Study on the differences in chemical composition of Scutellaria baicalensis leaves from different origins in Shanxi Province based on plant metabolomics and targeted quantitative analysis / 药学学报

By integrating plant metabonomics and target quantitative analysis methods, this study systematically analyzed the differences of chemical constituents in Scutellaria baicalensis leaves from different producing areas in Shanxi, so as to provide theoretical basis for rational and effective utilization of Scutellaria baicalensis leaves. Based on the idea of plant metabonomics, the liquid quality of 53 batches of Scutellaria baicalensis leaves from 8 different producing areas in Shanxi was analyzed by UPLC-QTOF-MS, and the collected data were imported into SIMCA 14.1 software for multivariate statistical analysis to screen the different chemical constituents among different habitats in Shanxi. Meanwhile, a method for simultaneous determination of 7 flavonoids and 3 organic acids in Scutellaria baicalensis leaves was optimized and established to quantitatively analyze the differences of chemical components in Scutellaria baicalensis leaves from different producing areas in Shanxi. The results of plant metabonomics showed that there were differences in the chemical composition of Scutellaria baicalensis leaves in northern Shanxi (Datong, Xinzhou), Jinzhong (Yangquan, Luliang) and southern Shanxi (Changzhi, Yuncheng, Jincheng, Linfen): there were 14 significant differences in chemical composition between northern Shanxi and Jinzhong; there were 18 significant differences in chemical constituents between southern Shanxi and central Shanxi. There were 15 significant differences in chemical constituents between northern Shanxi and southern Shanxi. Among them, scutellarin and isocarthamidin-7-O-glucuronide were the common differences among the three regions, and the content of scutellarin was the highest in southern Shanxi and the lowest in northern Shanxi. The content of isocarthamidin-7-O-glucuronide was the highest in Jinzhong area and the lowest in northern Shanxi area. Quantitative analysis further confirmed that the average contents of apigenin, naringenin and citric acid were the highest in northern Shanxi, scutellarin, caffeic acid, apigenin-7-O-glucuronide, malic acid and wogonoside were the highest in southern Shanxi, and wogonoside and baicalin were the highest in central Shanxi. This study is of great significance to the quality control of Scutellaria baicalensis leaf resources, and provides theoretical basis for rational and effective utilization of Scutellaria baicalensis leaf resources.

Innovation and application of metabolomics technology for research in the biomedical field / 药学学报

Metabolomics technology played an important role in the field of biomedical research, such as disease diagnosis, pathogenesis analysis, drug target exploration, formulation of treatment guidelines, etc. Due to the systematic and holistic characteristics of metabolomics research, it has shown certain advantages in the analysis of the basis of pharmacodynamic substances of traditional Chinese medicines and the development of new medicines from traditional Chinese medicines. With the continuous innovation of metabolomics research, many advanced technologies have been developed, which make up for the shortcomings of conventional metabolomics studies in searching for disease targets, identifying functional compounds and interpreting biological significance. Furthermore, the rapid development of metabolomics technology has created new opportunities for the diagnosis of diseases and the development of new drugs in traditional Chinese medicine. Herein, different from conventional metabolomics techniques and methods, nine new metabolomics technologies with wide application prospects in the past 10 years were reviewed from the perspective of new tools, new ideas and new samples, with a view to providing new insights on relevant metabolomics research in the biomedical field and providing new motivation for innovation and development of metabolomics technologies.

Based on plasma metabonomics and network analysis to research the mechanisms of Chaigui granules for treating depression / 药学学报

