Chemical composition analysis of Angelica sinensis (Oliv.) Diels and its four processed products by ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry combining with nontargeted metabolomics

Angelica sinensis (Oliv.) Diels. has been used for women to enrich the blood, prevent and treat blood deficiency syndrome in Traditional Chinese Medicine for thousands of years. Wine-processed Angelica sinensis, soil-processed Angelica sinensis, oil-processed Angelica sinensis, and charred-processed Angelica sinensis are the most significant four processed products used in Chinese clinic. However, there have been few studies aimed at comparing their chemical differences. Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry combining with nontargeted metabolomics was applied to investigate the diversity of processed products of Angelica sinensis. A total of 74 compounds with the variable importance in the projection value more than 1.5 and P less than 0.05 in ANOVA were highlighted as the compounds that contribute most to the discrimination of Angelica sinensis and four processed products. The results showed the metabolic changes between Angelica sinensis and its four processed products, there were 19 metabolites, 3 metabolites, 6 metabolites, and 45 metabolites were tentatively assigned in soil-processed Angelica sinensis, wine-processed Angelica sinensis, oil-processed Angelica sinensis, and charred-processed Angelica sinensis, respectively. These results suggested that the proposed metabolomics approach was useful for the quality evaluation and control of processed products of Angelica sinensis.     

A new method providing complementary explanation of the blood-enriching function and mechanism of unprocessed Angelica sinensis and its four kinds of processed products based on tissue-integrated metabolomics and confirmatory analysis

Angelica sinensis (AS) is a common Traditional Chinese Medicine used for tonifying blood in China. Unprocessed AS and its four kinds of processed products (ASs) are used to treat blood deficiency syndrome in the country. The different blood-tonifying mechanisms of ASs remain unclear. In this work, a novel method integrating metabolomics and hematological and biochemical parameters was established to provide a complementary explanation of blood supplementation mechanism of ASs. Our results revealed that different ASs exhibited various blood supplementation effect, and that AS parched with alcohol demonstrated the best blood supplementation effect. Eight metabolites from liver tissue and 12 metabolites from spleen tissue were considered to be potential biomarkers. These biomarkers were involved in four metabolic pathways. Correlation analysis results showed that l -aspartic acid and l -alanine (spleen tissue), linoleic acid, and l -cystathionine (liver tissue) exhibited a high positive or negative correlation with the aforesaid biochemical indicators. The blood-supplementation effect mechanism of ASs were related to four metabolic pathways. l -Aspartic acid and l -alanine (spleen tissue), linoleic acid, and l -cystathionine (liver tissue) were the four key metabolites associated with the blood supplementation effect of ASs. This study gives a complementary explanation of the blood supplementation effect and mechanism of action of ASs.     

Screening of polysaccharides from the differently processed products of Angelica sinensis with the best liver protection effect on chicken and the intervention mechanism study based on tandem mass tag proteomics and multiple reaction monitoring approach

The incidence of colibacillosis in poultry is on the rise, significantly affecting the chicken industry. Ceftiofur sodium (CS) is frequently employed to treat this disease, resulting in lipopolysaccharide (LPS) buildup. Processing plays a vital role in traditional Chinese veterinary medicine. The potential intervention in liver injury by polysaccharides from the differently processed products of Angelica sinensis (PDPPAS) induced by combined CS and LPS remains unclear. This study aims to investigate the protective effect of PDPPAS on chicken liver injury caused by CS combined with LPS buildup and further identify the polysaccharides with the highest hepatoprotective activity in chickens. Furthermore, the study elucidates polysaccharides’ intervention mechanism using tandem mass tag (TMT) proteomics and multiple reaction monitoring (MRM) methods. A total of 190 1-day-old layer chickens were randomly assigned into 12 groups, of which 14 chickens were in the control group and 16 in other groups, for a 10-day trial. The screening results showed that charred A. sinensis polysaccharide (CASP) had the most effective and the best hepatoprotective effect at 48 h. TMT proteomics and MRM validation results demonstrated that the intervention mechanism of the CASP high-dose (CASPH) intervention group was closely related to the protein expressions of FCER2, TBXAS1, CD34, AGXT, GCAT, COX7A2L, and CYP2AC1. Conclusively, the intervention mechanism of CASPH had multitarget, multicenter regulatory features.     

