Application Regularity and Mechanism of Chinese Marine Drug Pair Haliotidis Concha-Oystreae Concha Based on Literature Mining Technology / 中国实验方剂学杂志

ObjectiveTo analyze the clinical application hotspots， development trends， compatibility characteristics， application rules， and formulation mechanisms of the Chinese marine drug pair Haliotidis Concha-Oystreae Concha in order to provide references for its clinical medication and further research. MethodBy means of various modern literature databases such as China National Knowledge Infrastructure （CNKI）， modern clinical prescriptions containing Haliotidis Concha-Oystreae Concha， as well as the clinical application hotspots， were retrieved， followed by visualized analysis of hotspots and development trends of their clinical applications using Citespace. The drug composition， efficacy and indications， and drug dosages in the prescriptions were statistically analyzed. Additionally， various statistical software including SPSS Modeler 18.0 were employed to analyze the indications， syndromes， and formulation rules of Haliotidis Concha-Oystreae Concha. ResultThe visualized analysis included 90 articles， revealing a gradual decrease in publications in this field in recent years. Key clinical application keywords were identified as hypertension， collateral deficiency producing wind， insomnia， etc. Eighty clinical prescriptions were retrieved， involving 121 drugs. Frequency analysis of compatibility demonstrated that the top 10 drugs were Uncariae Ramulus cum Uncis， Gastrodiae Rhizoma， Os Draconis， Achyranthis Bidentatae Radix， Paeoniae Radix Alba， Chrysanthemi Flos， Scutellariae Radix， Gardeniae Frucuts， Glycyrrhizae Radix et Rhizoma， and Polygoni Multiflori Caulis. Association rule analysis showed that core combinations included "Uncariae Ramulus cum Uncis-Achyranthis Bidentatae Radix" and "Os Draconis-Pheretima-Chuanxiong Rhizoma". Through factor reliability analysis， new drug combinations were derived， such as "Gastrodiae Rhizoma-Polygoni Multiflori Caulis-Eucommiae Cortex-Taxilli Herba-Leonuri Herba"， "Achyranthis Bidentatae Radix-Uncariae Ramulus cum Uncis"， "Scutellariae Radix-Glycyrrhizae Radix et Rhizoma-Margarita-Prunellae Spica"， "Os Draconis-Pheretima-Bombyx Batryticatus"， "Chrysanthemi Flos-Chuanxiong Rhizoma"， "Poria-Acori Tatarinowii Rhizoma"， and "Paeoniae Radix Alba-Gardeniae Fructus-Sclerotium Poriae Pararadicis". The Haliotidis Concha-Oystreae Concha drug pair was mainly used to treat diseases with liver Yang hyperactivity syndrome， with hypertension accounting for 40.00%， migraines for 30.00%， and dizziness for 15.00%. In the treatment of liver Yang hyperactivity syndrome， the main categories of compatible drugs were liver-pacifying and wind-extinguishing ones （19.86%）， blood-activating and stasis-resolving ones （12.13%）， and spirit-calming ones （10.08%）. High-frequency drugs in the prescriptions function to reduce blood pressure through multiple pathways， such as increasing nitric oxide （NO） levels， downregulating angiotensin Ⅱ （Ang Ⅱ）， and inhibiting angiotensin-converting enzyme （ACE）. ConclusionThrough comprehensive analysis of the results， the Haliotidis Concha-Oystreae Concha drug pair is commonly used for hypertension with liver Yang hyperactivity syndrome， and is often combined with deficiency-tonifying， liver-pacifying and wind-extinguishing， heat-clearing， and spirit-calming drugs， aiming to simultaneously extinguish wind， relieve spasms， and pacify the liver to subdue Yang， while also clearing heat to relax bowels， stabilizing the mind， and enhancing the liver-pacifying and Yang-subduing effects of this drug pair.

Mechanism of Carthami Flos and Lepidii Semen drug pair in inhibition of myocardial fibrosis by improving cardiac microenvironment based on network pharmacology and animal experiment / 中国中药杂志