The purpose of this study was to systematically analyze the antidepressant mechanism of Chaigui granules from the perspective of biological metabolic network by using integrated metabolomics and biological network analysis tools. The model of chronic unpredictable mild stress (CUMS) depression rat was established, and LC-MS-based plasma metabolomics was used to identify the key metabolites and analyze metabolic pathways underlying the antidepressant effects of Chaigui Granules. The key metabolites regulated by Chaigui granules was integrated with biological network analysis tools to further focus on the key metabolic pathways and explore the potential targets of the antidepressant effect of Chaigui granules. The results showed that there were significant differences in the plasma levels of 20 metabolites in the model group compared with the control group (P < 0.05), Chaigui granules significantly regulated 12 metabolites including docosatrienoic acid, 3-hydroxybutyric acid, 4-hydroxybenzaldehyde, chenodeoxycholic acid, cholic acid, L-glutamine, glycocholic acid, linoleyl carnitine, L-tyrosine, N-acetylvaline, palmitoylcarnitine, arachidonic acid. Further network analysis of the key metabolites regulated by Chaigui granules indicated that plasma arachidonic acid metabolism might be the core pathway for the antidepressant effect of Chaigui granules, with 10 proteins were potential targets for the antidepressant effect of Chaigui granules, including CYP2B6, CYP2E1, CYP2C9, CYP2C8, PLA2G6, PTGS2, ALOX15B, PTGS1, ALOX12 and ALOX5. The animal experimental operations involved in this paper was followed the regulations of the Animal Ethics Committee of Shanxi University and passed the animal experimental ethical review (Approval No. SXULL2020028).

Advances in the pathogenesis of depression based on purinergic system and purine metabolism / 药学学报

Depression was a complex and difficult to regulate disease, which was closely related to purinergic system and purine metabolism disorder. Although there had been studies to improve depression by regulating purinergic system, the mechanism of action was complex and needed to be sorted out. Recently, a large number of studies had found that the addition of exogenous purine metabolites adenosine, inosine and guanosine had a significant antidepressant effect, indicating that regulating the level of purine substances in purine metabolism could also improve depression, which was of great significance to the further study of the pathogenesis and treatment of depression. In view of this, this study reviewed the relationship between purinergic system or purine metabolism and depression, in order to provide a reference for the further study of the pathogenesis of depression.

Metabolic module identification and biological mechanism of Xiaoyaosan for treatment of depression / 药学学报

The antidepressant effect of Xiaoyaosan has been demonstrated. It is of value to explore the biological mechanism of Xiaoyaosan in the treatment of depression from the perspective of functional modules by using the method of functional module division of the metabolic network. The differential metabolites and related enzymes and proteins regulated by Xiaoyaosan were identified in the database. Pathway enrichment analysis and crosstalk pathway analysis of Xiaoyaosan regulated metabolites was carried out. A network of differentially regulated metabolites and their enzymes and proteins was constructed by using the STRING tool. The CNM decomposition algorithm was used to extract the functional modules of the network and enrichment analysis of functional modules was carried out. The results show that Xiaoyaosan regulates 97 differential metabolites, 234 related enzymes and 258 depression-related proteins. The pathways crosstalk analysis was divided into two sub-networks, one of which is related to the neural system and cell signal transduction, the other is related to the endocrine system and metabolic pathways. KEGG pathway enrichment analysis of the network and 9 functional modules extracted by the CNM algorithm shows that module 1 and module 3 belong to the pathways that can be enriched into more pathways with fewer proteins. The corresponding functions of these pathways include the endocrine system, amino acid metabolism, the nervous system and signal transduction. In this study, pathway crosstalk analysis and metabolic network module division strategies were used to explain the biological mechanism of Xiaoyaosan in the treatment of depression, providing ideas and methods for in-depth study of the pharmacological mechanism of this traditional Chinese medicine from the perspective of metabolic regulation.

The anti-aging effects of different parts of Scutellaria baicalensis Georgi based on 1H NMR urine metabolomics / 药学学报

