Spatial distribution characteristics of metabolities in rhizome of Paris polyphylla var. yunnanensis: based on MALDI-MSI / 中国中药杂志

In this study, a method was established for in-situ visualization of metabolite distribution in the rhizome of Paris polyphylla var. yunnanensis. To be specific, through matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI), the spatial locations of steroidal saponins, amino acids, organic acids, phytosterols, phytoecdysones, nucleosides, and esters in rhizome of the medicinal plant were directly analyzed, and six unknown compounds with differential distribution in rhizome tissues were identified. The specific procedure is as follows: preparation of rhizome tissue section, matrix screening and optimization, and MALDI-MSI analysis. The results showed that the steroidal saponins were mainly distributed in the central, amino acids in epidermis and cortex, low-molecular-weight organic acids in central epidermis, phytosterols in the epidermis and lateral cortex, the phytoecdysones in epidermis and cortex, nucleosides(uneven distribution) in epidermis and cortex, growth hormones around the epidermis and cortex, particularly outside the cortex, and esters in cortex with unobvious difference among different tissues. In this study, the spatial distribution of meta-bolites in the rhizome of P. polyphylla var. yunnanensis was characterized for the first time. The result can serve as a reference for identifying and extracting endogenous metabolites of P. polyphylla var. yunnanensis, exploring the synthesis and metabolism mechanisms of the metabolites, and evaluating the quality of medicinal materials.

Application of Matrix-assisted Laser Desorption Ionization Mass Spectrometry in Analysis of Traditional Chinese Medicine：A Comprehensive Review / 中国实验方剂学杂志

Traditional Chinese medicine （TCM）， which owns abundant chemical components and complex action pathways， has been widely recognized in the prevention and treatment of diseases. Some analysis methods have been emerged in order to ensure the quality of TCM and to develop new TCM drugs. Matrix-assisted laser desorption ionization mass spectrometry （MALDI-MS） is a soft ionization mass spectrometric technique with the advantages of high throughput， high sensitivity， low cost and so on. It provides technical support for the molecular level study on TCM. At present， this technique has been used in the field of composition analysis and metabonomics research of TCM， and plays an important role in the identification of Chinese herbal medicines， real-time molecular screening and the construction of metabolic network pathway of active ingredients. Among them， the selection of appropriate matrix and sample preparation technology is the key to ensure the detection effect of MALDI-MS. With the development and optimization of new matrix， the continuous improvement of sample preparation technology and the combination of MALDI-MS with various analytical methods will greatly improve the detection effect. Based on this， this paper discusses the application of MALDI-MS in TCM， including high-throughput detection of active ingredients in TCM， monitoring of the original medicines and their metabolites in vivo， and in situ visualization and characterization of tissue distribution information of active ingredients in TCM. It also discusses the application prospect and existing problems of MALDI-MS in TCM， so as to provide technical support for the identification of active ingredients in TCM， drug utilization and metabolism.

Prediction of Q-markers of Citri Reticulatae Pericarpium volatile oil and GC-MS based quantitative analysis / 中国中药杂志

This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 μL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 μL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.

Data Mining of Caryophylli Fols-containing Formula and Analysis of Its Mechanism in Treatment of Diarrhea / 中国实验方剂学杂志

Objective:Based on database mining， the high-frequency compatibility of Caryophylli Fols as the core in formulas for treating diarrhea was analyzed， and the network pharmacology was used to elucidate the mechanism of the core drug group containing Caryophylli Fols in the treatment of diarrhea. Method:The online database of traditional Chinese medicine （TCM） was intelligently crawled by Python 3.8.1 programming， and the compatibility rules of Caryophylli Fols were analyzed， and the TCM with support≥0.30， confidence≥0.90 and lift≥1.00 was set as the core drug group of Caryophylli Fols. The components were searched and screened by TCM Systems Pharmacology Database and Analysis Platform （TCMSP）， and the disease targets were collected in Therapeutic Target Datebase （TTD）， GeneCards and DisGeNET database with "Diarrhea" as the key word. The network diagram of "TCM-ingredients-potential targets" was constructed by Cytoscape 3.7.1 software， and the network of protein-protein interaction （PPI） was constructed by STRING 11.0. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis of potential targets was analyzed by R language， and the components of the core drug group were preliminarily verified and evaluated by Discovery Studio Client 2016 software. Result:A total of 155 formulas containing Caryophylli Fols for treating diarrhea were screened， involving 54 TCMs. The analysis of association rules showed that Caryophylli Fols was strongly associated with Myristicae Semen， Glycyrrhizae Radix et Rhizoma， Aucklandiae Radix and Atractylodis Macrocephalae Rhizoma in the treatment of diarrhea. The core drug group composed of these five TCMs involved 119 kinds of TCM ingredients and 114 potential targets， of which 104 potential targets were distributed in the nervous system， and the key targets were tumor protein p53 （TP53）， transcription factor activator protein-1 （JUN）， mitogen-activated protein kinase 8 （MAPK8）， interleukin-6 （IL-6）， 90 kDa heat shock protein <italic>α</italic>A1 （HSP90AA1） and so on. GO enrichment analysis mainly involved biological processes such as the regulation of neurotransmitter levels， blood circulation， hormone-mediated signal pathway and regulation of chemical synaptic transmission. IL-17 signal pathway， helper T cell 17 （Th17） cell differentiation， epidermal growth factor receptor and salmonella infection in KEGG pathways were closely related to the treatment of diarrhea. Molecular docking showed that the key target protein had high affinity with quercetin， kaempferol and <italic>β</italic>-sitosterol. Conclusion:The multi-components， multi-targets and multi-pathways involved in the core drug group of Caryophylli Fols are closely related to inflammation and nervous system， so it is speculated that it may treat diarrhea by repairing intestinal shielding integrity and regulating the levels of neurotransmitters.