Previously, Carthami Flos and Lepidii Semen(CF-LS) drug pair has been proved effective in inhibiting myocardial fibrosis(MF) by blunting the activity of cardiac fibroblasts. The present study explored the underlying mechanism of CF-LS in inhibiting MF by improving the cardiac microenvironment based on network pharmacology combined with experimental verification. Active compounds and potential targets of CF-LS were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the potential targets of MF were obtained from GeneCards, Online Mendelian Inheritance in Man(OMIM), and Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB). The "active component-target-MF" network was constructed and analyzed by Cytoscape 3.8.1. The protein-protein interaction(PPI) network was constructed by STRING. The Gene Ontology(GO) biological process enrichment analysis was performed by CluoGO plug-in. Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analysis was performed by R 4.0.2 and Funrich. Subsequently, the inhibitory effect of CF-LS on MF was investigated based on angiotensin Ⅱ(Ang Ⅱ)-induced MF rats. RT-PCR and ELISA were used to verify the effect of CF-LS on the targets of signaling pathways related to vascular endothelial cells predicted by the network pharmacology. Thirty-one active components and 204 potential targets of CF-LS, 4 671 MF-related targets, and 174 common targets were obtained. The network analysis showed that the key targets of CF-LS against MF included RAC-alpha serine/threonine-protein kinase(AKT1), transcription factor AP-1(JUN), mitogen-activated protein kinase 1(MAPK1), cellular tumor antigen p53(TP53), transcription factor p65(RELA), and mitogen-activated protein kinase 8(MAPK8). Biological processes mainly involved regulation of blood vessel diameter, regulation of blood vessel endothelial cell migration, cell death in response to oxidative stress, etc. Advanced glycation end products(AGE)-receptor for advanced glycation end products(RAGE) signaling pathway, phosphoinositide 3-kinase(PI3 K)-serine/threonine protein kinase(AKT) signaling pathway, hypoxia-inducible factor-1(HIF-1) signaling pathway, integrin signaling pathway, transforming growth factor-β(TGF-β) signaling pathway, etc. were involved in signaling pathway enrichment. Literature retrieval confirmed that some of these signaling pathways were closely related to vascular endothelial cells, including AGE-RAGE, PI3 K-AKT, HIF-1α, p53, the transcription factor activator protein-1(AP-1), integrin, p38 MAPK, and TGF-β. Animal experiments showed that CF-LS inhibited MF induced by Ang Ⅱ in rats by suppressing the expression of RAGE, HIF-1α, integrin β6, and TGF-β1. The inhibitory effect of CF-LS on MF has the characteristics of multiple components, multiple targets, and multiple pathways. CF-LS can inhibit MF by regulating the activity of vascular endothelial cells in the cardiac microenvironment.

Mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on intervention of cerebral ischemia based on network pharmacology-molecular docking / 中国中药杂志

Cerebral ischemia is one of the most common diseases in China, and the drug pair of Chuanxiong Rhizoma and Paeoniae Radix Rubra can intervene in cerebral ischemia to reduce the inflammatory response of cerebral ischemia and apoptosis. To reveal the intervention mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia systematically, computer network pharmacology technology was used in this paper to predict the target and signaling pathway of the drug pair on the intervention of cerebral ischemia, and then the molecular docking technology was used to further analyze the mechanism of the intervention. The target results were then verified by the rat cerebral ischemia model. The target network results showed that the active compounds of Chuanxiong Rhizoma-Paeoniae Radix Rubra for cerebral ischemic disease contained 30 compounds, 38 targets and 9 pathways. The main compounds included phenolic acids in Chuanxiong Rhizoma and monoterpene glycosides in Paeoniae Radix Rubra. The key targets involved mitogen-activated protein kinase 1(MAPK1), steroid receptor coactivator(SRC), epidermal growth factor receptor(EGFR), mitogen-activated protein kinase 14(MAPK14), caspase-3(CASP3), caspase-7(CASP7), estrogen receptor 1(ESR1), and mitogen-activated protein kinase 8(MAPK8), etc. The target gene functions were biased towards protein kinase activity, protein autophosphorylation, peptidyl-serine phosphorylation and protein serine/threonine kinase activity, etc. The important KEGG pathways involved Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. Molecular docking results showed that catechin, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin had strong binding ability with MAPK1, SRC, EGFR, MAPK14 and CASP7. MCAO rat experimental results showed that Chuanxiong Rhizoma-Paeoniae Radix Rubra significantly improved the cerebral ischemia injury and interstitial edema, and significantly reduced the activation of caspase-7 and the phosphorylation of ERK1/2. The Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair alleviated cerebral ischemia injury through a network model of multi-phenotype intervention by promoting cell proliferation and differentiation, reducing inflammatory factor expression, protecting nerve cells from death and figh-ting against neuronal cell apoptosis, with its action signaling pathway most related to Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. This study provides the basis for clinical intervention of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia, and also provides ideas for the modernization of drug pairs.