The effects of alcohol extracts from roots, stems, leaves, and flowers of Scutellaria Baicalensis Georgi (SBG) on endogenous metabolism in D-gal-induced aging-model rats were investigated by 1H NMR metabolomics. Results showed that 32 endogenous metabolites were identified in the urine. Combined with the VIP value and t-test, 14 different metabolites were found by multivariate statistical analysis of the spectrum. Compared with the control group, the content of α-ketoglutaric acid, hippuric acid and 3-hydroxybutyrate in the urine of rats in the model group was significantly decreased (P<0.05) and the content of trimethylamine oxide, glycine, alanine, lactic acid, dimethylglycine, acetate, pyruvate, taurine, allantoin, betaine, N-acetylated glycoprotein was significantly increased (P<0.05). The metabolites were mainly derived from taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; pyruvate metabolism; glycolysis/gluconeogenesis; glyoxylic acid and dicarboxylic acid metabolism; and the tricarboxylic acid cycle. The content of differential metabolites in urine samples was altered by the alcohol extracts from the different parts of SBG. Leaves extracts of SBG had the greatest effect on urine metabolites, and mainly affected taurine and hypo-taurine metabolism; glycine, serine and threonine metabolism; and pyruvate metabolism. This study provides a reliable experimental basis for the future development of SBG. This animal experiment was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036).

Anti-aging effect of Scutellaria baicalensis Georgi leaves based on 1H NMR serum and liver metabolomics / 药学学报

@#In this study a <italic>D</italic>-galactose-induced aging rat model combined with ¹H NMR of serum and liver metabolomics were used to explore the anti-aging effect and the potential metabolic regulatory mechanism of <italic>Scutellaria baicalensis</italic> Georgi leaves. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of Shanxi University. The results of physical characteristics, an open field test and serum biochemical indexes indicated that <italic>Scutellaria baicalensis</italic> Georgi leaves had an anti-aging effect that could ameliorate the characteristics of aging rats such as acquired hair loss and slow response, improve the spontaneous activity of aging rats, and decrease lipid peroxidation and glycosylation damage induced by <italic>D</italic>-galactose. Serum and liver metabolomics further revealed that <italic>Scutellaria baicalensis</italic> Georgi leaves could decrease serum and liver metabolism disturbances in aging rats, mainly through different metabolites and metabolic pathways. Specifically, 12 differential metabolites including glutamine and glutamate, 11 metabolic pathways including <italic>D</italic>-glutamine and <italic>D</italic>-glutamate metabolism and alanine, aspartate and glutamate metabolism in serum were significantly altered after the treatment. Simultaneously, five differential metabolites such as <italic>α</italic>-glucose and <italic>β</italic>-glucose, two metabolic pathways that are glycolysis or gluconeogenesis, and starch and sucrose metabolism in the liver were markedly altered.

The mechanism of the anti-depression effect of the Radix Bupleuri-Radix Paeoniae Alba herb pair determined by liver metabolomics / 药学学报

This study analyzed the effect of the Radix Bupleuri-Radix Paeoniae Alba herb pair on endogenous metabolites in rats with chronic unpredictable mild stress (CUMS)-induced depression by using LC-MS liver metabolomics. Rats were randomly divided into 5 groups: a normal control group, a CUMS model group, a venlafaxine-positive group, and a high-low dose group for the Radix Bupleuri-Radix Paeoniae Alba herb pair, with continuous modeling and administration over 28 days. The efficacy of Radix Bupleuri-Radix Paeoniae Alba herb pair was evaluated by measuring traditional pharmacodynamic indicators of depression (body weight, open field test, sucrose preference test and forced swimming test). Animal experimentation was approved by the Committee on the Ethics of Animal Experiments of Shanxi University (SXULL2016036). Liver metabolic profiles were obtained by the UHPLC-Q Exactive Orbitrap-MS metabolomics technique. The results show that the Radix Bupleuri-Radix Paeoniae Alba herb pair can significantly decrease depression-like behavior of rats in the CUMS model group. Increases in 25 depression-related metabolites were identified by LC-MS metabonomics, and the Radix Bupleuri-Radix Paeoniae Alba herb pair could significantly decrease 16 of them. Metabolic pathway analysis showed that D-glutamine and D-glutamate metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and glutathione metabolism were the main metabolic pathways altered by this herb pair in CUMS model rats.

