Molecular Mechanisms of Notopterygii rhizoma Et Radix for Treating Arrhythmia Based on Network Pharmacology.

OBJECTIVE: To explore the possible mechanism for treating NRR in arrhythmia using network pharmacology and molecular docking in this study. METHODS: Active compounds and targets for NRR were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, SymMap, and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Arrhythmia-related genes were acquired from the Comparative Toxicogenomics Database (CTD) and the GeneCards database. Overlapping targets of NRR associated with arrhythmia were acquired and displayed via a Venn diagram. DAVID was applied for GO and KEGG pathway analyses. Cytoscape software and its plug-in were used for PPI network construction, module division and hub nodes screening. Auto- Dock Vina and qRT-PCR were carried out for validation. RESULTS: In total, 21 active compounds and 57 targets were obtained. Of these, coumarin was the predominant category which contained 15 components and 31 targets. There were 5 key targets for NRR in treating arrhythmia. These targets are involved in the apoptotic process, extrinsic apoptotic signaling pathway in the absence of ligand, and endopeptidase activity involved in the apoptotic process by cytochrome c. The main pathways were the p53 signaling pathway, Hepatitis B and apoptosis. The molecular docking and qRT-PCR displayed good effects on hub node regulation in NRR treatment. CONCLUSION: NRR plays an important role in anti-apoptotic mechanisms that modulate the p53 signaling pathway, which may provide insight for future research and clinical applications focusing on arrhythmia therapy.

Herbal Textual Research on Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix in Famous Classical Formulas / 中国实验方剂学杂志

By reviewing ancient materia medica， prescription and medical books， combined with modern literature， the paper made textual research on the name， origin， producing area， quality evaluation， harvesting and processing methods of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix， so as to provide a basis for the selection and use of these two herbs in the development of famous classical formulas. Through textual research， it can be found that Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix were mixed together in the early history of China， but the distinction was first made during the Southern and Northern dynasties， and since then there have been constant controversies， and it is not until contemporary times that they are distinguished clearly. In the past dynasties， Duhuo and Qianghuo were used as the rectification of names， some aliases and trade names were also seen. Angelica biserrata is the mainstream origin of Angelicae Pubescentis Radix in the past dynasties， and there are many plants belonging to Angelica， Heracleum and Aralia， which are also used as this medicine. However， the origin of Notopterygii Rhizoma et Radix used in the past dynasties is mostly Notopterygium incisum or N. franchetii， which is relatively uniform. The producing areas of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix are mostly concentrated in the western and northwestern regions of China， among which Angelicae Pubescentis Radix is mainly produced in Hubei， Chongqing， Sichuan， Shaanxi and other places， and the border area between Hubei and Chongqing is the geo-authentic area. Notopterygii Rhizoma et Radix is mainly produced in Sichuan， Gansu， Qinghai， Shaanxi and others with the western and northern Sichuan and southern Gansu as the geo-authentic areas. Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix in the past dynasties were harvested in spring and autumn， especially in February and August of the lunar calendar. Angelicae Pubescentis Radix with strong main roots， few branches， firm texture and strong aroma is superior， and Notopterygii Rhizoma et Radix with strong rhizomes， tightly raised knots， purple-brown skin， tight cross-section， strong aroma and silkworm-like shape is superior. The processing methods of Angelicae Pubescentis Radix and Notopterygii Rhizoma et Radix are mostly cut after cutting the reeds， and the raw product is used as medicine. Based on the above research results， it is recommended that the roots of A. biserrata should be used for Angelicae Pubescentis Radix and the roots of N. incisum should be used for Notopterygii Rhizoma et Radix in the development of famous classical formulas， and raw products should be used in the formulas that do not specify processing requirements.

Rapid and intelligent discrimination of Notopterygium incisum and Notopterygium franchetii by infrared spectroscopic fingerprints and electronic olfactory fingerprints.

This preliminary research evaluated mid-infrared (MIR) spectroscopy, near-infrared (NIR) spectroscopy and electronic nose (E-nose) for the rapid identification of Notopterygium incisum and Notopterygium franchetii, which were both approved sources of Notopterygii Rhizoma et Radix (Chinese Pharmacopoeia, 2015) but possessed different chemical compositions and pharmacological activities. At the level of single variables, MIR showed quite a few discriminating peaks in the regions of 3000-2800 cm-1 (the stretching bands of CH), 1770-1670 cm-1 (the stretching bands of CO), and 1400-1200 cm-1 (the bending bands of CH and the stretching bands of CO). Meanwhile, NIR only showed an intuitive discriminating peak near 4736 cm-1 (the combination band of OH and CO stretching modes). E-nose response signals of N. incisum and N. franchetii were significant different (p < 0.05) on four sensors, i.e., LY2/LG, LY2/GH, LY2/gCT and LY2/gCTI. Using the infrared spectra or E-nose sensor responses as fingerprints, support vector machine (SVM) models can provide good recognition accuracy (100% for MIR and NIR models, 92.9% for E-nose model). This research indicated the feasibility of MIR, NIR and E-nose for the accurate, rapid, cheap and green identification of N. incisum and N. franchetii, which was desirable to assure the authenticity, efficacy and safety of related herb materials and products.

