Guangdong Provincial Key Laboratory of Food

Guangzhou, China

Guangdong Provincial Key Laboratory of Food

Guangzhou, China
Time filter
Source Type

Wang D.,Sun Yat Sen University | Xia M.,Sun Yat Sen University | Yan X.,Sun Yat Sen University | Li D.,Sun Yat Sen University | And 6 more authors.
Circulation Research | Year: 2012

Rationale: We and others have demonstrated that anthocyanins have antiatherogenic capability. Because intact anthocyanins are absorbed very poorly, the low level of circulating parent anthocyanins may not fully account for their beneficial effect. We found recently that protocatechuic acid (PCA), a metabolite of cyanidin-3 to 0-β-glucoside (Cy-3-G), has a remarkable antiatherogenic effect. Objective:: To investigate whether mouse gut microbiota metabolizes Cy-3-G into PCA and to determine whether and how PCA contributes to the antiatherogenic potency of its precursor, Cy-3-G. Methods and Results: PCA was determined as a gut microbiota metabolite of Cy-3-G in ApoE mice, verified by the utilization of antibiotics to eliminate gut microbiota and further microbiota acquisition. PCA but not Cy-3-G at physiologically reachable concentrations promoted cholesterol efflux from macrophages and macrophage ABCA1 and ABCG1 expression. By conducting a miRNA microarray screening, we revealed that expression of miRNA-10b in macrophages can be reduced by PCA. Functional analyses demonstrated that miRNA-10b directly represses ABCA1 and ABCG1 and negatively regulates cholesterol efflux from murine-and human-derived macrophages. Further in vitro and ex vivo analyses verified that PCA accelerates macrophage cholesterol efflux, correlating with the regulation of miRNA-10b-ABCA1/ABCG1 cascade, whereas Cy-3-G consumption promoted macrophage RCT and regressed atherosclerotic lesion in a gut microbiotaendependent manner. Conclusions:: PCA, as the gut microbiota metabolite of Cy-3-G, exerts the antiatherogenic effect partially through this newly defined miRNA-10b-ABCA1/ ABCG1-cholesterol efflux signaling cascade. Thus, gut microbiota is a potential novel target for atherosclerosis prevention and treatment. © 2012 American Heart Association, Inc.

Li D.,Guangdong Provincial Key Laboratory of Food | Li D.,Sun Yat Sen University | Zhang Y.,Sun Yat Sen University | Liu Y.,Guangdong Provincial Key Laboratory of Food | And 5 more authors.
Journal of Nutrition | Year: 2015

Background: Oxidative stress plays an essential role in the pathogenesis of type 2 diabetes. Anthocyanin, a natural antioxidant, has been reported to reduce oxidative stress and to attenuate insulin resistance and diabetes in animal models; however, the translation of these observations to humans has not been fully tested. Objective: This study was designed to investigate the effects of purified anthocyanins on dyslipidemia, oxidative status, and insulin sensitivity in patients with type 2 diabetes. Methods: A total of 58 diabetic patients were given 160 mg of anthocyanins twice daily or placebo (n = 29/group) for 24 wk in a randomized, placebo-controlled, double-blind trial. Participants and investigators were masked to treatment allocation. Results: Anthocyanin supplementation significantly decreased serum LDL cholesterol (by 7.9%; P < 0.05), triglycerides (by 23.0%; P < 0.01), apolipoprotein (apo) B-48 (by 16.5%; P < 0.05), and apo C-III (by 11.0%; P < 0.01) and increased HDL cholesterol (by 19.4%; P < 0.05) compared with placebo after the 24-wk intervention. In addition, patients in the anthocyanin group showed higher total radical-trapping antioxidant parameter and ferric ion reducing antioxidant power values than did patients in the placebo group (both P < 0.05). Serum concentrations of 8-iso-prostaglandin F2a, 13-hydroxyoctadecadienoic acid, and carbonylated proteins in patients in the anthocyanin group were significantly less than in patients in the placebo group (23.4%, 25.8%; P<0.01 and 20%; P = 0.022, respectively). Furthermore, supplementationwith anthocyanin lowered fasting plasma glucose (by 8.5%; P < 0.05) and homeostasis model assessment for insulin resistance index (by 13%; P < 0.05), and elevated serum adiponectin (by 23.4%; P < 0.01) and b-hydroxybutyrate (by 42.4%; P = 0.01) concentrations compared with placebo supplementation. Conclusion: These findings demonstrate that anthocyanin supplementation exerts beneficial metabolic effects in subjects with type 2 diabetes by improving dyslipidemia, enhancing antioxidant capacity, and preventing insulin resistance. This trial was registered at as NCT02317211. © 2015 American Society for Nutrition.