Analysis of medication regularity of classical prescription in treatment of COPD based on multi-target efficacy evaluation system of Chinese medicine / 中国中药杂志

Effective drugs for chronic obstructive pulmonary disease(COPD), a complex chronic lung disease, have long been difficultly determined, while traditional Chinese medicine(TCM) has played a critical effect in the treatment of such disease. A new approach for the prediction based on data analysis by integrating TCM basic theories and modern science is urgently needed apart from clinical experiments. In this study, an efficacy evaluation system of COPD was established based on the multi-target efficacy evaluation system of Chinese medicine to analyze the medication regularity and characteristics, such as efficacies, properties, meridian tropism,and core combinations of Chinese medicines. The characteristics of classical prescriptions in the intervention of COPD were explored from modern pharmacology. The results showed that the Chinese medicines in the classical prescriptions in the treatment of COPD were dominated by heat-clearing, phlegm-resolving, dampness-dispelling, exterior-releasing, deficiency-tonifying, and interior-warming drugs. Among them, dampness-dispelling, interior-warming, and heat-clearing drugs resulted in higher perturbation efficiency in the disease network than some western medicines on the market, suggesting that these drugs possessed better efficacies in the treatment of COPD. In the classic prescriptions, warm-heat drugs were equivalent to cold-cool drugs in number, while the proportion of warm-heat drugs gradually raised with the increase in the perturbation efficiency. Additionally, core combinations in the classical prescriptions,such as heat-clearing/heat-clearing, dampness-dispelling/dampness-dispelling, and phlegm-resolving/heat-clearing, could achieve better efficacy for COPD. The present study preliminarily screened out the efficacies of Chinese medicines in the treatment of COPD based on scientific data through the multi-target efficacy evaluation system to explore the effect of Chinese medicine on COPD from modern pharmacology, explain the mechanism of TCM treatment of lung diseases, and provide references for the development of drugs targeting COPD.

Mechanism of 'Invigorating Qi and Promoting Blood Circulation' Drug Pair Ginseng-Danshen on Treatment of Ischemic Heart Disease Based on Network Pharmacology / 中国结合医学杂志

OBJECTIVE@#Using network pharmacology to explore the mechanism of the 'invigorating qi and promoting blood circulation' drug pair Ginseng-Danshen (Salvia miltiorrhiza) on treatment of ischemic heart disease (IHD).@*METHODS@#The chemical constituents of ginseng and Danshen drug pair were identified by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential targets of the pair were identified. The pharmacodynamics of the pair was analyzed using network pharmacology. The targets of IHD were identified by database screening. Using protein-protein interaction network, the interaction targets of Ginseng-Danshen on IHD were constructed. A "constituent-target-disease" interaction network was constructed using Cytoscape software, Gene Ontology (GO) term enrichment analysis and biological pathway enrichment analysis were carried out, and the mechanism of improving myocardial ischemia by the Ginseng-Danshen drug pair was investigated.@*RESULTS@#Seventeen active constituents and 53 targets were identified from ginseng, 53 active constituents and 61 targets were identified from Danshen, and 32 protein targets were shared by ginseng and Danshen. Twenty GO terms were analyzed, including cytokine receptor binding, cytokine activity, heme binding, and antioxidant activity. Sixty Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were analyzed, including phosphatidylinositol 3-kinase-serine-threonine kinase (PI3K-AKT) signaling pathway, p53 signaling pathway, interleukin 17 signaling pathway, tumor necrosis factor signaling pathway, and the advanced glycation end product (AGE)-the receptor for AGE (RAGE) signaling pathway in diabetic complications.@*CONCLUSION@#The specific mechanism of Ginseng-Danshen drug pair in treating IHD may be associated with improving the changes of metabolites inbody, inhibiting the production of peroxides, removing the endogenous oxygen free radicals, regulating the expression of inflammatory factors, reducing myocardial cell apoptosis and promoting vascular regeneration.

Prescription rules for prescriptions containing Corydalis Rhizoma-Toosendan Fructus drug pair based on TCM inheritance support platform / 中草药