Research progress of traditional Chinese antidepressant herb-pair / 药学学报

@#Depression, a global disease with various pathogenic factors, is seriously affecting human physical and mental health. In Chinese traditional medical theory, the disease belongs to the category of "Yu Zheng". At present, on the one hand, adverse reactions to antidepressant western medicine are becoming more and more prominent. On the other hand, the study of their antidepressant active ingredients and compatibility mechanisms has become a difficult field in the traditional Chinese medicine compounds due to their complexity. The Chinese antidepressant herb-pairs has become a hot topic in the field of antidepressant research. Herb-pair is the core of traditional Chinese medicine compound. In addition, the compound itself is a herb-pair. The study of traditional Chinese antidepressant herb-pairs is more conducive to clarify the compatibility mechanism of herb interaction and the mechanism of antidepressants on the body.Therefore, this paper systematically expounds antidepressant herb-pairs from the study of material, pharmacokinetics and efficacy, which aims at providing theoretical support for the compatibility mechanism of antidepressant herb-pairs and the research of new antidepressant drugs.

Research progress about the anti-aging effect and mechanism of flavonoids from traditional Chinese medicine / 药学学报

Aging is a normal physiological process involving coaction of many factors. The anti-aging effects of natural products have been studied by many domestic and international scholars, but not far enough, which still needed to be explored. Flavonoids, as natural products, have a variety of pharmacological activities and present in many traditional Chinese medicines. In recent years, research results indicate that flavonoids can delay the aging process of the nervous, immune, and reproductive systems, and the liver, skin and other tissues. The anti-aging effects of flavonoids have attracted more and more attention. Therefore, development of anti-aging drugs from flavonoids is of great significance to improve the quality of life for the elderly and slow the process of aging. However, the mechanism of the anti-aging effect of flavonoids remains unknown at present. This review will discuss the anti-aging effect and mechanisms of flavonoids in traditional Chinese medicine from the aspects of cellular signaling pathways and metabolic pathways based on the modern theories of aging.

Involvement of mitochondrial apoptotic pathway and MAPKs/NF-κ B inflammatory pathway in the neuroprotective effect of atractylenolide III in corticosterone-induced PC12 cells / 中国天然药物

Atractylenolide III (ATL-III), a sesquiterpene compound isolated from Rhizoma Atractylodis Macrocephalae, has revealed a number of pharmacological properties including anti-inflammatory, anti-cancer activity, and neuroprotective effect. This study aimed to evaluate the cytoprotective efficiency and potential mechanisms of ATL-III on corticosterone injured rat phaeochromocytoma (PC12) cells. Our results demonstrate that ATL-III increases cell viability and reduces the release of lactate dehydrogenase (LDH). The results suggest that ATL-III protects PC12 cells from corticosterone-induced injury by inhibiting the intracellular Ca overloading, inhibiting the mitochondrial apoptotic pathway and modulating the MAPK/NF-ΚB inflammatory pathways. These findings provide a novel insight into the molecular mechanism by which ATL-III protected the PC12 cells against corticosterone-induced injury for the first time. Our results provide the evidence that ATL-III may serve as a therapeutic agent in the treatment of depression.

Study on aging animal models and its application in activity screening of anti-aging drugs / 中草药

Aging and aging-related diseases make human life burden increase year by year. We can solve this problem by delaying aging and reducing the incidence of aging-related diseases. Animal model is an important tool for aging research, in this paper, we focused on all kinds of models for aging study including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, senescence accelerated mouse, D-galactose induced aging model, and rhesus. The characteristics, application status, and research progress of these models were introduced separately, which provides the basis for the selection of animal models in aging research.

Comparative study on quality of Scutellaria baicalensis Georgi in different harvest periods using UHPLC-MS/MS metabolomics technology / 药学学报

The quality of Scutellaria baicalensis Georgi has a close relationship to the harvest time. With the annual and biennial Scutellaria baicalensis Georgi in different harvest periods as samples, we detected the dynamic changes of chemical compositions in their contents by UHPLC-MS/MS metabolomics technology, then identified the biomarkers of different harvest periods and analyzed their changes in content, finally analyzed the correlation among different metabolites. The results showed that chemical compositions of different harvest periods were obviously different, and showed regular changes. According to the results, if the flavonoid aglycones are chosen as the target components, the proposed harvest time could be May. If flavonoid glycosides, the time is from July to August. Plant metabolomics methodology based on UHPLC-MS/MS can be used to detect the chemical compositions of Scutellaria baicalensis Georgi in different harvest periods, which provide a reference to the optimum harvest period of Scutellaria baicalensis Georgi, and also provide a new method of quality evaluation of traditional Chinese medicinal materials.