Guo H.,Guangdong Provincial Key Laboratory of Food | Guo H.,Shaoguan University | Li D.,Guangdong Provincial Key Laboratory of Food | Ling W.,Guangdong Provincial Key Laboratory of Food | And 2 more authors.
Journal of Lipid Research | Year: 2011

Mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) controls the fi rst step of triacylglycerol (TAG) synthesis and is critical to the understanding of chronic metabolic disorders such as primary nonalcoholic fatty liver disease (NAFLD). Anthocyanin, a large group of polyphenols, was negatively correlated with hepatic lipid accumulation, but its impact on mtGPAT1 activity and NAFLD has yet to be determined. Hepatoma cell lines and KKAy mice were used to investigate the impact of anthocyanin on high glucose-induced mtGPAT1 activation and hepatic steatosis. Treatment with anthocyanin cyanidin-3-O-β-glucoside (Cy-3-g) reduced high glucose-induced GPAT1 activity through the prevention of mtGPAT1 translocation from the endoplasmic reticulum to the outer mitochondrial membrane (OMM), thereby suppressing intracellular de novo lipid synthesis. Cy-3-g treatment also increased protein kinase C ζ phosphorylation and membrane translocation in order to phosphorylate the mtF0F1-ATPase β -subunit, reducing its enzymatic activity and thus inhibiting mtGPAT1 activation. In vivo studies further showed that Cy-3-g treatment signifi cantly decreases hepatic mtGPAT1 activity and its presence in OMM isolated from livers, thus ameliorating hepatic steatosis in diabetic KKAy mice. Our fi ndings reveal a novel mechanism by which anthocyanin regulates lipogenesis and thereby inhibits hepatic steatosis, suggesting its potential therapeutic application in diabetes and related steatotic liver diseases. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.

Zhang Y.,General Hospital of Guangzhou Military Command | Qiu J.,General Hospital of Guangzhou Military Command | Wang X.,General Hospital of Guangzhou Military Command | Wang X.,Guangdong Provincial Key Laboratory of Food | And 6 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2011

Objective-Considerable evidence supports the early involvement of monocyte/macrophage recruitment to activated endothelial cells by leukocyte adhesion molecules during atherogenesis. AMP-activated protein kinase (AMPK) is highly expressed in vascular endothelial cells, but its impact on monocyte adhesion and the related mechanisms are not fully understood. The present study was designed to evaluate the impact of and gain mechanistic insight into the signaling coupling AMPK function to the antiinflammatory response. Methods and results-5-Aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR) treatment or overexpression of constitutively active AMPK markedly reduced human monocytic human acute monocytic leukemia cell line-1 cell adhesion and the expression of vascular cell adhesion molecule-1 in tumor necrosis factor-α-activated human aortic endothelial cells. Furthermore, AICAR or constitutively active AMPK overexpression strongly inhibited the histone acetyltransferase activity of the transcriptional coactivator p300 by phosphorylation of Ser89, which in turn decreased tumor necrosis factor-α-activated p300-mediated acetylation of nuclear factor-κB p65 on Lys221 and reduced the DNA binding activity of nuclear factor-κB by inhibiting its recruitment to its target gene promoters. AMPK phosphorylates the transcriptional coactivator p300 via the atypical protein kinase Cι/λ. Conclusion-Our findings demonstrate that transcriptional coactivator p300 phosphorylation at Ser89 by AMPK is critical for the therapeutic effect of AMPK and may be a potential target for pharmaceutical intervention in inflammatory diseases such as atherosclerosis. © 2011 American Heart Association, Inc.

Wang D.,Sun Yat Sen University | Wei X.,Sun Yat Sen University | Yan X.,Sun Yat Sen University | Jin T.,Sun Yat Sen University | And 3 more authors.
Journal of Agricultural and Food Chemistry | Year: 2010

Polyphenols, including anthocyanins, from various plant foods are effective in the prevention of atherosclerosis in animal and human studies. Protocatechuic acid (PCA), a major metabolite of anthocyanins, has been found to possess the anti-carcinogenic effect, whereas the in vivo effect of PCA as an anti-atherosclerotic agent remains unknown. We demonstrated herein that PCA inhibited monocyte adhesion to tumor necrosis factor-α (TNF-α)-activated mouse aortic endothelial cells, associated with the inhibition of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression. Furthermore, PCA inhibited the nuclear content of p65, a subunit of nuclear factor-κB (NF-κB), along with reduced NF-κB binding activity. Finally, PCA administration in the apolipoprotein E (ApoE)-deficient mouse model reduced aortic VCAM-1 and ICAM-1 expression, NF-κB activity, and plasma-soluble VCAM-1 and ICAM-1 levels, with inhibiting atherosclerosis development. We suggest that PCA possesses the anti-atherogenic effect at least partially via its anti-inflammatory activity. © 2010 American Chemical Society.