Objective: To explore the combination rule of Corydalis Rhizoma-Toosendan Fructus drug pair through the research in "Pharmaceutical Standard of the Ministry of Health of the People's Republic of China-Traditional Chinese Medicine Formulation", so as to provide theoretical basis for clinical application and new product development of this pair. Methods: The prescriptions containing Corydalis Rhizoma-Toosendan Fructus were collected from Pharmaceutical Standard of Ministry of Public Health of the People's Republic of China-TCM Formulation and input into TCM inheritance support platform software (V2.5) to establish the database. The frequency of attending diseases, compatibility medicinal materials, and meridian of drug were analyzed statistically. The core combination of medicinal materials in the prescriptions containing Corydalis Rhizoma-Toosendan Fructus were analyzed statistically with association rule Apriori algorithm (support degrees were 10%, 20%, 30%, confidence was 0.90). Meridian of drug with higher compatibility frequency were selected and analyzed in respect of prescription rules. Results: A total of 51 prescriptions containing Corydalis Rhizoma-Toosendan Fructus were screened, eight kinds of attending diseases (frequency≥2), such as stomachache, hypochondriac pain, leukorrhagia, dysmenorrhea, pelvic inflammation, menstrual disorder, etc. Nine kinds of attending syndrome (frequency≥2) were included such as liver-stomach disharmony, syndrome of qi stagnation and blood stasis, syndrome of liver depression and qi stagnation, syndrome of liver depression and blood deficiency, syndrome of blood-heat in uterus, etc. There were 17 commonly used compatibility medicinal materials (frequency≥5), including Paeoniae Radix Alba, Aucklandiae Radix, Glycyrrhizae Radix et Rhizoma, Cyperi Rhizoma etc. There were 20 commonly used medicinal materials combinations (frequency≥6), including Corydalis Rhizoma-Paeoniae Radix Alba-Toosendan Fructus, Corydalis Rhizoma-Aucklandiae Radix-Toosendan Fructus, Corydalis Rhizoma-Glycyrrhizae Radix et Rhizoma-Toosendan Fructus, Corydalis Rhizoma-Cyperi Rhizoma-Toosendan Fructus. Meridian of drug with higher compatibility frequency was distributed to liver, spleen and stomach channel tropism. There were five kinds of core medicinal materials commonly acted on the liver meridian with Corydalis Rhizoma-Toosendan Fructus, including Aucklandiae Radix, Paeoniae Radix Alba, Citri Reticulatae Pericarpium, Amomi Fructus, and Aquilariae Lignum Resinatum. There were commonly used core medicinal materials combinations (frequency≥7), including Corydalis Rhizoma-Aucklandiae Radix-Toosendan Fructus, Corydalis Rhizoma-Paeoniae Radix Alba-Toosendan Fructus, Corydalis Rhizoma-Citri Reticulatae Pericarpium-Toosendan Fructus, Corydalis Rhizoma-Citri Reticulatae Pericarpium-Paeoniae Radix Alba-Aucklandiae Radix-Toosendan Fructus. There were three kinds of core medicinal materials commonly acted on the spleen meridian and the stomach meridian with Corydalis Rhizoma-Toosendan Fructus, including Aquilariae Lignum Resinatum, Aucklandiae Radix and Amomi Fructus. There were commonly used core medicinal materials combinations (frequency≥4), including Corydalis Rhizoma-Aquilariae Lignum Resinatum-Toosendan Fructus, Corydalis Rhizoma-Aucklandiae Radix-Toosendan Fructus, Corydalis Rhizoma-Amomi Fructus-Toosendan Fructus. Conclusions: Herbal medicines used frequently in prescriptions containing Corydalis Rhizoma-Toosendan Fructus can regulate qi flowing for relieving pain. The medicine using is relatively concentrated, and the composition is clear. In addition, Prescription rules of three kinds of meridian prescriptions were chosen to make comparative analysis, and the compatibility features of the prescriptions containing Corydalis Rhizoma-Toosendan Fructus was reflected in different meridian of drug and the composing principles. This study also can provide theoretical basis for treating different diseases with same method and the better application of Corydalis Rhizoma-Toosendan Fructus in clinical practice.

Molecular mechanism of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair against sepsis based on integrative pharmacology platform of traditional Chinese medicine / 中国中药杂志

Guizhi Decoction is a resolving agent,which is a classic prescription for traditional Chinese medicine. It is effective in the treatment of sepsis in clinical practice. However,due to the complexity of the prescription,its anti-sepsis mechanism is difficult to be clarified. The " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair,as the classic compatibility for medicinal and medicinal herbs,is the core of Guizhi Decoction. In this study,Cinnamomi Ramulus-Paeoniae Radix Alba drug pair was used as the research object and the molecular mechanism of its treatment of sepsis was investigated by analyzing the chemical compositions with integrative pharmacology platform( TCMIP,http://www.tcmip.cn/),predicting disease target,analyzing gene function and pathway of " Cinnamomi Ramulus-Paeoniae Radix Alba" in treatment of sepsis,and establishing a multi-dimensional network relationship of " Chinese medicine-chemical components-core targets-key pathways". The prediction results of " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair showed that its anti-sepsis effect was associated with 45 active components,and the active components played an anti-sepsis role through multiple targets and pathways,involving inflammatory targets such as PF4,MyD88,TLR4,BDKRB2,CD14,and NOS3. The sepsis was relieved mainly by regulating Toll like signaling pathway,Fox O signaling pathway,chemokines signaling pathway,thyroid and insulin endocrine signaling pathways and biological processes. This study provides a scientific basis for further development of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair and Guizhi Decoction against sepsis.

