk on blood pressure: a meta-analysis of randomised controlled trials

Previous studies have suggested that probiotic fermented milk may possess blood pressure (BP)-lowering properties. In the present study, we aimed to systematically examine the effect of probiotic fermented milk on BP by conducting a meta-analysis of randomised controlled trials. PubMed, Cochrane library and the ClinicalTrials.gov databases were searched up to March 2012 to identify eligible studies.The reference lists of the obtained articles were also reviewed. Either a fixed-effects or a random-effects model was used to calculate the combined treatment effect. Meta-analysis of fourteen randomised placebo-controlled trials involving 702 participants showed that probiotic fermented milk, compared with placebo, produced a significant reduction of 3·10 mmHg (95% CI 24·64, 21·56) in systolic BP and 1·09 mmHg (95% CI 22·11, 20·06) in diastolic BP. Subgroup analyses suggested a slightly greater effect on systolic BP in hypertensive participants than in normotensive ones (23·98 v. 22·09 mmHg). Analysis of trials conducted in Japan showed a greater reduction than those conducted in European countries for both systolic BP (26·12 v. 22·08 mmHg) and diastolic BP (23·45 v. 20·52 mmHg). Some evidence of publication bias was present, but sensitivity analysis excluding small trials that reported extreme results only affected the pooled effect size minimally. In summary, the present meta-analysis suggested that probiotic fermented milk has BP-lowering effects in pre-hypertensive and hypertensive subjects.

Pre-pregnancy BMI, gestational weight gain and postpartum weight retention: a meta-analysis of observational studies

OBJECTIVEnTo determine the association of gestational weight gain (GWG) or pre-pregnancy BMI with postpartum weight retention (PPWR).nnnDESIGNnMeta-analysis.nnnSETTINGnPubMed, Cochrane Controlled Trials Register, EMBASE, Science Citation Index Expanded, Current Contents Connects and Biosis Previews were used to search articles.nnnSUBJECTSnPublications that described the influence of pre-pregnancy BMI or GWG on PPWR.nnnRESULTSnSeventeen studies that satisfied the eligibility criteria were included in the analyses. Women with inadequate and excessive GWG had significantly lower mean PPWR of -2·14 kg (95 % CI -2·43, -1·85 kg) and higher PPWR of 3·21 kg (95 % CI 2·79, 3·62 kg), respectively, than women with adequate GWG. When postpartum time spans were stratified into 1-3 months, 3-6 months, 6-12 months, 12-36 months and ≥15 years, the association between inadequate GWG and PPWR faded over time and became insignificant (-1·42 kg; 95 % CI -3·08, 0·24 kg) after ≥15 years. However, PPWR in women with excess GWG exhibited a U-shaped trend; that is, a decline during the early postpartum time span (year 1) and then an increase in the following period. Meta-analysis of qualitative studies showed a significant relationship between excessive GWG and higher PPWR risk (OR=2·08; 95 % CI 1·60, 2·70). Moreover, meta-analysis of pre-pregnancy BMI on PPWR indicated that mean PPWR decreased with increasing BMI group.nnnCONCLUSIONSnThese findings suggest that GWG, rather than pre-pregnancy BMI, determines the shorter- or longer-term PPWR.

Immunomodulatory Effects of Dietary Supplementation with a Milk-Based Wolfberry Formulation in Healthy Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial

Wolfberry (fruit of Lycium barbarum) has been prized for many years in China for its immunomodulatory property and its high specific antioxidant content. However, clear clinical evidence demonstrating the effect of wolfberry dietary supplementation is still lacking. After our earlier report showing that a proprietary milk-based wolfberry formulation (Lacto-Wolfberry) enhances in vivo antigen-specific adaptive immune responses in aged mice, the present study aimed at demonstrating the effect of dietary Lacto-Wolfberry supplementation on immune functions in the elderly, especially vaccine response known to decline with aging. A 3-month randomized, double-blinded, placebo-controlled study was conducted on 150 healthy community-dwelling Chinese elderly (65-70 years old) supplemented with Lacto-Wolfberry or placebo (13.7 grams/day). Immune response to influenza vaccine was assessed in the study, along with inflammatory and physical status. No serious adverse reactions were reported during the trial, neither symptoms of influenza-like infection. No changes in body weight and blood pressure, blood chemistry or cells composition, as well as autoantibodies levels were observed. The subjects receiving Lacto-Wolfberry had significantly higher postvaccination serum influenza-specific immunoglobulin G levels and seroconversion rate, between days 30 and 90, compared with the placebo group. The postvaccination positive rate was greater in the Lacto-Wolfberry group compared to the placebo group, but did not reach statistical significance. Lacto-Wolfberry supplementation had no significant effect on delayed-type hypersensitivity response and inflammatory markers. In conclusion, long-term dietary supplementation with Lacto-Wolfberry in elderly subjects enhances their capacity to respond to antigenic challenge without overaffecting their immune system, supporting a contribution to reinforcing immune defense in this population.

Bitter Gourd Inhibits the Development of Obesity-Associated Fatty Liver in C57BL/6 Mice Fed a High-Fat Diet

Bitter gourd (BG) is a popular fruit in Asia with numerous well-known medicinal uses, including as an antidiabetic. In the current study, we aimed to explore the effects of BG on mitochondrial function during the development of obesity-associated fatty liver. C57BL/6 mice were divided into 4 experimental groups: mice fed a normal diet (control; included for reference only), mice fed a high-fat diet (HFD), and mice fed an HFD supplemented with freeze-dried BG powder through daily gavage at doses of 0.5 (HFD+0.5BG) and 5 (HFD+5BG) g/kg, respectively. After 16 wk, mice in the HFD+5BG group showed less body and tissue weight gain and less hyperglycemia and hyperlipidemia compared with those in the HFD group (P < 0.05). In both HFD+0.5BG and HFD+5BG groups, serum interleukin-6 concentration was lower than that in the HFD group (P < 0.02). The serum C-reactive protein concentration was lower in the HFD+5BG group compared with the HFD group (P < 0.04). An analysis of liver tissue revealed lower liver triglyceride and cholesterol concentrations in both HFD+0.5BG and HFD+5BG groups than in the HFD group (P < 0.01). The HFD+5BG group had less activation of the sterol regulatory element binding protein/fatty acid synthase (SREBP-1/FAS) pathway, greater superoxide dismutase activity, and less total protein and mitochondrial protein oxidation than did the HFD group (P < 0.05). Mitochondrial complex I, II, III, and V activity was greater in the HFD+0.5BG group than in the HFD group (P < 0.03). The HFD+5BG group only had greater complex V activity compared with the HFD group (P < 0.05). Mitochondrial dynamics regulators, including dynamin related protein 1 (DRP1) and mitofusin 1 (MFN1), as well as proapoptotic protein expression levels were restored by BG treatment (P < 0.02). Taken together, our results suggest that BG prevents inflammation and oxidative stress, modulates mitochondrial activity, suppresses apoptosis activation, and inhibits lipid accumulation during the development of fatty liver.

A Milk-Based Wolfberry Preparation Prevents Prenatal Stress-Induced Cognitive Impairment of Offspring Rats, and Inhibits Oxidative Damage and Mitochondrial Dysfunction In Vitro

Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl2/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.