Wang D.,Sun Yat Sen University | Zou T.,Sun Yat Sen University | Yang Y.,Sun Yat Sen University | Yan X.,Sun Yat Sen University | And 2 more authors.
Biochemical Pharmacology | Year: 2011

Polyphenols, including anthocyanins, from various plant foods are effective in reducing the severity of atherosclerosis in animal and human studies. Due to the poor understanding of the bioavailability of anthocyanins, the potential antiatherogenic mechanisms underlying the action remain largely unknown. Herein, we found that oral gavage of cyanidin-3-O-β-glucoside (Cy-3-G) could be transformed into protocatechuic acid (PCA), and the plasma maximal levels of Cy-3-G were 3.7-fold lower than that of PCA in the apolipoprotein E (ApoE)-deficient mice. Subsequently, we observed that PCA treatment has a higher capacity than Cy-3-G treatment in decreasing CC chemokine receptor 2 (CCR2) expression in the mouse peripheral blood monocytes (PBMs), along with reducing the mouse PBMs chemokine toward CC ligand-2 (CCL2) in a Boyden chamber. Interesting, in the ApoE-deficient mouse model, orally gavaged with Cy-3-G has a higher ability than gavaged with PCA to reduce CCR2 expression in PBMs. PBMs deprived from the Cy-3-G-treated ApoE-deficient mice have a lower ability than those from PCA-treated animals to migrate toward CCL2. Furthermore, as compared with the PCA group, Cy-3-G treatment more efficiently reduced thioglycollate-induced macrophage infiltration into the abdominal cavity. Thus, we suggest that Cy-3-G may reduce the monocyte infiltration in mice via down-regulation of CCR2 expression in monocytes, at least in part, with the aid of its metabolite PCA. These above data imply that the anti-monocyte/macrophage infiltration property of Cy-3-G and its metabolite PCA may be an important antiatherogenic mechanism for anthocyanins. © 2011 Published by Elsevier Inc.

Liu Y.,Guangdong Provincial Key Laboratory of Food | Liu Y.,Sun Yat Sen University | Wang D.,Sun Yat Sen University | Chen H.,Guangdong Provincial Key Laboratory of Food | And 3 more authors.
Atherosclerosis | Year: 2015

Objectives: This study was to examine the association between plasma retinol binding protein 4 (RBP4) levels and the complexity of angiographic coronary lesion in patients with coronary artery disease (CAD). Methods and results: A cross-sectional and prospective study was carried out in Guangzhou Chinese population. 672 persons were evaluated by medical history, clinical examination, coronary angiography, and fasting plasma samples, and were followed prospectively for 3 years. We measured the plasma RBP4 levels in 447 women (201 with stable CAD and 246 with acute coronary syndrome [ACS]). Coronary lesions were classified as having a simple or complex appearance based on the visual estimation of the coronary angiograms. Median plasma RBP4 levels were significantly higher in stable CAD patients with complex coronary lesions (n=84) than in those with simple lesions (n=117) (38.78[range 32.65-46.91] vs. 30.78 [range 24.48-36.08] μg/ml, P<0.001). Multiple logistic regression analysis demonstrated that higher RBP4 levels were independently associated with a 23% higher risk for complex lesions (odds ratio 1.228, 95% confidence interval [CI] 1.061 to 1.358; P=0.031). Among the ACS patients, who had higher RBP4 levels than the stable CAD patients, those with multiple complex lesions had significantly higher median RBP4 levels than those with a single complex lesion (46.47μg/ml [range 37.68-53.29] vs. 38.15μg/ml [range 32.26-44.56], P<0.001). Total plasma RBP4 levels were predictors of cardiac death (hazard ratio [HR]: 1.102; 95% CI: 1.086 to 1.191; P=0.012) after adjustment for traditional risk factors for CAD. Conclusion: Plasma RBP4 levels are significantly associated with coronary lesion complexity in women with stable CAD and ACS and predict incident cardiovascular events. © 2014 Elsevier Ireland Ltd.