Based on cAMP-CREB-BDNF pathway to explore mechanism of antidepressant effect of Bupleuri Radix and Paeoniae Alba Radix drug pair / 中草药

Objective To investigate the antidepressant effect of Bupleuri Radix and Paeoniae Alba Radix drug pair based on the cAMP-CREB-BDNF pathway. Methods The rat depression model was established by CUMS. The contents of cAMP, p-CREB, BDNF, and PDE4 in rat hippocampal and cAMP levels in rat plasma were determined by ELISA. The expression of BDNF mRNA in hippocampus, hypothalamus, and cortex were measured by RT-PCR. Results Compared with the model group, the positive drug group and Bupleuri Radix and Paeoniae Alba Radix drug pair can reverse the cAMP content in the hippocampus and plasma and the decreased contents of CREB and BDNF in the rat hippocampus. At the same time, the positive drug group, Bupleuri Radix, and Paeoniae Alba Radix can increase the expression of BDNF mRNA in hippocampus, cortex, and hypothalamus of rats. Conclusion The Bupleuri Radix and Paeoniae Alba Radix drug pair has obviously antidepressant effect on CUMS rat model, which can achieve antidepressant effect by regulating cAMP-CREB-BDNF pathway.

The influence of the drug pair of Baizhu-Fuzi on the survival time of nude mice which have bone metastasis of breast cancer and the TGF-β1 and PTHrP in their serum / 中成药

AIM To observe the drug pair Baizhu-Fuzi's protection on the breast cancer nude mice with bony metastasis and to explore the mechanism of bone metastasis.METHODS Nude mouse models of breast cancer with bone metastasis were developed through injection of breast cancer cell MDA-MB-231BO into the left ventricle.Nude mice were randomly divided into group A and group B.Group A were subdivided into model group,zoledronic acid group and the drug pair of Baizhu-Fuzi group;and Group B were subdivided into sham-operation group,model group,zoledronic acid group and Baizhu-Fuzi group were subsequently administered with the intervention accordingly.The nude mice in group A had their surviving time and the weight changes observed;and those in group B had the degree of bone metastasis examined.Tartrate resistant acid phosphatase (TRAP) method for quantitative determination of osteoclast in bone metastasis,and ELISA method were employed to check the content of TGF-β1 and PTHrP in serum.RESULTS Compared to the model group,Baizhu-Fuzi group displayed distinctly longer survival time (P ＜ 0.05),reduced rate of weight loss 6 weeks after modeling (P ＜ 0.05),significantly declined degree of bone metastasis (P ＜ 0.01),and significantly decreased quantity of TRAP (+) cell (P ＜ 0.05) and serum TGF-β1 and PTHrP (P ＜ 0.05).CONCLUSION The drug pair,Baizhu-Fuzi's influence in TGFβ signal path control and PTHrP expression reduction may contribute to the weight loss management,prolonged survival time,osteolytic bone defect rectification in mouse models of breast cancer with bone metastasis.

Effects of Taoren-Honghua drug pair on degeneration of cervical disc cartilage endplate in rat model of dynamic and static forces imbalance / 中国药理学通报

Aim To investigate the effect of TaorenHonghua drug pair on intervertebral disc degeneration (IVDD) in rats.Methods Fifty healthy Wistar rats were randomly divided into control group,model group,sham group,meloxicam group and Taoren-Honghua drug pair group,with 10 rats in each group.We established dynamic and static forces imbalance of cervical disc degeneration model or sham surgery in rats.12 weeks later,rats were intragastrically administered with meloxicam,Taoren-Honghua drug pair or saline for 30 days.C4/5 and C6/7 discs were harvested from rats.ABOG staining was used for observation of intervertebral disc morphology,real time PCR for mRNA expressions of type Ⅱ collagen (Col Ⅱ) and type Ⅹ collagen (Col Ⅹ),and immunohistochemical staining for Col Ⅱ and Col Ⅹ.Results Compared with model group,Col Ⅱ expression increased,while Col X expression decreased in chondrocyte of intervertebral disc in Taoren-Honghua-treated group(P ＜ 0.01).Conclusion Taoren-Honghua drug pair could delay the degeneration of cartilage endplate in rat intervertebral disc.

Research Progress on Yueju Pill in the Treatment of Depression and Associated Traditional Chinese Medicine Connotation / 世界科学技术-中医药现代化

Depression has become a serious disease affecting the health of Chinese people. Yueju pill has shown a unique rapid and lasting anti-depression effect, and Yueju pill can rapidly improve Parkinson's disease with depression.The drug pair of Fructus Gardeniae and Rhizoma Ligustici Chuanxiong is necessary for traditional Chinese formula Yueju Pill for antidepressant effect. Recent studies have found the antidepressant effect of Yueju pills at regular doses, and an integrative pharmacological method was adopted to predict the targets and pathways of Yueju pill and explore its molecular mechanism for depression. In recent years, there has been an increasing number of clinical studies on the treatment of depression with Yueju pills and significant therapeutic effects. A new clinical study found that Yueju pill may have antidepressant effects and increase serum BDNF concentration. This paper reviewed the recent research progress of Yueju pill in the treatment of depression in recent 5 years.