Research progress on antibacterial activity of herbal volatile oil / 中国中药杂志

Due to worldwide abuse of chemical antibiotics and continuous emergence of "superbugs", the harm of bacterial drug resistance to human beings has become more and more serious. Therefore, it is of great significance to look for green antibiotics with a wide range of sources, broad antibacterial spectrum, non-toxicity or low toxicity, environmentally friendliness, diverse active components and low drug resistance. The volatile oil of traditional Chinese medicine is a kind of volatile oily liquid that exists in plants and can be distilled with steam and immiscible with water. Because of its good potential to resist drug-resistant pathogens, it is widely used in food, medicine and other fields. This paper summarized the antibacterial advantages and characteristics of volatile oil of traditional Chinese medicine, and the antibacterial effect and antibacterial mechanism of combined application of volatile oil of traditional Chinese medicine, in order to provide some theoretical basis and study ideas for solving the problem of bacterial drug resistance and developing natural and green antibiotics.

Network pharmacology research on high frequency use of Pericarpium Citri Reticulatae and Aucklandiae Radix herb pair in treatment of constipation with aromatic traditional Chinese medicine based on data mining / 中国中药杂志

Based on data mining and through the method of network pharmacology, we analyzed the mechanism of high-frequency use of herb pair in the treatment of constipation with aromatic traditional Chinese medicine in this study. Through data mining, aromatic traditional Chinese medicine was obtained for the treatment of constipation and Pericarpium Citri Reticulatae and Aucklandiae Radix herb pair was used as the research object. The volatile oil from Pericarpium Citri Reticulatae and Aucklandiae Radix was extracted by steam distillation, and the chemical compositions of the volatile oil were detected by gas chromatography-mass spectrometry(GC-MS). The targets of volatile oil from Pericarpium Citri Reticulatae and Aucklandiae Radix were searched by PubChem, TCMSP, STITCH and Swiss Target Prediction databases. The targets of constipation were predicted and screened in OMIM, Genecards-Search Resuits and TTD databases. The obtained targets were introduced into Cytoscape 3.7.1 to construct protein-protein interaction(PPI) network diagram for GO and KEGG pathway enrichment analysis by using R language. The network diagram of "component-target-pathway" was constructed according to the results of KEGG enrichment. Discovery Studio 2.5 software was used to verify the molecular docking between the components and the targets. Among them, the most frequently used pair of aromatic traditional Chinese medicine in the treatment of constipation was Pericarpium Citri Reticulatae and Aucklandiae Radix. A total of 33 compounds were detected by GC-MS, and a total of 180 common action targets of Pericarpium Citri Reticulatae and Aucklandiae Radix on volatile oil in the treatment of constipation were predicted. The key targets included CYP19 A1, PPARA, PGR, ACHE, SLC6 A2 and so on. GO enrichment analysis showed that the activities of Pericarpium Citri Reticulatae and Aucklandiae Radix on volatile oil were mainly involved in the biological processes such as circulatory system, blood circulation, and steroid hormone binding. In KEGG enrichment pathway, neuroactive ligand-receptor interaction, endocrine resistance, Ca~(2+) signal pathway and IL-17 signaling pathway showed significant effect on constipation. The results of molecular docking showed that PGR, the target protein related to the treatment of constipation, had a good binding with gamma-linolenic acid, dihydro-alpha-ionone, alpha-eudesmol, caryophyllene oxide and beta-ionone. The results show that by using data mining technology and network pharmacology, it is revealed that the active components of Pericarpium Citri Reticulatae and Aucklandiae volatile oil in high frequency use of aromatic traditional Chinese medicine can be used totreat constipation mainly through CYP19 A1, PPARA, PGR, ACHE, SLC6 A2 and other targets, providing a new idea and method for the further study of aromatic traditional Chinese medicine in the treatment of constipation.

