Xing-Ping Dai

Preparative isolation and purification of seven main antioxidants from Eucommia ulmoides Oliv. (Du-zhong) leaves using HSCCC guided by DPPH-HPLC experiment

Seven antioxidants were purified from Eucommia ulmoides Oliv. leaves using HSCCC guided by DPPH-HPLC experiment. HSCCC was successfully used to separate target antioxidants by three runs with different solvent systems after D101 column chromatography fractionation. Ethyl acetate-n-butanol-water (1:2:3, v/v/v) was selected as the optimum solvent system to purify geniposidic acid. Ethyl acetate-ethanol-water (4:1:5, v/v/v) was used to isolate caffeic acid, chlorogenic acid and ferulic acid. While three flavonoids, quercetin-3-O-sambubioside, rutin and isoquercitrin were purified by petroleum ether-ethyl acetate-methanol-water (1:5:1:5, v/v/v/v). The structures were identified by MS and NMR. Antioxidant activities were assessed, and compounds 2-7 showed strong antioxidant activities. This is the first report about separation of antioxidants from E. ulmoides leaves by HSCCC. The results indicated that the combinative methods using DPPH-HPLC and HSCCC could be widely applied for screening and isolation of antioxidants from complex extracts.

IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population

AbstractAim:To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus (T2DM) and the repaglinide therapeutic efficacy in Chinese T2DM patients.Methods:A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment.Results:The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls (P<0.05 and P<0.001, respectively). The effects of the repaglinide treatment on FPG (P<0.05) and PPG (P<0.05) were reduced in patients with the rs1470579 AC+CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT+TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS (P<0.01) compared with GG genotype subjects.Conclusion:The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients.

Effects of the Peroxisome Proliferator Activated Receptor‐γ Coactivator‐1α (PGC‐1α) Thr394Thr and Gly482Ser Polymorphisms on Rosiglitazone Response in Chinese Patients With Type 2 Diabetes Mellitus

The objective was to investigate whether peroxisome proliferator activated receptor‐γ coactivator‐1α (PGC‐1α) Thr394Thr and Gly482Ser polymorphisms influence rosiglitazone response in Chinese patients with type 2 diabetes mellitus. Among the 241 patients enrolled in genotyping for PGC‐1α Thr394Thr and Gly482Ser polymorphisms by polymerase chain reaction‐restriction fragment length polymorphism assay, 41 patients with different Thr394Thr or Gly482Ser genotypes received oral rosiglitazone (4 mg/d) for 12 consecutive weeks. Carriers of A allele of Thr394Thr had high density lipoprotein‐cholesterol that was enhanced to a lesser degree and smaller attenuated postprandial serum insulin compared with G alleles (P < .05), and patients with PGC‐1α Gly482Gly had fasting plasma glucose that was attenuated to a greater degree (P < .01) and postprandial serum insulin (P < .05) compared with Gly482Ser+Ser482Ser. After rosiglitazone treatment, carriers of A allele of Thr394Thr and Ser allele of Gly482Ser showed a trend in worsening for GG (P < .05) and a significant therapeutic response to rosiglitazone for Gly/Gly (P < .05). These data suggest that the PGC‐1α Thr394Thr and Gly482Ser polymorphisms are associated with therapeutic efficacy of multiple‐dose rosiglitazone in Chinese patients with type 2 diabetes mellitus.

KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese Type 2 diabetic patients

The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895 polymorphisms on repaglinide efficacy in Chinese patients with Type 2 diabetes mellitus (T2DM). In all, 367 T2DM patients and 214 controls were genotyped. Forty of the T2DM patients were randomly selected to undergo 8 weeks repaglinide treatment. The frequency of the rs2237892 allele was lower in the T2DM patients than in the control group (P < 0.05). The frequency of the rs2237895 C allele was higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic patients with the rs2237892 risk C allele had lower fasting insulin levels (P < 0.01) and homeostasis model assessment of insulin resistance (HOMA‐IR; P < 0.01) values than carriers of the T allele. Diabetic patients with the rs2237895 risk C allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose (PPG) levels (P < 0.01) and HOMA‐IR values (P < 0.01) than those with the A allele. Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes. In conclusion, KCNQ1 rs2237892 and rs2237895 polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.

NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes

AIMS We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day(-1)). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment. RESULTS The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P < 0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1) , P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1), P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (-2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1), P < 0.01) (-3.53, -1.84 vs.-1.99, -0.13) and postprandial plasma glucose (-6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1), P < 0.01) (-9.28, -4.62 vs.-4.34, -0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (-6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1), P < 0.05) (-8.20, -4.89 vs.-3.92, -1.20). CONCLUSIONS The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.

NAMPT -3186C/T polymorphism affects repaglinide response in Chinese patients with Type 2 diabetes mellitus

1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)‐3186 C/T and ‐948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients.