Exploration of “principle-recipe-composition-target-activity” association of Bupleuri Radix and Scutellariae Radix drug pair for diabetes treatment based on network pharmacology / 药学学报

By using the integrated pharmacology platform and the big data of traditional Chinese medicine combined with the pharmacology thinking of "principle-recipe-composition-target-pathway-activity" in this study, we predicted the material basis and mechanisms of Bupleuri Radix and Scutellariae Radix drug pair for the treatment of diabetes. Fifty-nine active components were predicted, which included saponins, flavones, essential oil, fatty acids and so on. They acted on twenty-two direct targets and twenty-six main pathways respectively.The known disease targets of diabetes include arginine vasopressin receptor gene (AVP), retinoblastoma (RB1), receptor active modified protein (RAMP), platelet growth factor receptor (PDGFR), insulin receptor (INSR), α-glucosidase (GAA), etc. The pathways with diabetes effect involves endocrine system, circulatory system, digestive system, thyroid hormone signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway, lipid metabolism and other related biological processes and metabolic pathways. The results of virtual screening in molecular docking technology indicate that flavonoids from Bupleuri Radix and Scutellariae Radix drug pair can easily form good docking mode and high affinity with peroxisome proliferators activated receptor γ (PPAR-γ) and glycogen synthase kinase-3β (GSK-3β), showing antidiabetic activity. The study provides information for the treatment of diabetes by Bupleuri Radix and Scutellariae Radix drug pair, and a new thought for the study of drug pair and complex prescription.

Molecular mechanism of Bupleuri Radix and Scutellariae Radix drug pair for depression based on integrative pharmacology platform of traditional Chinese medicine / 中国中药杂志

Xiaochaihu decoction is a classic prescription of traditional Chinese medicine. Modern research has proved its anti-depression effect. However, its pharmacological mechanism for anti-depression effect is difficult to be unveiled because of the complexity of compound Chinese medicines. Bupleuri Radix and Scutellariae Radix is the core drug pair of Xiaochaihu decoction. In this research, Bupleuri Radix and Scutellariae Radix were analyzed by the integrative pharmacology platform to study its molecular mechanism for anti-depression. One hundred and sixteen active ingredients were predicted, 62 for Bupleuri Radix, mainly including saikosaponins, acids, alcohols, and 54 for Scutellariae Radix, mainly including flavonoids and glycosides. Its anti-depression effect was relevant to 118 core targets, including 22 known disease targets, such as serotonin receptor(HTR2C), activating transcription factor(ATF1, ATF2), δ opioid receptor(OPRD1), μ opioid receptor (OPRM1), κ opioid receptor(OPRK1), inositol monophosphatase(IMPA1), Toll-like receptor 4 (TLR4), histamine H1 receptor(HRH1), neurotrophic factor tyrosine kinase receptor1 (NTRK1), Glycogen synthetase kinase 3β(GSK3β), etc. The antidepressant effect involved positive regulation of transcription from RNA polymerase Ⅱ promoter, transcription factor binding, cytosol, transcriptional regulation of DNA template, enzyme binding, endocrine system, nervous system, neurotrophin signaling pathway, cell growth and death, signal transduction, thyroid hormone signaling pathway and other related biological processes and metabolic pathways. This study provides a scientific evidence for further study of the anti-depression mechanism of this drug pair.

Rules for compatibility in traditional Chinese medicine prescriptions / 中华医学图书情报杂志

The association rules in data of traditional Chinese medicine prescriptions were analyzed using SQL Server 2008,which showed that 17 core compatible drug pairs were in line with the association rules.For example,platycodon grandiflorum combined with liquorice,known as Liquorice and Platycodon Decoction,can treat the principal and secondary aspects of a disease by ventilating the lungs and resolving the phlegm,removing the toxic substances and relieving the sore throat.Mining compatible drug pairs by analyzing their association rules can provide evidence for their clinical application.