Research advances in brain monoamine neurotransmitters in the aging-associated memory decline / 药学学报

Learning and memory decline is an important manifestation of aging, seriously affecting the health and life quality of the elderly. Aging-related learning and memory decline is often accompanied by decreased levels of norepinephrine, dopamine and serotonin neurotransmitters in the relevant brain regions. Monoamine neurotransmitters in different brain regions bind to receptors and regulate synaptic plasticity, which play an important role in learning and memory. This article reviews the changes of monoamine neurotransmitters in different brain regions, the mechanisms in regulation of learning and memory, and the factors causing abnormal levels of neurotransmitters in the process of aging in order to better understand the mechanisms of senile learning and memory decline to facilitate drug research.

Network pharmacology-based study of anti-hepatoma effects and mechanisms of matrine / 药学学报

Although multiple studies have shown that matrine can inhibit the proliferation of hepatoma cells, its mechanism of action has not been systematically investigated. In this study, the effects of matrine on the proliferation and migration of human hepatoma SMMC-7721 cells were investigated. Based on this result, anti-hepatoma target-functionally related protein interaction network of matrine was constructed, and topological analysis and clustering analysis were performed to predict the crucial targets of matrine for the anti-hepatoma effects. Pathway enrichment analysis was performed on the validated targets to predict the crucial pathways of matrine. Parts of the crucial proteins were examined by Western blot. Cellular experiments showed that matrine at concentrations of 1, 2 and 4 mg·mL-1 significantly inhibited the proliferation of SMMC-7721 cells, and matrine at concentrations of 0.5, 1 and 2 mg·mL-1 significantly inhibited the migration of SMMC-7721 cells. The results of network pharmacology suggest that matrine exerts its anti-hepatoma effects through acting on the key validated targets of heparanase (HPSE), caspase 3 (CASP3), Myc proto-oncogene protein (MYC), matrix metalloproteinases 2 (MMP2) and predicted targets of carbonic anhydrase 1 (CA1), lithostathine 1 alpha precursor (REG1A), carboxylesterases 1 (CES1) and acetaldehyde dehydrogenase 2 (ALDH2), and invasion and migration associated pathways. Western blot results suggest that matrine can down-regulate the expression of MMP2 and up-regulate the expression of CASP3. In this paper, we applied network pharmacology to explain the targets and pathways of matrine against hepatoma. The results provide a scientific basis for elucidation of the mechanisms of matrine against hepatoma.

Advances in the study of the rat model of aging induced by D-galactose / 药学学报

D-galactose (D-gal)-induced aging model is widely used in the study of the pharmacodynamics of antiaging drugs. The model has a shorter life-span, disorders in learning and memory, reduced immune function and other aging characteristics. Regular and quantitative injection of D-gal solution to rats can produce symptoms of natural aging models that are used in screening of antiaging drugs, and their pharmacological activities. This paper provides a summary of the mechanism of rat model induced with D-gal solution. The methods of building and evaluation of the aging models are provided. The theoretical basis is included to facilitate the subsequent research and experiment in the mechanism study of aging and antiaging medicines.