Construction of core collection of Psammosilene tunicoides based on polymorphism of β-AS gene / 中国中药杂志

Psammosilene tunicoides is one of the main ingredients of the "Yunnan Baiyao". P. tunicoides is an endangered species included in the secondary protection list in China Plant Red Data Book as well as the endemic species in Southwest China. Its natural resources could not meet the needs of pharmaceutical production. Construction of core collection of P. tunicoides will lay the foundation for germplasm improvement and molecular breeding. The sequence variation of the key enzymes gene locus (β-AS) were carried out to survey the population structure and population history of the species. Among the 11 populations across its geographical range, 36 haplotypes were identified. The levels of haplotype diversity (Hd=0.905) were high, while the levels of population differentiation (GST=0.280) were low. Analysisof molecular variance (AMOVA) indicated that a significantly greater proportion of total genetic variationpartitioned among populations thanwithin populations (values of 77.43% and 22.57%, respectively). These results in combination with the star-like phylogenetic network analysis indicate that Hap1 as an ancestral haplotypewas shared in four populations, Hap2, Hap4, Hap15 and Hap16 are occurred in two populations, the remains as private haplotype only distributed in single population. The strategy of core collection was constructed in order to maximumpreserve genetic diversity of P. tunicoides.

Advance in studies on TRPV1 and analgesic effect of traditional Chinese medicines / 中国中药杂志

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective positive ion channel that is mainly expressed in sensory neurons and a member of transient receptor potential (TRP) family. The receptor could be activated by mechanical irritation, chemical irritation or endogenous ligand to mediate pains and cause injury to body functions. Traditional Chinese medicine believes that the mechanism of pain is that "stagnation leads to pain". Specifically, both of the contracture and tautness caused by cold and the blood stasis could result in blood impassability and pain. Most of traditional Chinese medicines for clearing heat and removing toxicity have the anti-inflammatory effect, while those for warming interior, and promoting blood circulation to remove blood stasis have the effect in smoothening blood vessels. Therefore, either with the anti-inflammatory effect or the effect in smoothening blood vessels, traditional Chinese medicines for clearing heat and removing toxicity, warming interior, and promoting blood circulation have the analgesic effect In this paper, the authors summarize the analgesic effect of the above three traditional Chinese medicines, with TRPV1 as the target.

Serum 25(OH)D and lipid levels in Chinese obese and normal weight males before and after oral vitamin D supplementation / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the effect of oral vitamin D (VD) supplementation on VD status and serum lipid in Chinese obese and healthy normal-weight men.</p><p><b>METHODS</b>Twenty-one obese men with their body mass index (BMI)>28 kg/m(2) served as an obese group and 22 healthy normal-weight men with their BMI<24 kg/m(2) served as a control group in this study. After they were given 50 000 IU of oral VD, once a week for 8 weeks, the serum 25-hydroxyvitamin D [25(OH)D] concentration was measured with an enzyme-immunoassay kit.</p><p><b>RESULTS</b>After oral VD supplementation, the serum 25(OH)D concentration significantly increased from 46.1±9.1 nmol/L to 116.7±20.3 nmol/L in the obese subjects (P<0.01) and from 52.8±17.8 nmol/L to 181.3±30.2 nmol/L in the control ones (P=0.13). The serum high-density lipoprotein cholesterol (HDL-C) level was reduced within the normal reference range in the obese group. However, no significant change was observed in the level of other serum lipids (triglycerides, total cholesterol, and low-density lipoprotein cholesterol) in either of the two groups.</p><p><b>CONCLUSION</b>The effect of high-dose oral VD supplementation is weaker on VD status in the obese group than in the control group. High-dose oral VD supplementation has no side effect on serum lipid level in obese and control groups.</p>

Effect of ingredients of Astragalus-Salvia compound on vascular endothelial cell in placenta and vascular endothelial growth factor mRNA expression in trophocyte in pregnant rats with inhibited nitric oxide synthesis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the molecular mechanisms of effective ingredients of Astragalus-Salvia compound (ASC) in increasing placental blood supply, to provide thought for establishing an effective prevention and treatment of insufficient placental blood supply caused complications of pregnancy.</p><p><b>METHODS</b>The effective ingredients of ASC was isolated and abstracted and the rat model of inhibited nitric oxide synthesis was established by using L-Arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor. The mRNA expression of vascular endothelial growth factor (VEGF) in placental trophocyte and primordial micrangial endothelial cell was determined by using in situ hybridization at 12th day of pregnancy.</p><p><b>RESULTS</b>The VEGF mRNA expression was significantly lower in nitric oxide synthesis inhibited model rats than that in rats non-modeled, or in model rats treated by ASC abstracts or nitroglycerin (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Effective ingredients of ASC may improve VEGF mRNA expression in placental trophocyte and vascular endothelial cell in early pregnancy, and thus be favorable for placental vascular net formation, trophocyte infiltration and mother-placental circulation constitution for increasing placental blood supply to prevent and treat the insufficient placental blood supply caused diseases such as pregnancy-induced hypertension syndrome.</p>