Effect of Drug Pair of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi on TLR4/MyD88 Signal Transduction Pathway of Rats with Acute Gouty Arthritis / 广州中医药大学学报

Objective To observe the effects of the drug pair of Rhizoma Polygoni Cuspidati ( Huzhang) and Ramulus Cinnamomi ( Guizhi) on the Toll-like receptor 4 mediated myeloid differentiation factor 88 ( TLRs/MyD88) signaling pathway of rats with acute gouty arthritis induced by monosodium sodium urate (MSU) , so as to explore its therapeutic mechanism. Methods Forty-eight male SD rats were divided into normal group, modele group, blank plasmid group, positive plasmid group, Huzhang- Guizhi herb-pair (7 g/kg) group, and Huzhang-Guizhi herb-pair ( 7 g/kg) siRNA group, 8 rats in each group. The normal group, plasmid groups and model group were given physiological saline, and the left groups were given the corresponding drug by intragastric administration for 10 continuous days ( once daily ) . On the seventh day of intragastric gavage, acute gouty arthritis were induced by injection of MSU into the rat ankle joint, and normal group was injected with the samevolume of normal saline. Positive plasmid group and Huzhang-Guizhi herb-pair siRNA group were injected with the constructed siRNA-TLR4 plasmid targeting TLR4 gene ( TLR4-siRNA) to inhibit the in-vivo TLR4 gene expression. Pathological changes of the synovial tissues were detected, the contents of peripheral blood tumor necrosis factor alpha ( TNF-α) and interleukin 1 beta ( IL-1β) were detected by double antibody sandwich method, and the mRNA and protein expression levels of TLR4, MyD88, TNF receptor-associated factor 6 ( TRAF-6) in peripheral blood mononuclear cells of rats were detected by real-time fluorescence quantitative polymerase chain reaction ( PCR) and Western blot methods. The nuclear factor kappa B ( NF-κB) p65 immunoactivity was assayed by immunohistochemistry. Results Compared with the normal group, the model group had obvious hyperplasia of synovial cells and the inflammatory cell infiltration ( dominated by lymphcytes and monocytes) , and had amount of cellulose adhesive on the synovial membrane surface. Compared to the model group, positive plasmid group, Huzhang- Guizhi herb-pair group and Huzhang-Guizhi herb-pair siRNA group could obviously relieve the inflammatory cell infiltration, and improve synovial cell proliferation reaction. Compared to the normal group, serum levels of TNF-α and IL-1β, and the expression levels of TLR4, MyD88, TRAF-6 mRNA and protein in the peripheral blood mononuclear cells as well as the synovial NF-κB p65 ex pression in the model group were significantly increased ( P<0.01). Compared to the model group, positive plasmid group, Huzhang-Guizhi herb-pair group and Huzhang- Guizhi herb-pair siRNA group showed significant decrease in the levels of TNF-α, IL-1β, TLR4 MyD88, TRAF-6 and NF-κB p65 ( P<0.05 or P<0.01) . Conclusion Huzhang-Guizhi herb-pair can regulate the cytokines of the synovial membrane tissue in acute gouty arthritis rats, which may be related with its effect on inhibiting abnormal activation of TLR4-MyD88-NF-κB pathway in synovial tissue.

Zhou Enchao' s Experience in Treating Diabetic Nephropathy / 浙江中医药大学学报

Objective]The article summarizes the experience of professor Zhou Enchao in treating diabetic nephropathy . [Methods]Pro.Zhou Enchao treats diabetic nephropathy by pairing drugs; discuses the clinical experience of professor Zhou Enchao in the treatment on diabetic nephropathy from the pathogenesis,treatment,and one case. [Results]Professor Zhou Enchao believes that the disease is caused by Qiyin deficiency, mixed with wet ,Fengxie and blood stasis. Pro.Zhou Enchao treats diabetic nephropathy by pairing drugs,such as astragalus membranaceus and Chinese yam,radix rehmanniae recene and radix scrophulariae,corn stigma and loofah sponge,stiff silkworm and scorpio,salvia miltiorrhiza and earthworm. And these usually lead to good curative effect. [Conclusion]Professor Zhou's clinical experience in treating diabetic nephropathy from pairing drugs is well worth extending in clinic for it always has significant effect.

Optimization of ethanol extraction process of Psoraleae Fructus-Myristicae Semen drug pair by orthogonal test combined with fingerprint / 中草药

Objective: To optimize the ethanol extraction process of Psoraleae Fructus-Myristicae Semen (psoralen-nutmeg) drug pair. Methods: Using L9(34) orthogonal design, the effects of ethanol concentration, ethanol amount, extraction time, and extraction times on the extraction process were investigated. The contents of psoralen, isopsoralen, and dehydrodiisoeugenol, dry extract yield, and total area of HPLC fingerprint characteristic peaks were used as comprehensive evaluation indexes. Results: The optimum process conditions were as follows: 50% ethanol, six times of the ethanol volume, extracted for three times, each time for 2 h. Conclusion: The method provides the basis for the determination of ethanol extraction process of Psoraleae Fructus-Myristicae Semen drug pair.