Quantitative analysis of eight polyacetylenes derived from Bupleuri Radix by ultra-performance liquid chromatography coupled with photodiode array detector / 中国中药杂志

To establish quantitative methods for determination of polyacetylenes in Bupleuri Radix, an ultra-performance liquid chromatography method coupled with photodiode array detector (UPLC-PDA) was developed. The analysis was performed on a Waters BEH C₁₈ column (2.1 mm×100 mm, 1.7 μm) using a gradient system of methanol and water. The flow rate was 0.3 mL•min⁻¹ and the detection wavelength was 315 nm. Eight polyacetylenes were prepared using traditional extraction and isolation method, of which compounds 7 and 8 were two new polyacetylenes. All calibration curves showed good linearity (r>0.999 0) within the concentration range. Both the intra- and inter-day precisions for eight analytes were less than 1.9%, respectively, with the mean recovery at the range of 93.21%-108.4%. Meanwhile, 17 bupleurum samples were examined with this process. The results showed a variety either the chemotaxonomic or content of polyacetylenes. The method indicated good linearity, limit of detection and quantification, precision, accuracy and recovery. The developed method allows quantitative assessment and quality control of polyacetylenes, and might be a good alternative according to detection levels in polyacetylenes from Bupleurum Radix.

Baicalein prolongs the lifespan of Drosophila melanogaster through antioxidation activity / 药学学报

In order to explore the anti-aging effect of baicalein, female Drosophila melanogaster as a model organism was used to study the effects of baicalein on natural aging model and aging models induced by hydrogen peroxide (H2O2) and paraquat. The bioinformatics approach was used to predict the possible target for the anti-aging activity of baicalein, and the target pathways were identified. The oxidative stress pathway was a focus in experiment. Baicalein at concentrations of 0.04 mg·mL-1 and 0.2 mg·mL-1 extended the mean and maximum lifespans in the natural aging model, and effectively reduced the damages of oxidative stress by H2O2 and paraquat. 31 senescence-related targets together with the oxidative stress pathway were modulated by baicalein. The experiments revealed that baicalein might delay aging process through attenuation of the oxidative stress response by decreasing the reactive oxygen species (ROS), malondialdehyde (MDA) and oxidized glutathione (GSSG) in Drosophila melanogaster.

Urinary metabolomics study of the effects of Scutellaria baicalensis Georgi ethanol extract on D-galactose-induced rats / 药学学报

The purpose of this study is to evaluate the anti-aging effects and reveal the underlying mechanism of Scutellaria baicalensis Georgi ethanol extract (SBG) in D-galactose-induced rats. Fifty rats were randomly divided into five groups: vehicle control group, D-galactose group, and D-galactose combined with 50, 100, 200 mg·kg-1 SBG. A rat aging model was induced by injecting subcutaneously D-galactose (100 mg·kg-1) for ten weeks. At the tenth week, the locomotor activity (in open-field test) and the learning and memory abilities (in Morris water maze test) were examined respectively. The urine was collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. The SBG at doses of 50, 100 and 200 mg·kg-1 treatments groups could significantly ameliorate aging process in rats' cognitive performance. The 50, 100, 200 mg·kg-1 SBG regulated citrate, pyruvate, lactate, trimethylamine (TMA), pantothenate, β-hydroxybutyrate in urine favorably toward the control group. These biochemical changes are related to the disturbance in energy metabolism, glycometabolism and microbiome metabolism, which is helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG.

Urinary metabolomics study of the effects of Scutellaria baicalensis Georgi ethanol extract on D-galactose-induced rats / 药学学报

The purpose of this study is to evaluate the anti-aging effects and reveal the underlying mechanism of Scutellaria baicalensis Georgi ethanol extract (SBG) in D-galactose-induced rats. Fifty rats were randomly divided into five groups: vehicle control group, D-galactose group, and D-galactose combined with 50, 100, 200 mg x kg(-1) SBG. A rat aging model was induced by injecting subcutaneously D-galactose (100 mg x kg(-1)) for ten weeks. At the tenth week, the locomotor activity (in open-field test) and the learning and memory abilities (in Morris water maze test) were examined respectively. The urine was collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. The SBG at doses of 50, 100 and 200 mg x kg(-1) treatments groups could significantly ameliorate aging process in rats' cognitive performance. The 50, 100, 200 mg x kg(-1) SBG regulated citrate, pyruvate, lactate, trimethylamine (TMA), pantothenate, β-hydroxybutyrate in urine favorably toward the control group. These biochemical changes are related to the disturbance in energy metabolism, glycometabolism and microbiome metabolism, which is helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG.