Metabolite profiles of ginsenosides Rk1 and Rg5 in zebrafish using ultraperformance liquid chromatography/quadrupole–time-of-flight MS

AbstractBackgroundIn the present study, metabolite profiles of ginsenosides Rk1 and Rg5 from red ginseng or red notoginseng in zebrafish were qualitatively analyzed with ultraperformance liquid chromatography/quadrupole–time-of-flight MS, and the possible metabolic were pathways proposed.MethodsAfter exposing to zebrafish for 24 h, we determined the metabolites of ginsenosides Rk1 and Rg5. The chromatography was accomplished on UPLC BEH C18 column using a binary gradient elution of 0.1% formic acetonitrile–0.1% formic acid water. The quasimolecular ions of compounds were analyzed in the negative mode. With reference to quasimolecular ions and MS2 spectra, by comparing with reference standards and matching the empirical molecular formula with that of known published compounds, and then the potential structures of metabolites of ginsenosides Rk1 and Rg5 were acquired.ResultsFour and seven metabolites of ginsenoside Rk1 and ginsenoside Rg5, respectively, were identified in zebrafish. The mechanisms involved were further deduced to be desugarization, glucuronidation, sulfation, and dehydroxymethylation pathways. Dehydroxylation and loss of C-17 residue were also metabolic pathways of ginsenoside Rg5 in zebrafish.ConclusionLoss of glucose at position C-3 and glucuronidation at position C-12 in zebrafish were regarded as the primary physiological processes of ginsenosides Rk1 and Rg5

Utilizing machine learning algorithms for the prediction of carotid artery plaques in a Chinese population

Background: Ischemic stroke is a significant global health issue, imposing substantial social and economic burdens. Carotid artery plaques (CAP) serve as an important risk factor for stroke, and early screening can effectively reduce stroke incidence. However, China lacks nationwide data on carotid artery plaques. Machine learning (ML) can offer an economically efficient screening method. This study aimed to develop ML models using routine health examinations and blood markers to predict the occurrence of carotid artery plaques.Methods: This study included data from 5,211 participants aged 18–70, encompassing health check-ups and biochemical indicators. Among them, 1,164 participants were diagnosed with carotid artery plaques through carotid ultrasound. We constructed six ML models by employing feature selection with elastic net regression, selecting 13 indicators. Model performance was evaluated using accuracy, sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), F1 score, kappa value, and Area Under the Curve (AUC) value. Feature importance was assessed by calculating the root mean square error (RMSE) loss after permutations for each variable in every model.Results: Among all six ML models, LightGBM achieved the highest accuracy at 91.8%. Feature importance analysis revealed that age, Low-Density Lipoprotein Cholesterol (LDL-c), and systolic blood pressure were important predictive factors in the models.Conclusion: LightGBM can effectively predict the occurrence of carotid artery plaques using demographic information, physical examination data and biochemistry data

Comparative Study on the Pharmacokinetics of Rutin and Quercetin in Diabetic and Normal Rats by HPLC-DAD

Diabetes mellitus (DM) is a serious health problem affecting millions of individuals worldwide. It is showed that some changes of many enzymes and transporters concerned with metabolism and disposal of drug have taken place in organism under pathologic state of DM. The pharmacokinetic of drug should be different between diabetic and normal animals. Rutin and quercetin can also be used to treatment of diabetic mellitus. So, this paper investigated the difference of pharmacokinetic profiles of rutin and quercetin in diabetic and normal rats in vivo by HPLC-DAD method. The pharmacokinetic parameters were analyzed by double-compartmental method (DAS2.0). The pharmacokinetic parameters of rutin in normal and diabetic rats were: (22.203 ± 2.6) and (36.174 ± 7.5) mg · h/L for AUC(0-4); (0.726 ± 0.13) and (1.069 ± 0.17) h for MRT(0-4), (5.413 ± 0.57) and (6.595 ± 0.38) h for t1/2; (0.424 ± 0.071) and (0.226 ± 0.072) L/h/kg for Cl, respectively. The pharmacokinetic parameters of quercetin in normal and diabetic rats were: (5.243 ± 0.82) and (2.376 ± 0.61) mg h/L for AUC(0-4); (2.556 ± 0.52) and (1.616 ± 0.35) h for MRT(0-4), (1.216 ± 0.17) and (0.992 ± 0.12) h for t1/2; (1.918 ± 0.32) and (4.342 ± 0.99) L/h/kg for Cl, respectively. Those results indicate that the pharmacokinetic profiles of rutin and quercetin were changed by DM.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Comparative study on the pharmacokinetic of lansoprazole in gastric ulcer and normal rabbits by HPLC-DAD

Gastric ulcer is one of ulcerous diseases and may result in some changes of many enzymes and transporters concerned with metabolism and disposal of drug. The pharmacokinetic of drug should be different between peptic ulcer and normal animals. Lansoprazole has been one of important medicine for treatment of ulcerous diseases. So, this paper investigated the difference of pharmacokinetic profiles of lansoprazole in gastric ulcer and normal rabbits in vivo by HPLC-DAD method. In this work, a liquid-liquid extraction and enrichment method with RP-HPLC determination route was taken. The pharmacokinetic parameters were analyzed by double-compartmental method (DAS2.0). The pharmacokinetic parameters of lansoprazole in normal and ulcer rabbits were as follows: (614.42 ± 152.25) and (875.73 ± 316.34) mg h/L for AUC(0-6.5); (0.68 ± 0.12) and (0.83 ± 0.22) h for MRT(0-6.5), (0.52 ± 0.23) and (0.87 ± 0.42) h for t1/2 ; (6.13 ± 2.11) and (2.54 ± 1.65) L/h/kg for CL, respectivelyGastric ulcer is one of ulcerous diseases and may result in some changes of many enzymes and transporters concerned with metabolism and disposal of drug. The pharmacokinetic of drug should be different between peptic ulcer and normal animals. Lansoprazole has been one of important medicine for treatment of ulcerous diseases. So, this paper investigated the difference of pharmacokinetic profiles of lansoprazole in gastric ulcer and normal rabbits in vivo by HPLC-DAD method. In this work, a liquid-liquid extraction and enrichment method with RP-HPLC determination route was taken. The pharmacokinetic parameters were analyzed by double-compartmental method (DAS2.0). The pharmacokinetic parameters of lansoprazole in normal and ulcer rabbits were as follows: (614.42 ± 152.25) and (875.73 ± 316.34) mg h/L for AUC(0-6.5); (0.68 ± 0.12) and (0.83 ± 0.22) h for MRT(0-6.5 , (0.52 ± 0.23) and (0.87 ± 0.42) h for t1/2 ; (6.13 ± 2.11) and (2.54 ± 1.65) L/h/kg for CL, respectivelyColegio de Farmacéuticos de la Provincia de Buenos Aire

Probing the endosperm gene expression landscape in Brassica napus

<p>Abstract</p> <p>Background</p> <p>In species with exalbuminous seeds, the endosperm is eventually consumed and its space occupied by the embryo during seed development. However, the main constituent of the early developing seed is the liquid endosperm, and a significant portion of the carbon resources for the ensuing stages of seed development arrive at the embryo through the endosperm. In contrast to the extensive study of species with persistent endosperm, little is known about the global gene expression pattern in the endosperm of exalbuminous seed species such as crucifer oilseeds.</p> <p>Results</p> <p>We took a multiparallel approach that combines ESTs, protein profiling and microarray analyses to look into the gene expression landscape in the endosperm of the oilseed crop <it>Brassica napus</it>. An EST collection of over 30,000 entries allowed us to detect close to 10,000 unisequences expressed in the endosperm. A protein profile analysis of more than 800 proteins corroborated several signature pathways uncovered by abundant ESTs. Using microarray analyses, we identified genes that are differentially or highly expressed across all developmental stages. These complementary analyses provided insight on several prominent metabolic pathways in the endosperm. We also discovered that a transcription factor <it>LEAFY COTYLEDON </it>(<it>LEC1</it>) was highly expressed in the endosperm and that the regulatory cascade downstream of <it>LEC1 </it>operates in the endosperm.</p> <p>Conclusion</p> <p>The endosperm EST collection and the microarray dataset provide a basic genomic resource for dissecting metabolic and developmental events important for oilseed improvement. Our findings on the featured metabolic processes and the <it>LEC1 </it>regulatory cascade offer new angles for investigation on the integration of endosperm gene expression with embryo development and storage product deposition in seed development.</p

Simultaneous quantification of nine flavonoids in Ginkgo biloba extract tablets by HPLC-DAD

A new HPLC-DAD method has been developed and validated for the simultaneous analysis of nine flavonoids (rutin, myricetin, quercitrin, quercetin, luteolin, genistein, kaempferol, apigenin, and isorhamnetin) in Ginkgo biloba tablets. The analytes were separated on a kromasil C18 column and recorded at 254 nm. The greatest resolution was achieved with methanol-0.1 % formic acid gradient at a flow rate of 1.0 mL min-1 For all the analytes, the correlation coefficients for all the calibration plots (R2<0.999) showed good linearity over the range tested. The method was validated for repeatability, precision, stability, accuracy, selectivity, and robustness. The validated method has been successfully applied to simultaneous analysis of these active components in Ginkgo biloba tablets from different manufacturers.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Structure and Evolution of Glycogen Branching Enzyme N-Termini From Bacteria

