Bioanalysis
·
2025
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IF 1.8
Kaiwei Luo,Danrui Liu,Shengshuo Zhang,Xin Zhang,Qunan Cheng,Jie Lin,Yonghua Yu
Aims This study aimed to establish a robust LC-MS/MS method for quantifying trazodone in human plasma and investigate its pharmacokinetic profile in healthy Chinese subjects under fasting and fed conditions.Materials & methods A validated LC-MS/MS method using protein precipitation was applied to analyze trazodone in 68 healthy subjects (34 fasting/34 fed), with full method validation performed.Results This method exhibited high selectivity, precision, and accuracy. The results showed good linearity in the range of 5–3000 ng/mL and matrix effect results showed no matrix interference. The pharmacokinetic data revealed notable differences between the fasting and postprandial states.Conclusions The validated LC-MS/MS method proved reliable for trazodone quantification. The observed food effects on absorption suggest clinical dosing should consider administration conditions to ensure optimal therapeutic outcomes.
研究领域:
分析化学
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药理学
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临床医学
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DOI
PubMed
高影响因子
Marine Drugs
·
2020
·Vol. 18
·期 9
·444
·
IF 4.073
Bin Wei,Qi-Wu Zhong,Song-Ze Ke,Tao-Shun Zhou,Qiao-Li Xu,Si-Jia Wang,Jian-Wei Chen,Hua-Wei Zhang,Wei-Hua Jin,Hong Wang
A low fasting blood glucose level is a common symptom in diabetes patients and can be induced by high-fat diet (HFD) feeding at an early stage, which may play important roles in the development of diabetes, but has received little attention. In this study, five polysaccharides were prepared fromSargassumfusiformeand their effects on HFD-induced fasting hypoglycemia and gut microbiota dysbiosis were investigated. The results indicated that C57BL/6J male mice fed an HFD for 4 weeks developed severe hypoglycemia and fourSargassumfusiformepolysaccharides (SFPs), consisting of Sf-2, Sf-3, Sf-3-1, and Sf-A, significantly prevented early fasting hypoglycemia without inducing hyperglycemia. Sf-1 and Sf-A could also significantly prevent HFD-induced weight gain. Sf-2, Sf-3, Sf-3-1, and Sf-A mainly attenuated the HFD-induced decrease in Bacteroidetes, and all five SFPs had a considerable influence on the relative abundance ofOscillospira,Mucispirillum, andClostridiales. Correlation analysis revealed that the fasting blood glucose level was associated with the relative abundance ofMucispinllumandOscillospira. Receiver operating characteristic analysis indicated thatMucispinllumandOscillospiraexhibited good discriminatory power (AUC = 0.745–0.833) in the prediction of fasting hypoglycemia. Our findings highlight the novel application of SFPs (especially Sf-A) in glucose homeostasis and the potential roles ofMucispinllumandOscillospirain the biological activity of SFPs.Keywords:Sargassum fusiformepolysaccharides;high-fat diet;gut microbiota;early fasting hypoglycemia
研究领域:
营养学
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微生物学
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代谢病研究
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DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
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IF 4.5
Yue Gao,Binbin Huang,Yunyi Qin,Bing Qiao,Mengfei Ren,Liqing Cao,Yan Zhang,Maozhen Han
Background: Obesity and high fasting blood glucose (FBG) resulting from high-fat diets (HFDs) have emerged as significant public health concerns, garnering increasing attention. Recently, gut microbiota has been linked with metabolic diseases such as type 2 diabetes (T2DM), and its mediating role in dietary supplements has been confirmed. Seeking various dietary supplements to lose body weight (BW) and decrease FBG and explaining the underlying mechanism have become the research hotspots in T2DM studies.Methods: In this study, rutin and proanthocyanidins (PA) were selected as dietary supplements (200 mg/kg × day, oral gavage, 6 weeks) in T2DM mice induced with HFD to assess their efficacy in weight loss, FBG reduction, gut microbiota alterations, and the associated underlying mechanisms.Results: Our findings indicate that rutin was more effective than PA in relieving inflammation and fat hypertrophy, although both significantly reduced BW and FBG within 2 weeks after the intervention. Analysis of 16S rRNA amplicons revealed substantial alterations in the gut microbial community composition of mice administered with PA and rutin compared to HFD-fed mice. Importantly, several core microbes, particularly a series of probiotics, such as Akkermansia, Lactococcus, Odoribacter, Faecalibaculum, and Roseburia were identified, which were significantly correlated with the changes in BW and FBG.Conclusion: Overall, our study highlights that rutin and PA can reduce BW, FBG, and inflammation by modulating the gut microbiota composition, providing novel perspectives for managing and treating weight and FBG concerns in obesity and T2DM patients through dietary supplements in clinical treatment.