Urinary metabolomics analysis reveals the effect of volatile oil from Angelica sinensis on LPS‐induced inflammation rats

Lipopolysaccharide (LPS)‐induced inflammation occurs commonly and volatile oil from Angelica sinensis (VOAS) can be used as an anti‐inflammatory agent. The molecular mechanisms that allow the anti‐inflammatory factors to be expressed are still unknown. In this paper, we applied gas chromatography–mass spectrometry (GC–MS) and high‐performance liquid chromatography–time‐of‐flight mass spectrometry (LC‐Q/TOF–MS) based on a metabolomics platform coupled with a network approach to analyze urine samples in three groups of rats: one with LPS‐induced inflammation (MI); one with intervention with VOAS; and normal controls (NC). Our study found definite metabolic footprints of inflammation and showed that all three groups of rats, MI, intervention with VOAS and NC have distinct metabolic profiles in urine. The concentrations of 48 metabolites differed significantly among the three groups. The metabolites in urine were screened by the GC–MS and LC‐Q/TOF–MS methods. The significantly changed metabolites (p < 0.05, variable importance in projection > 1.5) between MI, NC and VOAS were included in the metabolic networks. Finally, hub metabolites were screened, including glycine, arachidonic acid, l ‐glutamate, pyruvate and succinate, which have high values of degree (k). the Results suggest that disorders of glycine, arachidonic acid, l ‐glutamate, pyruvate and succinate metabolism might play an important part in the predisposition and development of LPS‐induced inflammation. By applying metabolomics with network methods, the mechanisms of diseases are clearly elucidated.     

基于超高效液相色谱-四极杆飞行时间质谱联用技术的血瘀模型大鼠血浆代谢组学分析

采用盐酸肾上腺素加冰水浴建立急性血瘀大鼠模型，使用超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF/MS）检测空白对照组与血瘀模型组中血浆代谢物，用主成分分析（PCA）、有监督偏最小二乘法判别分析（PLS-DA）及正交偏最小二乘法判别分析（OPLS-DA）对代谢组学数据进行多维统计分析，筛选潜在生物标志物。与对照组相比，在血瘀模型组大鼠血浆中检测出46个差异代谢物，血瘀模型组中乙酰胆碱、N6，N6，N6-三甲基-L-赖氨酸、胞嘧啶、乙酰肉碱等21个代谢物显著上调，吲哚丙酸、LysoPC（14：0）等25个代谢物显著下调，可能与脂质代谢、半乳糖代谢、亚油酸代谢、不饱和脂肪酸生物合成、糖酵解、花生四烯酸代谢等通路有关。代谢产物可作为血瘀证研究中的重要标记物，该研究结果有助于揭示血瘀证的发病机制，可为临床血瘀疾病的诊断及选用药物治疗提供思路，为后续治疗手段提供参考依据。     

Effects of Tao‐Hong‐Si‐Wu decoction on acute blood stasis in rats based on a LC‐Q/TOF‐MS metabolomics and network approach

A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of Tao‐Hong‐Si‐Wu decoction (THSWD) on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice‐cold water following two injections with epinephrine. The hemorheological indicators [whole blood viscosity (WBV) and plasma viscosity (PV)] and the blood coagulation indicators [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved 10 pathways and five hub metabolites, namely, l ‐glutamate, l ‐phenylalanine, N‐acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted to close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped to evaluate the effects of THSWD on acute blood stasis.     