HPLC Fingerprint Analysis of Notopterygii Rhizoma et Radix with Different Commercial Specifications / 中国实验方剂学杂志

Objective: To establish HPLC fingerprint of Notopterygii Rhizoma et Radix with different commercial specifications and to provide the basis for the division of commercial grades and the quality control of Notopterygii Rhizoma et Radix on the market. Method: The market investigation and literature research were used to understand the existing situation of Notopterygii Rhizoma et Radix goods.Notopterygii Rhizoma et Radix goods were divided into three commercial specifications according to the source and appearance,such as Canqiang,Tiaoqiang and Datouqiang.Fingerprint of Notopterygii Rhizoma et Radix with different commercial specifications was established by HPLC-PDA,the mobile phase was consisted of acetonitrile-0.3% acetic acid in a gradient elution mode.Similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine(version of 2004A) was used to confirm the common peaks and evaluate the similarity.SPSS 19.0 statistical software was used to make principal component analysis(PCA) for HPLC fingerprint pattern. Result: The common mode of fingerprint for Canqiang,Tiaoqiang and Datouqiang were established separately.A total of 22 common peaks were marked in Canqiang,23 common peaks were marked in Tiaoqiang,29 common peaks were marked in Datouqiang.The result of similarity evaluation and PCA showed that the quality of Notopterygii Rhizoma et Radix with the same commercial specification was stable.There were great differences in chemical compositions and their contents among Notopterygii Rhizoma et Radix with different commercial specifications. Conclusion: The fingerprint method can well distinguish commercial specifications of Notopterygii Rhizoma et Radix,and it can provide the basis for the division of commercial grades and the quality control of Notopterygii Rhizoma et Radix.

Simultaneous quantification of 33 active components in Notopterygii Rhizoma et Radix using ultra high performance liquid chromatography with tandem mass spectrometry.

A method of ultra high performance liquid chromatography with tandem mass spectrometry was developed for the simultaneous quantification of 33 active components including 26 coumarins and 7 phenolic acid esters in Notopterygii Rhizoma et Radix (NRR). Chromatographic separation was achieved on a Kinetex® C18 column (100 mm × 2.1 mm i.d.; 2.6 µm) with a gradient elution in 18 min. Electrospray ionization tandem mass spectrometric detection was conducted in the positive and negative ionization modes with multiple reaction monitoring. All of 33 analytes showed good linearity (R2 ≥ 0.9919) within the test range. The relative standard deviations of the precision, repeatability and stability were not exceeding 4.97%, and the recoveries were in the range of 85.37%-115.00%. The matrix effect on the response of target analyte was not obvious. The validated method was successfully applied to quantify the 33 components in ten batches of NRR samples. Quantitative results showed the coumarins and phenolic acid esters with large difference in level of content in the herb samples. Furthermore, hierarchical cluster analysis and principal component analysis were applied to classify and discriminate these samples. The variations of isoimperatorin, notopterol, bergamottin, nodakenin, phenethylferulate were suggested as important indicators of NRR quality. This work may serve for quality identification and comprehensive evaluation of NRR.

[Industrialization condition and development strategy of Notopterygii Rhizoma et Radix].

Notopterygii Rhizoma et Radix, the underground part of Notopterygium incisum and N. franchetii, is used as a classical traditional Chinese medicine, and as raw materials for 262 Chinese patent drugs production in 694 pharmaceutical factories currently. It plays an important role in the whole Chinese medicine industry with irreplaceable important economic and social values. However, wild resource of was abruptly depleted, and large-scale artificial cultivation has been inapplicable. In this study, Utilization history and the industrialization status of Notopterygii Rhizoma et Radix were summarized. Resource distribution, ecological suitability of Notopterygii Rhizoma et Radix and core technologies for seeds production, seedling breeding, large-scale cultivation has been reported by current studies, and basic conditions are already available for industrialization production of Notopterygii Rhizoma et Radix. However, there still some key technical problems need to be solved in the further research, and some policy dimensions need to be focused on in the coming industrialization cultivation of Notopterygii Rhizoma et Radix.

[Standardization of production of process Notopterygii Rhizoma et Radix slices].