The protective effect of magnesium lithospermate B against glucose-induced intracellular oxidative damage

OBJECTIVES To investigate the effects of magnesium lithospermate B (LAB) on intracellular reactive oxygen species (ROS) production induced by high dose of glucose or H(2)O(2), we explored the influences of LAB on the expression of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf2) in HEK293T cells after treatment with high dose of glucose. MATERIALS AND METHODS The total nuclear proteins in HEK293T cells were extracted with Cytoplasmic Protein Extraction Kit. The ROS level was determined by flow cytometry. The mRNA and protein expression of HO-1 and Nrf2 were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. RESULTS LAB reduced the ROS production in HEK293T cells cultured under oxidative stress. High dose of glucose enhanced the expression of HO-1 mRNA and HO-1 protein in a time-dependent manner. LAB enhanced the expression of HO-1 mRNA and HO-1 protein in a dose-dependent manner treated with high dose of glucose. The amount of Nrf2 translocation was enhanced after cells were pretreated with 50μmol/L or 100μmol/L LAB. Silencing of Nrf2 gene eliminated the enhanced expression of HO-1 protein induced by high dose of glucose plus LAB. CONCLUSIONS LAB plays an important role against glucose-induced intracellular oxidative damage. The enhanced expression of HO-1 mRNA and HO-1 protein caused by LAB is regulated via Nrf2 signal pathway.

Serine racemase rs391300 G/A polymorphism influences the therapeutic efficacy of metformin in Chinese patients with diabetes mellitus type 2.

1. The aim of this study was to investigate the association of the serine racemase (SRR) rs391300 G/A polymorphism with the risk of diabetes mellitus type 2 (T2DM) and to assess the impacts of the polymorphism on the therapeutic efficacy of metformin in Chinese patients.

The genetic polymorphisms of β3-adrenergic receptor (AR) Trp64Arg and β2-AR Gln27Glu are associated with obesity in Chinese male hypertensive patients

Abstract Background: Genetic polymorphisms of β3-adrenergic receptor (AR) Trp64Arg and β2-AR Gln27Glu may result in significant change in the functions of these receptors. The aims of the present study were to investigate the association between Trp64Arg, Arg16Gly and Gln27Glu polymorphisms and the susceptibility to obesity and hypertension in a Chinese population. Methods: A total of 437 Chinese subjects including 149 obese hypertensive patients, 139 non-obese essential hypertensive patients, and 149 non-obese normotensive healthy controls were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific (AS)-PCR assays were used to identify Trp64Arg, Arg16Gly, and Gln27Glu genotypes. Results: The allele frequencies of 64Arg and 27Glu in the obese hypertensive group were 0.178 and 0.128, respectively. Both were significantly higher than in the non-obese hypertensive and the control groups (p<0.05). Further analysis showed that this association existed only in male hypertensive patients. Conclusions: These data reveal that frequencies of β3-AR 64Arg and β2-AR 27Glu were significantly higher in our obese hypertensive patients than in the non-obese hypertensive population and healthy controls. β3-AR Trp64Arg and β2-AR Gln27Glu genetic polymorphisms are associated with obesity in Chinese male hypertensive patients. Clin Chem Lab Med 2007;45:493–8.

Hollow porous ionic liquids composite polymers based solid phase extraction coupled online with high performance liquid chromatography for selective analysis of hydrophilic hydroxybenzoic acids from complex samples

Polar and hydrophilic properties of hydroxybenzoic acids usually made them coelute with interferences in high performance liquid chromatography (HPLC) analysis. Then selective analysis of them was necessary. Herein, hollow porous ionic liquids composite polymers (PILs) based solid phase extraction (SPE) was firstly fabricated and coupled online with HPLC for selective analysis of hydroxybenzoic acids from complex matrices. Hollow porous PILs were firstly synthesized using Mobil Composition of Matter No. 48 (MCM-48) spheres as sacrificial support, 1-vinyl-3-methylimidazolium chloride (VMIM+Cl-) as monomer, and ethylene glycol dimethacrylate (EGDMA) as cross-linker. Various parameters affecting synthesis, adsorption and desorption behaviors were investigated and optimized. Steady-state adsorption studies showed the resulting hollow porous PILs exhibited high adsorption capacity, fast adsorption kinetics, and excellent specific adsorption. Subsequently, the application of online SPE system was studied by selective analysis of protocatechuic acid (PCA), 4-hydroxybenzoic acid (4-HBA), and vanillic acid (VA) from Pollen Typha angustifolia. The obtained limit of detection (LOD) varied from 0.002 to 0.01μg/mL, the linear range (0.05-5.0μg/mL) was wide with correlation coefficient (R) from 0.9982 to 0.9994, and the average recoveries at three spiking levels ranged from 82.7 to 102.4%, with column-to-column relative standard deviation (RSD) below 8.1%. The proposed online method showed good accuracy, precision, specificity and convenience, which opened up a universal and efficient route for selective analysis of hydroxybenzoic acids from complex samples.