研究领域:
营养学
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微生物学
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代谢疾病研究
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DOI
PubMed
高影响因子
DRUGS IN R&D
·
2024
·
IF 2.2
Jia Caiyun,Zhao Na,Song Haojing,Hu Yiting,Xu Yufang,Guo Caihui,Bai Wanjun,Dong Zhanjun
Background Ondansetron is a highly selective 5-HT3 receptor antagonist that alleviates nausea and vomiting. Bioequivalence evaluation ensures that the efficacy of generic drugs is consistent with that of the original drug. Objective The objective of this study was to evaluate the bioequivalence of ondansetron hydrochloride (HCl) tablets taken in single doses under fasting and postprandial conditions in healthy subjects. Methods In this randomized, open-label, two-cycle, crossover phase I study, liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) was used to determine the ondansetron concentration in dipotassium-ethylenediaminetetraacetate (K 2 -EDTA) plasma after the subjects received a single 8 mg of ondansetron and reference formulation. Twenty-six healthy subjects received one tablet of ondansetron under fasting conditions and 28 subjects received one under postprandial conditions. Bioequivalence was established if the 90% confidence interval (CI) was 80.00–125.00%. The pharmacokinetic parameters were calculated via WinNonLin 8.1 software and the bioequivalence data were evaluated via Phoenix WinNonlin 8.1 statistics software. Results The geometric mean ratio (GMR) of the maximum observed concentration ( C max ), the area under the plasma concentration‒time curve (AUC) from time zero to the last sampling time (AUC 0– t ), and the AUC from time zero to infinity (AUC 0–∞ ) from the test/reference formulation under fasting conditions were 90.50, 90.43, and 90.25, respectively. The 90% CIs were 83.75–97.79, 82.64–98.95, and 82.25–99.03, respectively. The GMRs of C max , AUC 0– t , and AUC 0–∞ after a high-fat meal were 96.85, 93.57, and 93.77, respectively; the 90% CIs were 88.43–106.07, 87.35–100.24, and 87.35–100.68, respectively. Conclusion The test and reference formulations of ondansetron HCl have bioequivalence for healthy adult subjects under fasting and postprandial conditions.
研究领域:
药理学
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临床药学
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DOI
PubMed
高影响因子
RAPID COMMUNICATIONS IN MASS SPECTROMETRY
·
2020
·Vol. 34
·期 12
·e8779
·
IF 2.2
Jianglan Long,Liwei Liu,Qingquan Jia,Zhirui Yang,Zhi Sun,Can Yan,Dan Yan
Rationale The prevalence of type 2 diabetes mellitus (T2DM) is increasing but its early diagnosis in high risk populations remains challenging using only fasting blood glucose (FBG) or hemoglobin A1c measurements. It is, therefore, important to search for an integrated biomarker for early diagnosis by determining metabolites associated with the progression of the disease. Methods We recruited 149 participants (51 T2DM patients, 50 individuals with impaired fasting glucose (IFG) and 48 normal glucose tolerance subjects). Their serum samples were analyzed based on a metabolomics approach using ultra-high-performance liquid chromatography quadrupole-Orbitrap high-resolution accurate mass spectrometry (UHPLC/Q-Orbitrap HRMS). The changes in metabolites were profiled and evaluated using univariate and multivariate analyses. Furthermore, a biomarker model was established and the potential biomarkers were evaluated using binary logistic regression analysis and receiver operating characteristic analysis with AUC (area under the curve). Pathway analysis of differential metabolites was performed to reveal the important biological information. Results Thirty-eight differential metabolites were identified as significantly associated with T2DM patients and 23 differential metabolites with IFG individuals, mainly amino acids, carnitines, and phospholipids. By evaluating 17 potential biomarkers, we defined a novel integrated biomarker consisting of 2-acetolactate, 2-hydroxy-2,4-pentadienoate, L-arabinose and L-glutamine. The AUCs of the integrated biomarker with IFG and T2DM patients were 0.874 and 0.994, respectively, which showed a superior diagnostic performance. The levels of 2-acetolactate and 2-hydroxy-2,4-pentadienoate were strongly positively correlated with FBG, while L-glutamine and L-arabinose were strongly negatively associated with FBG. After pathway analysis, it was suggested that the majority of the influenced metabolic pathways associated with diabetes referred to amino acid metabolism. Conclusions The integrated biomarker could diagnose IFG and T2DM with a superior diagnostic performance. This finding provides support for novel biomarkers in the diagnosis and treatment of diabetes.