Notopterol, isoimperatorin, volatile oil and extract （water and ethanol) were used as the research objects in this study to investigate the effects of different softening method, slice thickness and drying methods on the quality of Notopterygii Rhizoma et Radix slices, and the experimental data were analyzed by homogeneous distance evaluation method. The results showed that different softening, cutting and drying processes could affect the content of five components in Notopterygii Rhizoma et Radix incisum. The best processing technology of Notopterygii Rhizoma et Radix slices was as follows: non-medicinal parts were removed; mildewed and rot as well as moth-eaten parts were removed; washed by the flowing drinking water; stacked in the drug pool; moistening method was used for softening, where 1/8 volume of water was sprayed for every 1 kg of herbs every 2 h; upper part of herbs covered with clean and moist cotton, and cut into thick slices (2-4 mm) after 12 h moistening until appropriate softness, then received blast drying for 4 h at 50 ℃, and turned over for 2 times during the drying. The process is practical and provides the experimental basis for the standardization of the processing of Notopterygii Rhizoma et Radix, with great significance to improve the quality of Notopterygii Rhizoma et Radix slices.

Industrialization condition and development strategy of Notopterygii Rhizoma et Radix / 中国中药杂志

Notopterygii Rhizoma et Radix, the underground part of Notopterygium incisum and N. franchetii, is used as a classical traditional Chinese medicine, and as raw materials for 262 Chinese patent drugs production in 694 pharmaceutical factories currently. It plays an important role in the whole Chinese medicine industry with irreplaceable important economic and social values. However, wild resource of was abruptly depleted, and large-scale artificial cultivation has been inapplicable. In this study, Utilization history and the industrialization status of Notopterygii Rhizoma et Radix were summarized. Resource distribution, ecological suitability of Notopterygii Rhizoma et Radix and core technologies for seeds production, seedling breeding, large-scale cultivation has been reported by current studies, and basic conditions are already available for industrialization production of Notopterygii Rhizoma et Radix. However, there still some key technical problems need to be solved in the further research, and some policy dimensions need to be focused on in the coming industrialization cultivation of Notopterygii Rhizoma et Radix.

[Correspondence analysis between traditional commercial specifications and quantitative quality indices of Notopterygii Rhizoma et Radix].

This paper aims to explore a comprehensive assessment method combined traditional Chinese medicinal material specifications with quantitative quality indicators. Seventy-six samples of Notopterygii Rhizoma et Radix were collected on market and at producing areas. Traditional commercial specifications were described and assigned, and 10 chemical components and volatile oils were determined for each sample. Cluster analysis, Fisher discriminant analysis and correspondence analysis were used to establish the relationship between the traditional qualitative commercial specifications and quantitative chemical indices for comprehensive evaluating quality of medicinal materials, and quantitative classification of commercial grade and quality grade. A herb quality index (HQI) including traditional commercial specifications and chemical components for quantitative grade classification were established, and corresponding discriminant function were figured out for precise determination of quality grade and sub-grade of Notopterygii Rhizoma et Radix. The result showed that notopterol, isoimperatorin and volatile oil were the major components for determination of chemical quality, and their dividing values were specified for every grade and sub-grade of the commercial materials of Notopterygii Rhizoma et Radix. According to the result, essential relationship between traditional medicinal indicators, qualitative commercial specifications, and quantitative chemical composition indicators can be examined by K-mean cluster, Fisher discriminant analysis and correspondence analysis, which provide a new method for comprehensive quantitative evaluation of traditional Chinese medicine quality integrated traditional commodity specifications and quantitative modern chemical index.

Correspondence analysis between traditional commercial specifications and quantitative quality indices of Notopterygii Rhizoma et Radix / 中国中药杂志

This paper aims to explore a comprehensive assessment method combined traditional Chinese medicinal material specifications with quantitative quality indicators. Seventy-six samples of Notopterygii Rhizoma et Radix were collected on market and at producing areas. Traditional commercial specifications were described and assigned, and 10 chemical components and volatile oils were determined for each sample. Cluster analysis, Fisher discriminant analysis and correspondence analysis were used to establish the relationship between the traditional qualitative commercial specifications and quantitative chemical indices for comprehensive evaluating quality of medicinal materials, and quantitative classification of commercial grade and quality grade. A herb quality index (HQI) including traditional commercial specifications and chemical components for quantitative grade classification were established, and corresponding discriminant function were figured out for precise determination of quality grade and sub-grade of Notopterygii Rhizoma et Radix. The result showed that notopterol, isoimperatorin and volatile oil were the major components for determination of chemical quality, and their dividing values were specified for every grade and sub-grade of the commercial materials of Notopterygii Rhizoma et Radix. According to the result, essential relationship between traditional medicinal indicators, qualitative commercial specifications, and quantitative chemical composition indicators can be examined by K-mean cluster, Fisher discriminant analysis and correspondence analysis, which provide a new method for comprehensive quantitative evaluation of traditional Chinese medicine quality integrated traditional commodity specifications and quantitative modern chemical index.