Progress in research methods or strategies of compatibility mechanism of traditional Chinese medicine prescriptions / 中国药房

Compound formulas of traditional Chinese medicines （TCM）， also known as prescription in clinic， refers to a form of medication in which several TCMs are selectively combined according to the certain compatibility principles and the needs of patient’s condition， based on syndrome differentiation and treatment. At present， the methods and strategies for investigating the compatibility mechanisms of TCM prescriptions mainly focus on the following two aspects: analysis of pharmacological substances （including chemical composition analysis of TCM， ingredients of TCM analysis in blood， and pharmacokinetic analysis） and pharmacological signaling pathways analysis （involving network pharmacology analysis， signal pathway indicator detection， and metabolomics analysis）. In future research， the compatibility relationships of TCM prescriptions should be explored according to the principles of “Qiqing Hehe”，“ Shengjiang Fuchen”，“ Junchen Zuoshi”， and “Siqi Wuwei”. The regularity of TCM prescriptions compatibility should be shown in the change regularity of chemical components， pharmacokinetics， pharmacological pathways， and chemical compositions of various ratios of TCMs. Based on the insurance of holistic efficacy of TCM prescriptions， the underlying mechanisms of compatibility should be uncovered， which will provide references for the optimization of clinical applications of prescriptions and new directions for the creation of innovative TCM prescriptions.

"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.@*METHODS@#The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.@*RESULTS@#Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).@*CONCLUSION@#Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups / 中草药·英文版

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its “pharmacodynamic group”. By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the “pharmacodynamic group” for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and “pharmacodynamic group”, it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and “pharmacodynamic group” in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and “pharmacodynamic group”.

Investigation of Pharmacodynamic Material Basis and Mechanism of Qianyang Yuyin Granules Against Hypertensive Renal Damage Based on LC/Q-TOF-MS and Network Pharmacology / 中国实验方剂学杂志

Objective:To systematically study the chemical components of Qianyang Yuyin granules and explore its main pharmacodynamic substances and mechanism in the prevention and treatment of hypertensive renal damage. Method:Liquid chromatography coupled with quadrupole time-of-flight mass spectrometry （LC/Q-TOF-MS） was employed to comprehensively analyze the chemical components of Qianyang Yuyin granules. Agilent Poroshell 120 SB-C₁₈ column （3.0 mm×100 mm， 2.7 μm） was used， flow rate was 0.4 mL·min^-1， electrospray ionization （ESI） was applied and operated in positive and negative ion modes， the acquisition range was <italic>m</italic>/<italic>z</italic> 25-1 000. Mobile phase in positive ion mode consisted of water+10 mmol·L^-1 ammonium formate+0.125% formic acid+0.1% methanol （A）-［acetonitrile-water （9∶1）+10 mmol·L^-1 ammonium formate+0.125% formic acid］ （B）， and in negative ion mode consisted of water+10 mmol·L^-1 ammonium formate+0.1% methanol （A）-［acetonitrile-water （9∶1）+10 mmol·L^-1 ammonium formate］ （B） with the gradient elution （0-3.5 min， 5%B； 3.5-4 min， 5%-10%B； 4-9 min， 10%-25%B； 9-18 min， 25%-30%B； 18-25 min， 30%-50%B； 25-27 min， 50%-90%B； 27-32 min， 90%B； 32-33 min， 90%-5%B； 33-39 min， 5%B）. According to the information of the accurate mass， the multistage fragment ions， the mass spectrometric data of the standard substances and the relative reference literature， the structures of the chemical components in Qianyang Yuyin granules were identified. Based on the identified components， network pharmacology study， including target prediction and functional enrichment was applied to screen out the main active substances against hypertensive renal damage， and explore the potential mechanism. Result:A total of 99 chemical components were identified， from which 43 active substances and 48 key targets were screened out. The key components contained kaempferol， quercetin， ferulic acid， luteolin， caffeic acid methyl ester， cinnamic acid， aloe-emodin， emodin， gallic acid， <italic>N</italic>-<italic>trans</italic>-feruloyltyramine， isoorientin， 8-<italic>O</italic>-feruloylharpagide， ethyl caffeate， isookanin， cyasterone， 2，3，5，4'-tetrahydroxystilbene-2-<italic>O</italic>-<italic>β</italic>-<italic>D</italic>-glucopyranoside， loganin， alisol B-23-acetate and harpagide. The key targets included vascular endothelial growth factor A （VEGFA）， serine/threonine protein kinase 1 （AKT1）， Jun proto-oncogene （JUN）， etc. Conclusion:Qianyang Yuyin granules mainly exert the effects of removing heat from the liver， tonifying the kidney and removing blood stasis via modulation of vascular endothelium， angiogenesis， inflammatory reaction， oxidative stress， immune response and so on.