研究领域:
医学
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代谢组学
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生物信息学
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DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2024
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IF 10.3
Danyang Zhang,Weigao Zhang,Hu Liu,Shuxian Huang,Wangchao Huang,Yunfeng Zhu,Xuening Ma,Yugui Xia,Jianfa Zhang,Wei Lu,Da Shao,Dan Weng
Environmental chemicals and pollutants are increasingly recognized for their potential transgenerational effects. Acetyl tributyl citrate (ATBC), a widely used plasticizer substituting di-(2-ethylhexyl) phthalate (DEHP), was identified as an inducer of lipogenesis in male mice by our previous research. This study aimed to investigate the impact of ATBC exposure on the metabolic homeostasis of female mice and simultaneously evaluate its intergenerational effects. Female C57BL/6J mice were orally exposed to ATBC (0.01 or 1 μg/kg/day) for 10 weeks before mating with unexposed male mice. The resulting F1 female mice were bred with unexposed males to generate F2 offspring. Our results indicated that 10-week ATBC exposure disrupted glucose metabolism homeostasis and the reproductive system in F0 female mice. In F1 female mice, elevated liver lipid levels and mild insulin resistance were observed. In the F2 generation, maternal ATBC exposure resulted in increased weight gain, elevated liver triglycerides, and higher fasting blood glucose levels, primarily in F2 male mice. These findings suggest that maternal ATBC exposure may exert intergenerational disturbing effects on glucose metabolism across generations of mice. Further investigation is needed to evaluate the health risks associated with ATBC exposure.
研究领域:
环境健康
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毒理学
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代谢
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生殖生物学
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DOI
PubMed
高影响因子
ACS Omega
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2020
·
IF 2.87
Yilong Liu,Xianan Zhang,Liuhuan Zhan,Chang Xu,Linxiao Sun,Huamin Jiang,Chongde Sun,Xian Li
The present study is to investigate the polyphenolic composition and in vivo antidiabetic effect of white-fleshed Chinese bayberry cultivar “Shui Jing”. By liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS), 38 polyphenols were identified in the Shui Jing fruit extract (SJE), where proanthocyanidins (PAs), including epigallocatechin gallate (EGCG), as well as flavonols, including myricitrin and quercetrin, were the predominant ingredients. After a 5-week experiment, the SJE (200 mg/kg bodyweight) significantly reduced fasting blood glucose, elevated glucose tolerance, and insulin sensitivity in diabetic KK-Ay mice. It markedly attenuated bodyweight gain and decreased glycolipid metabolism-related markers including insulin, leptin, glucagon, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and alanine aminotransferase (ALT) levels in mice. Liver weight and hepatic lipid accumulation were also significantly reduced by the SJE. Gene expressions of insulin 1 (INS1) and glycogen synthase kinase 3 β (GSK3b) were markedly inhibited while the hepatic phosphorylation of AMPKα was significantly increased in the liver of SJE-treated mice, indicating that the SJE may exert an antidiabetic effect through an AMPK-dependent pathway. In conclusion, white bayberry rich in PAs and flavonols may have great potential in the regulation of diabetes mellitus.
研究领域:
药理学
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营养学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2023
·
IF 2.65
Lei Zhang,Ming-yue Pan,Tao Li,Zhi-min Jin,Zhu Liu,Qiu-yue Liu,Yong Liu,Jia-yuan Ding,Huan Jiang,Xingchen Hou
Quercetin was extracted from Portulaca oleracea L. through biphasic acid hydrolysis to investigate its potential as a suppressor of dipeptidyl peptidase IV (DPP-IV) and its hypoglycemic effect in type 2 diabetic mice. The extraction procedure was optimized utilizing the response surface method (RSM) in a single-factor experimental setting. An extraction efficiency of 0.675% was achieved using the following optimized parameters: 0.064 mol/L vitriol, 1 : 109.155 solid-liquid ratio, and 21.408 min ultrasonication. Overall, findings indicate the effectiveness of quercetin extraction. A mouse model for type 2 diabetes was established to receive oral treatment with various quercetin concentrations for 8 weeks. Fasting blood glucose (FBG) and the DPP-IV activity in the serum were significantly reduced. The weight and insulin levels of the mice in the quercetin group were raised compared to those in the model group ( < 0.01). Quercetin dose-dependently inhibited postprandial blood glucose excursions, as demonstrated by the oral glucose tolerance test. These results confirmed that quercetin has hypoglycemic effects and considerably improves insulin sensitivity via DPP-IV targeting.
研究领域:
药理学
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生物化学
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糖尿病研究
·
植物化学
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2017
·
IF 3.144
Hai Zhang,Shengsheng Zhang,Li Wang,Xiaofei Liu,Yuntang Wu
Previous results from our laboratory showed that chitosan biguanidine hydrochloride (CSGH) and chitooligosaccharide guanidine (COSG) could control glucose uptake by regulating the expression of glucose transporters (GLUTs) in vitro experiments. In this study, we try to delineate changes observed in activation of diacylglycerol (DAG)/protein kinase C- β (PKC- β ) pathway and GLUT2 in kidney. STZ-induced diabetic rats were administered COSG via daily intra-gastric gavage for 8 weeks. Obviously, COSG significantly attenuated fasting blood glucose and blood glucose level by modulating the over-expression of GLUT2 and the level of DAG as well. Immunohistological examination revealed that factors such as PKC- β and transforming growth factor- β (TGF- β ) diminished to various extents after treatment with COSG, which impinged on the synthesis of extracellular matrix (ECM) components like fibronectin (FN). As a result, high glucose-induced activation of DAG/PKC pathway is inhibited, which is associated with the concentration of glucose controlled by the expression of GLUT2 with the treatment of COSG.
研究领域:
药理学
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糖尿病研究
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肾病学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Xiaoqian Wang,Lichun Guo,Libing Zheng,Wei Zhao,Li Li
Noncaloric or low-caloric sweeteners have become popular worldwide, although debates persist regarding their impact on health. To investigate whether the sweeteners are favorable for glucose homeostasis, our study assessed the effects of glycyrrhetinic acid monoglucuronide (GAMG) and several commonly used sweeteners [glycyrrhetinic acid (GA), stevioside, erythritol, sucralose, and aspartame] on glycometabolism and elucidated the underlying mechanisms. The C57BL/6J male mice were exposed to different sweeteners for 10 weeks, and our results showed that GAMG significantly reduced fasting blood glucose (FBG) levels (FBG-control: 3.81 ± 0.42 mmol/L; FBG-GAMG: 3.37 ± 0.38 mmol/L; p < 0.05) and the blood glucose levels 15 and 30 min after sucrose or maltose loading (p < 0.05). Furthermore, it improved glucose tolerance (p = 0.028) and enhanced insulin sensitivity (p = 0.044), while the other sweeteners had negligible or adverse effects on glucose homeostasis. Subsequent experiments showed that GAMG inhibited α-glucosidases potently (IC50 = 0.879 mg·mL–1), increased three SCFA-producing bacteria and SCFAs levels (p < 0.05), and promoted the gene expression of SCFA receptor GPR43 (p = 0.018). These results suggest that GAMG may regulate blood glucose by inhibiting α-glucosidases and modulating gut microbial SCFAs. Our findings prove that GAMG, beneficial to blood glucose regulation, is a promising natural sweetener for future utilization.