Metabolomics study of cured tobacco using liquid chromatography with mass spectrometry: Method development and its application in investigating the chemical differences of tobacco from three growing regions

Cured tobacco is an important plant material. Component studies are a big challenge for its significantly diverse chemical properties and vastly different concentrations. In this work, liquid chromatography with quadrupole time‐of‐flight mass spectrometry was used to perform a metabolomics study of cured tobacco owing to its efficient separation and detection of semipolar metabolites. A solvent of methanol/water (8:2, v/v) and 30 min of ultrasound time were found to be optimal to perform extraction. 95, 92, and 93% of metabolite features had within 20% of coefficient of variation for repeatability, intraday and interday precision analysis, respectively, indicating a good stability of the method developed. 113 metabolites were identified in cured tobacco based on accurate mass, retention time, and MS/MS fragments. The developed method was applied to a metabolomics study of cured tobacco from three growing regions. Forty three metabolites were found to be contributed to the classification. It is shown that the developed method can be applied to metabolomics analysis of plant materials.     

Density functional computational studies on the glucose and glycine Maillard reaction: Formation of the Amadori rearrangement products

Theoretical energy changes of various intermediates leading to the formation of the Amadori rearrangement products (ARPs) under different mechanistic assumptions have been calculated, by using open chain glucose (O‐Glu)/closed chain glucose (A‐Glu and B‐Glu) and glycine (Gly) as a model for the Maillard reaction. Density functional theory (DFT) computations have been applied on the proposed mechanisms under different pH conditions. Thus, the possibility of the formation of different compounds and electronic energy changes for different steps in the proposed mechanisms has been evaluated. B‐Glu has been found to be more efficient than A‐Glu, and A‐Glu has been found more efficient than O‐Glu in the reaction. The reaction under basic condition is the most favorable for the formation of ARPs. Other reaction pathways have been computed and discussed in this work. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

Effect of wine processing and acute blood stasis on the serum pharmacochemistry of rhubarb: A possible explanation for processing mechanism

As a specific item mentioned in traditional Chinese medicine theory, processing can fulfill different requirements of therapies. Crude and wine‐processed rhubarbs are used as drastic and mild laxatives, respectively. In this study, a practical method based on ultra‐fast liquid chromatography coupled with diode‐array detection and ion trap time‐of‐flight mass spectrometry was developed to screen and analyze multiple absorbed bioactive components and metabolites in the serum of both normal and acute blood stasis rats after oral administration of crude or wine‐processed rhubarbs. A total of 16 compounds, mainly including phase II metabolites, were tentatively identified. Possible explanations for the processing‐induced changes in pharmacological effects of traditional Chinese medicines were first explored at serum pharmacochemistry level.     

Coupling between a fluorinated olefin and a perfluorinated iodide: a model study on the reaction mechanism of perfluorinated polymer cross-linking

In a model study, , , - and - correlated NMR techniques confirm a Markovnikov type reaction intermediate for the major coupling products between a short, low MW perfluorinated iodide C₂F₅I (I) and a short, low MW fluorinated olefin CF₃(CF₂)₇CHCH₂ (II). The reaction is peroxide induced (di-t-butyl peroxide, DTBP) and is conducted at 140 °C for a 3 h reaction time in a sealed glass ampoule. Side reaction products due to the reaction of DTBP with radical reaction intermediates were also observed and identified. The study aimed to mimic as closely as possible the peroxide-initiated coupling reaction between an iodine terminated fluoropolymer (model compound I) and its fluorinated di-olefin coupling agent (model compound II). A mono-olefin was chosen to simplify the model reaction.     

Influence of pyrolysis temperature and time on the cellulose fast pyrolysis products: Analytical Py-GC/MS study

Analytical pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) was employed to achieve fast pyrolysis of cellulose and on-line analysis of the pyrolysis vapors. Experiments were performed to reveal the effects of pyrolysis temperature and time on the distribution of the pyrolytic products, especially the formation characteristics of eighteen important products. During the fast pyrolysis process, the cellulose started decomposition to form organic volatile products at the set pyrolysis temperature of 400 °C. The pyrolytic products included various anhydrosugars (dominated by the levoglucosan (LG)), anhydrosugar derivatives (mainly the levoglucosenone (LGO), 1,4:3,6-dianhydro-α-d-glucopyranose (DGP), 1,5-anhydro-4-deoxy-d-glycero-hex-1-en-3-ulose (APP) and 1-hydroxy-3,6-dioxabicyclo[3.2.1]octan-2-one (LAC)), furan compounds (typically the 5-hydroxymethyl-furfural (HMF), furfural (FF) and furan (F)), as well as light linear carbonyls (mainly the hydroxyacetaldehyde (HAA) and 1-hydroxy-2-propanone (HA)). These products were generated with different characteristics. The LG was the most important product, it was thermally stable, and its formation was favored at elevated pyrolysis temperature and time. Most of the other products were also enhanced at elevated pyrolytic conditions. However, some products, such as the LGO, were favorable to be produced at low temperatures. Based on these characteristics, discussion was performed on the possible pyrolytic pathways for the formation of the important products.     

