An Exploration in the Potential Substance Basis and Mechanism of Chuanxiong Rhizoma and Angelicae Dahuricae Radix on Analgesia Based on Network Pharmacology and Molecular Docking

Objective:The objective was to study the potential substance basis and action mechanism of Chuanxiong Rhizoma(CX)and Angelicae Dahuricae Radix(AD)on analgesia through network pharmacology and molecular docking.Materials and Methods:The active components and targets of CX and AD and pain-related genes were retrieved through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and GeneCards database.Then,the co-action targets were found,protein–protein interaction network was constructed by the String database.The Cytoscape 3.7.1 was used to construct"CX-AD-active components-pain"network.Further enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)was carried out to predict its mechanism of action,the top four active components in the network were docked with the targets.Results:There are 26 compounds,45 targets in the network.Among them,(Z)-ligustilide and beta-sitosterol,respectively,have more potential targets in CX and AD,and prostaglandin-endoperoxide synthase(PTGS2),PTGS1 have more ligands.GO analysis shows that molecular functions of CX and AD mainly performed through the G protein-coupled amine receptor activity,adrenergic receptor activity,and catecholamine binding.KEGG analysis indicates that they could exert analgesic effect on the pathways of regulating neuroactive ligand-receptor interaction,serotonergic synapse,and cGMP-PKG signaling pathway.Molecular docking results show that the active compounds are highly compatible with the structure of the protein receptor,and they interact through the hydrogen bond andπ–πbond between the ligand and the active site residues.Conclusions:Through network pharmacology and molecular docking,this study preliminarily revealed the main active components,targets,and potential regulation network of CX and AD,providing a reference for the subsequent experimental research.

禹白芷中香豆素成分的HPLC-MS/MS分析

The main constituents of the extract from Yubaizi (the roots of Angelica dahurica)were analyzed by HPLC-MS/MS method,and a total of six cumarins were unequivocally determined.The fragmentation patterns of the cumarins were found useful for their characterization,and the relative contents of the six compounds were also calculated.

Explore the direct and/or the synergistic antihypertensive effects of wind-dispelling herbs involving Fangfeng and Baizhi on hypertensive rats with liver-yang hyperactivity based on vasoactive substances

Objective： To explore the direct and/or the enhancing antihypertensive effects of wind-dispelling herbs involvingFangfeng （Saposhnikoviae Radix） and Baizhi （Angelicae dahuricae Radix） using liver-yang hyperactivity renalhypertension rat. Methods： Model rats with hyperactivity of liver-yang hyperactivity were prepared using male SD rats.Once successful, the rats were randomly divided into groups and given medicine by gavage for 4 weeks. Blood wascollected from the abdominal aorta to prepare serum. Serum nitric oxide （NO） concentration was determined bychemical colorimetry. The contents of ET, TXB2 and 6-K-PGF1a were determined by enzyme linked immunosorbentassay （ELISA）. Results： Compared with the control model group, the blood pressure, serum ET and TXB2 of rats in thewind dispelling medicine group was not significantly reduced, while those of rats in captopril group, Tianma GoutengDecoction I group （TGD group） decreased significantly （P 〈0.05 for both）. Interestingly, the blood pressure, serum ETand TXB2 of rats in the combination group （wind dispelling medicine ＆ TGD） decreased significantly compared withboth wind dispelling medicine group and TGD group. Meanwhile, the levels of serum NO and 6- K-PGF1a in thecombination group was much higher than those in the wind dispelling medicine group or TGD group （P 〈0.05 for both）.However, the levels of serum NO and 6- K-PGF1a in the wind dispelling medicine group was not significantly increasedcompared with the model group. Conclusion： There is no direct pressure lowering effects of wind dispelling medicinealone, while wind dispelling medicine could potentiates the antihypertensive effects of Tianma Gouteng Decoction I.Besides, the synergistic effects may be related to decreased ET and TXB2 levels and the increased NO and 6- K-PGF1alevels.

Neolignan glycoside from Angelica dahurica

A new neolignan glycoside, 4-O-β-d-glucopyranosyl-9-O-β-d-glucopyranosyl-(7R,8S)-dehydrodiconiferyl alcohol was isolated from the fresh roots of Angelica dahurica. The structure of the new compound was elucidated on the basis of spectral analysis.

Fluorescence enhancement of radix angelica dahurica by binding to single silver sphere

We present a theoretical study of the influence of a single silver sphere on the fluorescence of radix angelica dahurica, which is a kind of traditional Chinese medicine. The enhancement factors of the excitation and the relaxation processes are deduced. The excitation can be enhanced more than 100 times at 315 nm. The enhancement factor of the emission can reach up to 9 at a center wavelength of 400 nm.