Xia M.,Guangdong Provincial Key Laboratory of Food | Xia M.,Sun Yat Sen University | Liu Y.,Guangdong Provincial Key Laboratory of Food | Liu Y.,Sun Yat Sen University | And 6 more authors.
Hepatology | Year: 2013

Recent studies have revealed the essential role of retinol binding protein 4 (RBP4) in insulin resistance. However, the impact of RBP4 on aberrant lipogenesis, the common hepatic manifestation in insulin resistance states, and the underlying mechanism remain elusive. The present study was designed to examine the effect of RBP4 on sterol regulatory element-binding protein (SREBP-1) and hepatic lipogenesis. Treatment with human retinol-bound RBP4 (holo-RBP4) significantly induced intracellular triglyceride (TAG) synthesis in HepG2 cells and this effect is retinol-independent. Furthermore, RBP4 treatment enhanced the levels of mature SREBP-1 and its nuclear translocation, thereby increasing the expression of lipogenic genes, including fatty acid synthase (FAS), acetyl coenzyme A carboxylase-1 (ACC-1), and diacylglycerol O-acyltransferase 2 (DGAT-2). Stimulation of HepG2 cells with RBP4 strongly up-regulated the expression of transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β) at both the messenger RNA (mRNA) and protein levels. The transcriptional activation of PGC-1β is necessary and sufficient for the transcriptional activation of SREBP-1 in response to RBP4. The cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) was identified as the target transcription factor involved in the RBP4-mediated up-regulation of PGC-1β transcription as a result of phosphorylation on Ser133. Furthermore, in vivo RBP4 infusion induced SREBP-1c activation and consequently accelerated hepatic lipogenesis and plasma TAG in C57BL/6J mice, a phenomenon not observed in Ppargc1b knockout mice. Conclusion: These findings reveal a novel mechanism by which RBP4 achieves its effects on hepatic lipid metabolism. © 2013 American Association for the Study of Liver Diseases.

Guo H.,Shaoguan University | Ling W.,Guangdong Provincial Key Laboratory of Food
Reviews in Endocrine and Metabolic Disorders | Year: 2015

With the dramatically increasing prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide, there is an urgent need for new strategies to combat the growing epidemic of these metabolic diseases. Diet is an essential factor affecting the development of and risk for obesity and T2DM and it can either help or hurt. In searching for preventative and therapeutic strategies, it is therefore advantageous to consider the potential of certain foods and their bioactive compounds to reverse or prevent the pathogenic processes associated with metabolic disease. Anthocyanins are naturally occurring polyphenolic compounds abundant in dark-colored fruits, vegetables and grains. Epidemiological studies suggest that increased consumption of anthocyanins lowers the risk of T2DM. Many in vitro and in vivo studies also reveal an array of mechanisms through which anthocyanins could prevent or reverse obesity- and T2DM-related pathologies including promotion of antioxidant and anti-inflammatory activities, improvement of insulin resistance, and hypolipidemic and hypoglycemic actions. Here, we summarize the data on anthocyanin-mediated protection against obesity and T2DM and the underlying mechanisms. Further population-based and long-term human intervention studies are necessary to ultimately evaluate the use of anthocyanins for protection/prevention against the development of obesity and T2DM. © 2015 Springer Science+Business Media New York

Zou T.-B.,Sun Yat Sen University | Wang M.,Sun Yat Sen University | Gan R.-Y.,Sun Yat Sen University | Ling W.-H.,Sun Yat Sen University | Ling W.-H.,Guangdong Provincial Key Laboratory of Food
International Journal of Molecular Sciences | Year: 2011

Mulberry is one of the most widely used traditional Chinese medicines. Anthocyanins are the main bioactive components of mulberry, and possess important biological activities, such as antimicrobial, anti-inflammatory and antioxidant activities. This study investigated the ultrasound-assisted extraction (UAE) of anthocyanins from mulberry by using response surface methodology (RSM). The extraction conditions associated with anthocyanin yield, including extraction solvent, liquid-to-solid rate, temperature and extraction time, are discussed. The optimal conditions obtained by RSM for UAE from mulberry include 63.8% methanol contains 1% (v/v) trifluoroacetic acid (TFA), 43.2 °C temperature, 23.8 (v/w) liquid-to-solid ratio, and 40 min time for the maximum yield (64.70 ± 0.45 mg/g). The results indicated that the UAE can be an effective method for the extraction of some active components from plant materials. © 2011 by the authors.

Loading Guangdong Provincial Key Laboratory of Food collaborators
Loading Guangdong Provincial Key Laboratory of Food collaborators