Microbial‐induced synthesis of mineralization products based on the capture of carbon dioxide: Characteristics,reaction kinetics,interfacial adhesion properties,and mechanism of action

As a new type of green environment‐friendly cementitious material, microbial‐induced mineralization products have garnered more and more attention. In this paper, the synthesis of mineralization products under microbial inducement was conducted. The composition and microstructure of mineralization products were studied using energy‐dispersive spectrometer (EDS), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscope (TEM). The results showed that mineralization products were calcite, while the shape was similar to globular type, and particle size was about 5 μm. The effect of microbial culture solution, secretion solution, and concentration on the conductivity of the solution was compared and analyzed. During the formation of mineralization products, bacterial bodies not only played the role of nucleation sites but also accelerated the deposition of mineralization products. Thus, it could be seen that the bacterial bodies had a certain influence on the reaction kinetics. The adhesion force of mineralization products was evaluated by the interfacial adhesion properties between the mineralization products and glass slides. The results of the sonication test and scratch test indicated that the interfacial adhesion strength between mineralization products and glass slides was closely related to the mass of mineralization products deposited. The larger the mass of mineralization products deposited, the greater the interfacial adhesion strength. Based on the above research and analysis, the reaction process and mechanism model of microbial‐induced mineralization were defined.     

Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N'-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine: water-assisted mechanism and cluster-continuum model

The hydrolysis reaction of N,N-dimethyl-N'-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine (DMPFA), a model compound of the antivirus drug amidine-3TC (3TC = 2', 3'-dideoxy-3'-thiacytidine), is investigated by the hybrid density functional theory B3LYP/6-31+G (d,p) method. The hydrolysis reaction of the title compound is predicted to undergo via two pathways, each of which is a stepwise process. Path A is the addition of H2O to the C=N double bond in the amidine group to form a tetrahedral structure in its first step, and then the transfer of the H atom of hydroxyl leads to the corresponding products via four possible channels. Path B simultaneously involves the nucleophilic attack of H2O to the C atom of the C=N bond and the proton transfer to the N atom of amino group leading to the cleavage of the C-N single bond in the amidine group. The results indicate that path A is more favorable than path B in the gas phase. Moreover, to simulate the title reaction in aqueous solution, water-assisted mechanism and the cluster-continuum model, based on the SCRF/CPCM model, are taken into account in our work. The results indicate that it is rational for two water molecules served as a bridge to assist in the first step of path A and that cytosine rather than the cytosine-substituted formamide should be released from the tetrahedral intermediate via s six-membered cycle transition state (channel 2). Our calculations exhibit that the process toward the tetrahedral intermediate is the rate-determining step both in the gas phase and in aqueous solution.     

The latest research progress on the prevention of storage pests by natural products: Species,mechanisms, and sources of inspiration

The quality of grains is influenced by storage pests, which are not only spoilers of stored grain, but also vectors of human and animal diseases. Chemical pesticides play an essential role in the cultivation and storage of cereals, however, due to the low degradability and residual toxicity of synthetic pesticides on the environment and non-target organisms, as well as the increasing resistance of target organisms to them, consideration should be given to the development of alternative pest control agents. Compounds isolated from natural sources have emerged as preferred targets for the development of novel insecticidal agents because of their eco-friendliness, safety, and effectiveness. In this review, we primarily focus on the natural product (NPs) control of storage pests. The effective monomer components of NPs and their anti-insect mechanisms were discussed, and natural sources of inspiration and models for insect repellents are described. This review aimed to provide guidelines for the exploitation and utilization of green and efficient natural insecticides.