研究领域:
营养学
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内分泌学
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药理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2015
·
IF 3.028
Jing Sun,Xueqi Fu,Ye Liu,Yongsen Wang,Bo Huo,Yidi Guo,Xuefeng Gao,Wannan Li,Xin Hu
Background Honokiol is one of the main bioactive constituents of the traditional Chinese herbal drug Magnolia bark (Cortex Magnoliae officinalis , Hou Po). The aim of this study was to probe its anti-type 2 diabetes mellitus effects and the underlying mechanism. Methods Type 2 diabetic mouse model was established by intraperitoneally injecting with streptozotocin. Fasting blood glucose, body weight, and lipid profile were measured. The subcutaneous adipose tissue, skeletal muscle, and liver were isolated as well as homogenized. The phospho-insulin receptor β-subunit (IRβ), IRβ, phospho-AKT, AKT, phospho-ERK1/2, ERK1/2, phosphotyrosine, and actin were examined by Western blot assay. Cell viability or cytotoxicity was analyzed by using MTT method. The inhibitory potencies of honokiol on the protein tyrosine phosphatase 1B (PTP1B) activity were performed in reaction buffer. Molecular docking and dynamic simulation were also analyzed. Results In in vivo studies, oral treatment with 200 mg/kg honokiol for 8 weeks significantly decreases the fasting blood glucose in type 2 diabetes mellitus mice. The phosphorylations of the IRβ and the downstream insulin signaling factors including AKT and ERK1/2 significantly increase in adipose, skeletal muscle, and liver tissue of the honokiol-treated mice. Moreover, honokiol enhanced the insulin-stimulated phosphorylations of IRβ, AKT, and ERK1/2 in a dose-dependent manner in C2C12 myotube cells. Meanwhile, honokiol enhanced insulin-stimulated GLUT4 translocation. Importantly, honokiol exhibited reversible competitive inhibitory activity against PTP1B with good selectivity in vitro and in vivo. Furthermore, using molecular docking and dynamic simulation approaches, we determined the potential binding mode of honokiol to PTP1B at an atomic level. Conclusion These findings indicated the hypoglycemic effects of honokiol and its mechanism that honokiol improved the insulin sensitivity by targeting PTP1B. Therefore, our study may highlight honokiol as a promising insulin sensitizer for the therapy of type 2 diabetes.
研究领域:
药理学
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内分泌学
·
分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
REJUVENATION RESEARCH
·
2020
·Vol. 23
·期 5
·367-376
·
IF 0
Mei Wang,Shan-Quan Chang,Yu-Shan Tian,Ge-Qiang Zhang,Jin Qi
The incidence of type 2 diabetes mellitus (T2DM) has been increasing in recent years and has become a serious threat to human health. Zengye Decoction (ZYD), a well-known traditional Chinese medicinal formula, has been used in the treatment of T2DM with yin asthenia and extreme heat since Qing Dynasty. However, the characteristics of antidiabetic activities of ZYD have not been fully elucidated. In our study, high-fat diet and streptozotocin were used to establish the T2DM rat model. After 3 weeks of treatment with ZYD, the fasting blood glucose (FBG), oral glucose tolerance, the fasting serum insulin concentration, insulin sensitivity index (ISI), serum lipid profiles, and pancreas histopathology were measured. Then, under circumstance of insulin-resistant glucose consumption, 2-(N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake and glycogen content in C2C12 myotubes, 3T3-L1 adipocytes, and HepG2 cells were determined, respectively. Finally, the expressions of key targets in the insulin signaling pathway were measured to explain the potential mechanism underlying these activities. After administration with ZYD, a notable reduction in FBG levels, oral glucose tolerance test-area under the curve, blood lipid metabolism, and ISI values were observed compared with the diabetic control group. Moreover, ZYD restored the damaged islet cells in T2DM rats. Significant increases in glucose consumption, glucose uptake, glycogen content, expression of glucose transporter type 4, and the ratio of p-Akt/Akt were observed in the ZYD groups. According to the above results, ZYD exhibited glucose disposal, including glucose consumption, glucose uptake, and glycogen content and promoted the Akt signal pathway, which indicates that ZYD exerts significant hypoglycemic effect in T2DM.
研究领域:
药理学
·
内分泌学
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中医
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产品关联
DOI
PubMed
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