Isolation and Elucidation of a Novel Isoquinoline Alkaloid from Corydalis hendersonii / 中国实验方剂学杂志

As part of systematic research of Corydalis hendersonii,a typical traditional Tibetan herbal medicine with clearing heat,relieving pain,and lowering blood pressure effects,a novel isoquinoline alkaloid,named hendersine G was isolated from the ethanol extract of the whole plant by various chromatographic techniques,including silica gel column,reverse phase column (ODS),Sephadex LH-20,and semi-preparative HPLC.Its structure was elucidated by MS,NMR and other spectroscopic data analysis.Hendersine G can be regarded as a condensation product of a tetrahydroberberine and a succinic acid,however,its absolute configuration has not been determined due to its structural complexity and less obtained amount.This present study provides an inspiration for further exploration of novel molecules from C.hendersonii.

Application progress on model organism zebrafish in screening of pharmacodynamic substances of Chinese materia medica / 中草药

Compared with mammals, zebrafish has unique advantages in screening pharmacoactive substance, and has been paid more and more attention in the field of medicine. In recent years, the exploration of zebrafish has been extended and extended to the field of Chinese materia medica (CMM), especially for the screening pharmacoactive substance of the single CMM, the CMM compound and Chinese patent medicines with multi-target, multi-channel and multi-link effects. As a complete animal model, zebrafish can carry out comprehensive and deep research on the effective chemical components that play a role in TCM, and then realize convenient, rapid and high-throughput screening of pharmacodynamics substances in CMM. Combined with the literature reports in recent five years at home and abroad, this paper reviews the latest research progress and unique advantages on the screening of pharmacodynamics substances in CMM in model organism zebrafish, mainly from the screening of cardiovascular drugs, lipid-lowering and liver-protecting drugs, anti-osteoporosis drugs, anti-tumor drugs, anti-inflammatory and other drugs, in order to provide a new idea for the application of model organism zebrafish in CMM and provide reference for the new drugs research of CMM.

The Research of Modern Pharmacodynamic Material Basis Based on the Traditional Efficacy of Traditional Chinses Medicine is the Source for Original Research / 世界科学技术-中医药现代化

The traditional efficacy of traditional Chinese medicine (TCM) is to summarize the clinical efficacy of TCM under the guidance of TCM theory,and it possess important guiding significance for the clinical use of TCM.Comparing with the modern medical system,the TCM system was different from western medicine in diagnosis and treatment modes,and the disease targets of TCM maybe more extensive than that of western medicine.Based on the traditional efficacy of TCM,combined with modern means of science and technology,the research on material basis and pharmacological mechanism of TCM was beneficial to discovery the new targets,new mechanism,new material and the secondary development of new drug of TCM.Furthermore,it also has far-reaching significance on interpret the modern scientific connotation of TCM efficacy.Therefore,deriving from the traditional efficacy of TCM,the research of modern pharmacodynamic material basis is the source for original research.

Effective Forms, Additive Effect, and Toxicities Scattering Effect of Pharmacodynamic Substances of TCMs Some Reflections Evoked by the Study on the Metabolic Disposition of Traditional Chinese Medicines (TCM) / 世界科学技术-中医药现代化

The blood concentrations of the pharmacodynamic substances of traditional Chinese medicines (TCMs) are usually very low. How can they exert pharmacological actions, in which forms (original form, metabolite or the both) do they exert the actions. To answer these questions, we proposed a new concept ofEffective Formsof pharmacodynamic substances of TCMs and a hypothesis of additive effect of multiple constituents of TCMs. The hypothesis includes that the aggregate or summation of Effective Forms of pharmacodynamic substances of TCMs is the core material base of the effi-cacy of TCMs, and the additive effect of the blood concentrations of different Effective Forms is one part of the action mechanism. The additive effect of the different Effective Forms of a TCMs means an additive effect of numerous con-stituents or/and metabolites on a same target, and therefore the efficacy brought by the addition of the concentrations of all these compounds, which different from the synergy effect of multi-constituents on multi-targets. Studies on the disposition of TCMs showed that a constituent can be biotransformed to many metabolites (up to more than 50 metabolites);different constituents can produce the same metabolites;many metabolites (up to 10 compounds for each metabolite) are isomers or homologues; some constituents can be converted to each other in vivo; and some metabolites are bioactive. These com-pounds having the similar structure are likely to have the same pharmacological effects on the same target, which could provide experimental evidences for the concept ofEffective Formsand the hypothesis ofAdditive Effect. We suggest that the Effective Forms and Additive Effects of the pharmacodynamic substances of TCMs should be extensively investi-gated in the future, and the results of such researches will help us further understand the pharmacodynamic substances and action mechanism of TCMs, and give a new explanation 'Toxicities Scattering Effect' for 'Why the toxicities of TCMs are low', and propose a new strategy for quality control of TCMs.