In bacteria, glycogen plays important roles in carbon and energy storage. Its structure has recently been linked with bacterial environmental durability. Among the essential genes for bacterial glycogen metabolism, the glgB-encoded branching enzyme GBE plays an essential role in forming α-1,6-glycosidic branching points, and determines the unique branching patterns in glycogen. Previously, evolutionary analysis of a small sets of GBEs based on their N-terminal domain organization revealed that two types of GBEs might exist: (1) Type 1 GBE with both N1 and N2 (also known as CBM48) domains and (2) Type 2 GBE with only the N2 domain. In this study, we initially analyzed N-terminal domains of 169 manually reviewed bacterial GBEs based on hidden Markov models. A previously unreported group of GBEs (Type 3) with around 100 amino acids ahead of the N1 domains was identified. Phylogenetic analysis found clustered patterns of GBE types in certain bacterial phyla, with the shorter, Type 2 GBEs predominantly found in Gram-positive species, while the longer Type 1 GBEs are found in Gram-negative species. Several in vitro studies have linked N1 domain with transfer of short oligosaccharide chains during glycogen formation, which could lead to small and compact glycogen structures. Compact glycogen degrades more slowly and, as a result, may serve as a durable energy reserve, contributing to the enhanced environmental persistence for bacteria. We were therefore interested in classifying GBEs based on their N-terminal domain via large-scale sequence analysis. In addition, we set to understand the evolutionary patterns of different GBEs through phylogenetic analysis at species and sequence levels. Three-dimensional modeling of GBE N-termini was also performed for structural comparisons. A further study of 9,387 GBE sequences identified 147 GBEs that might belong to a possibly novel group of Type 3 GBE, most of which fall into the phylum of Actinobacteria. We also attempted to correlate glycogen average chain length (ACL) with GBE types. However, no significant conclusions were drawn due to limited data availability. In sum, our study systematically investigated bacterial GBEs in terms of domain organizations from evolutionary point of view, which provides guidance for further experimental study of GBE N-terminal functions in glycogen structure and bacterial physiology

Multiple compounds determination and fingerprint analysis of herbal preparation Shuang-Huang-Lian capsule by HPLC-DAD

The objective of this paper was to develop a high performance liquid chromatography with diode array detection both for chromatographic fingerprint and simultaneous determination of twelve analytes of Shuang-Huang-Lian (SHL) capsule. The chromatographic separation was performed on an Aglient Zorbax SB-C18 column with a gradient elution program using a mixture of acetonitrile and 0.2 % acetic acid as mobile phase within 110 min detected at 278 nm wavelength. For fingerprint analysis, 50 peaks were selected as the common peaks to evaluate the similarities of different samples collected from different pharmaceutical companies in China, and two kinds of data, relative retention time and relative peak area were used to identify the common peaks in samples for investigation. SHL capsules from different batches of the same manufacturer or different manufacturers showed a close similarity. For quantitative analysis, linear regressions, limit of detection and quantification, intra-day and inter-day precisions, recovery, repeatability and stability were all tested and good results were obtained to simultaneously determine the 12 marker compounds in the samples. The validated method coupled with multiple compounds determination and fingerprint analysis is a powerful and meaningful tool to comprehensively conduct the quality control of TCM.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The effects of psychiatric disorders on the risk of chronic heart failure: a univariable and multivariable Mendelian randomization study

BackgroundSubstantial evidence suggests an association between psychiatric disorders and chronic heart failure. However, further investigation is needed to confirm the causal relationship between these psychiatric disorders and chronic heart failure. To address this, we evaluated the potential effects of five psychiatric disorders on chronic heart failure using two-sample Mendelian Randomization (MR).MethodsWe selected single nucleotide polymorphisms (SNPs) associated with chronic heart failure and five psychiatric disorders (Attention-Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Major Depression, Bipolar Disorder and Schizophrenia (SCZ)). Univariable (UVMR) and multivariable two-sample Mendelian Randomization (MVMR) were employed to assess causality between these conditions. Ever smoked and alcohol consumption were controlled for mediating effects in the multivariable MR. The inverse variance weighting (IVW) and Wald ratio estimator methods served as the primary analytical methods for estimating potential causal effects. MR-Egger and weighted median analyses were also conducted to validate the results. Sensitivity analyses included the funnel plot, leave-one-out, and MR-Egger intercept tests. Additionally, potential mediators were investigated through risk factor analyses.ResultsGenetically predicted heart failure was significantly associated with ADHD (odds ratio (OR), 1.12; 95% CI, 1.04–1.20; p = 0.001), ASD (OR, 1.29; 95% CI, 1.07–1.56; p = 0.008), bipolar disorder (OR, 0.89; 95% CI, 0.83–0.96; p = 0.001), major depression (OR, 1.15; 95% CI, 1.03–1.29; p = 0.015), SCZ (OR, 1.04; 95% CI, 1.00–1.07; p = 0.024). Several risk factors for heart failure are implicated in the above cause-and-effect relationship, including ever smoked and alcohol consumption.ConclusionOur study demonstrated ADHD, ASD, SCZ and major depression may have a causal relationship with an increased risk of heart failure. In contrast, bipolar disorder was associated with a reduced risk of heart failure, which could potentially be mediated by ever smoked and alcohol consumption. Therefore, prevention strategies for heart failure should also incorporate mental health considerations, and vice versa