Potential Mechanism of Herb-Drug Interaction Mediated by Angelica dahurica: Inhibition on CYP3A Enzymes in Rats

Angelica dahurica is commonly referred to as ‘Baizhi’ in China and has been noted for its therapeutic significance. The major active ingredients of Angelica dahurica is coumarin, which is reported as a kind of potent inhibitor of cytochrome P450 enzymes (CYP450s). The aim of this study was to investigate the inhibition of CYP3A enzymes by total coumarin extract (TCE) obtained from dried root of Angelica dahurica by using in situ single pass intestinal perfusion (SPIP) and in situ liver perfusion in rats. When midazolam (MDZ) which is a substrate of CYP3A co-perfused with TCE (198 μg/mL) from Baizhi in duodenum and ileum segments, the Peff of MDZ has increased significantly compared with the MDZ single perfused group (p 0.05) (n = 6). During in situ liver perfusion study, the results demonstrated that, 3 days oral administration of TCE obtained from Baizhi could significantly reduce the elimination rate of MDZ in the perfusate (p Angelica dahurica extract co-administrated with drugs which are the substrates of CYP3A, much more attention should be paid rather than that of other CYP450 enzymes. These findings may facilitate in predicting possible herb-drug interactions (HDIs) when Angelica dahurica is used in combination with other drugs, and decrease the incidence of the CYP450-mediated HDIs.

Effects of Angelica dahurica on obesity and fatty liver in mice

Angelica dahurica(A. dahurica) is a traditional Chinese medicinal plant being used in clinical practice. The present study demonstrated that A. dahurica could reduce white-fat weight in high-fat-diet hyperlipidemic mice, decrease total cholesterol and triglyceride concentrations in the livers of both high-fat-diet and Triton WR1339 induced hyperlipidemic mice, and enhance the total hepatic lipase activities of them. These findings were further supported by the results derived from the experiments with Hep G2 cells in vitro. In addition, the proteins related to lipids metabolism were investigated using LC-MS/MS, indicating that genes of lipid metabolism and lipid transport were regulated by A. dhurica. The results from LC-MS/MS were further conformed by Western blot and real time PCR assays. A. dahurica could down-regulate the expression of catalase(CAT) and sterol carrier protein2(SCP2) and up-regulate the expression of lipid metabolism related genes-lipase member C(LIPC) and peroxisome proliferator-activated receptor gamma(PPARγ). In the Triton WR1339 mouse liver and Hep G2 cells in vitro, A. dahurica was able to increase the expression of LIPC and PPARγ, confirming the results from in vivo experiments. Imperatorin showed the same activity as A. dahurica, suggesting it was one of the major active ingredients of the herb. In conclusion, our work represented a first investigation demonstrating that A. dahurica was able to regulate lipid metabolism and could be developed as a novel approach to fighting against fatty liver and obesity.

New coumarin glucopyranosides from roots of Angelica dahurica

Objective： To investigate the chemical constituents from the roots of Angelica dahurica.Methods： The chemical constituents were isolated and purified by AB-8 macroporous adsorption resin and Sephadex LH-20 column as well as semi-preparative reversed phase HPLC.The chemical structures were identified by spectral data.Results： Ten compounds were isolated and identified as xanthoarnol-3-O-β-d-glucopyranoside（1）,angedahuricoside A（2）,angedahuricoside B（3）,isofraxidin-7-O-β-d-glucopyranoside（4）,fraxidin-8-O-β-d-glucopyranoside（5）,（-）-marmesinin（6）,（2 S,3 R）-3-hydroxymarmesinin（7）,hyuganoside V（8）,daucosterol（9）,and sucrose（10）.Conclusion： Compounds 1 –3 are new ones and compounds 4 –6 and 8 are obtained from title plant for the first time.

Seven new 3,4-dihydro-furanocoumarin derivatives from Angelica dahurica

Objective:To study the chemical constituents of the roots of Angelica dahurica,a well-known Chinese herbal medicine named Baizhi in Chinese.Methods:Compounds were separated by various chromatographies,and the structures of new compounds were elucidated based on the analysis of their spectroscopic and spectrometric data(1D,2D NMR,HRESI MS,IR,and UV).The absolute configurations of new compounds were determined by the calculated electronic circular dichroism and chemical derivatization.The inhibitory activities of all isolates against nitric oxide(NO)production were evaluated using lipopolysaccharide-activated RAW 264.7macrophage cells.Results:Seven new 3,4-dihydro-furanocoumarin derivatives(1a/1b,2a/2b,3a/3b,4)together with a known furanocoumarin(5)were isolated from the roots of A.dahurica.The new compounds included three pairs of enantiomers,(4S,2’’R)-angelicadin A(1a)/(4R,2’’S)-angelicadin A(1b),(4S,2’’S)-angelicadin A(2a)/(4R,2’’R)-angelicadin A(2b),and(4S,2’’S)-secoangelicadin A(3a)/(4R,2’’R)-secoangelicadin A(3b),together with(4R,2’’R)-secoangelicadin A methyl ester(4).The known xanthotoxol(5)inhibited the NO production with the half-maximal inhibitory concentration(IC50)value of(32.8±0.8)μmol/L,but all the new compounds showed no inhibitory activities at the concentration of100μmol/L.Conclusion:This is the first report of the discovery of 3,4-dihydro-furanocoumarins from A.dahurica.The results are not only meaningful for the understanding of the chemical constituents of A.dahurica,but also enrich the reservoir of natural products.