Study on Drug Pair of Cassia Twig and White Peony Root by HPLC/MS Analysis Based on Theory of“Xin-Gan Hua-Yang and Suan-Gan Hua-Yin” / 世界科学技术-中医药现代化

This article was aimed to study the different clinical characteristics using drug pair of Cassia twig and white peony root with the contents ratio of 1:1 and 1:2. Based on the different clinical treatment of drug pair of Cas-sia twig and white peony root, different compositional ingredients in ratio of 1:1 and 1:2 were illuminated by HPLC/MS method. The drug pair of Cassia twig and white peony roots in ratio of 1:1 and 1:2 and single herbs were ex-tracted for HPLC/MS analysis. A protocol was followed, including acetonitrile - 0.1% acetic acid with gradient elution, positive mode, 350℃ capillary temperature and 300℃ vaporization temperature. The results showed that Procyanidol B2 and 2-Hydroxy cinnamal dehyde can be extracted from single Cassia twig, but 2-Hydroxy cinna-mal dehyde cannot be detected in drug pair. It showed the contents of Procyanidol B2 in 1:1 ratio was more than 1:2 ratio. Simultaneously, Palbinone, paeoniflorin sulfonate, 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Pae-oniflorin isomers, Benzoylpaeo-niflorin, and Benzoyl Paeoniflorin isomers can also be dissolved in white peony root. In addition, the contents of 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Benzoylpaeo-niflorin, and Benzoyl Paeoniflorin isomers in 1:1 were more than 1:2. The contents of Palbinone, paeoniflorin sulfonate and Paeoniflorin isomers in 1:2 were more than 1:1. It was concluded that Procyanidol B2, 1,2,3,6-Tetra-O-galloyl-β-D-glucose, Paeoniflorin, Benzoylpaeo-niflorin and Benzoyl Paeoniflorin isomers in 1:1 were more than 1:2. The contents of Pal-binone, Paeoniflorin sulfonate and Paeoniflorin isomers in 1:2 were more than 1:1. It provided a scientific basis for traditional Chinese medicine treatment using rational drug pair.

Effects of compatible herbs and pH value conditions on change rule of anthraquinones in Rhei Radix et Rhizoma / 中草药

Objective: To study the effects of various compatible herbs and pH value conditions on the change rule of anthraquinones in Rhei Radix et Rhizoma (RRR). Methods: The pH value of the extracted solution from seven compatible herbs[vinegar Kansui Radix (vKR), Moutan Cortex (MC), Scutellariae Radix (SR), Coptidis Rhizoma (CR), Aconiti Lateralis Radix Praeparata (ALRP), Aurantii Fructus Immaturus (AFI), and Magnoliae Officinalis Cortex (MOC)] were determined, then RRR was added into hydrochloric acid solution with the same pH value as the above solutions and boiled, in which the contents of anthraquinones were determined by UV-Vis and HPLC. The contents of anthraquinones were compared with those in the decoction of compatible herbs and single RRR. Results: The results of UV-Vis showed that total anthraquinones got the lowest amount when RRR and CR were boiled together while the highest appeared when RRR and SR were boiled together; the contents of total anthraquinones were increased when the pH value was increased. The results of HPLC showed that the five anthraquinones got the lowest dissolving-out quantity when RRR and CR were boiled together while the highest appeared when RRR and ALRP were boiled together. Under the conditions of different pH values, the highest dissolving-out quantity was got when the pH value reached 5.6. Conclusion: Both the compatible herbs and pH value could affect the dissolution of anthraquinones during the extraction. However, the effects of various compatible herbs and different pH value conditions adjusted by hydrochloric acid are different, and the pH value conditions have greater effects.

Study on Chemical Constituents of Volatile Oils in Drug Pair of Flos Lonicerae and Fructus Forsythiae by GC-MS / 中药新药与临床药理

Objective To discuss the influence of drug compatibility on the components of the volatile oil in Flos Lonicerae and Fructus Forsythiae. Methods GC-MS system was used to analyze the volatile oil in Flos Lonicerae, Fructas Forsythiae and their combination. The effect of compatibility on the components and content of volatile oil was evaluated. Results The results of GC-MS showed that gerani]o, tetradecanoic acid methyl ester, hexadecanoic acid ethyl ester, fluoranthene, 9, 12, 15-Octadeeatrienoic acid ethyl ester and linoleic acid was detectable in Flos Lonicerae but was undetectable in the drug pair; camphene, alpha-terpinene, perillaalcohol, 2-beta-pinene, beta-hexadecanal, phellandrene was de-tectable in Fructus Forsythiae but was undetectable in the drug pair; limonene, isolongifolene, nonadecane was detectable in the drug pair but was undetectable in the two single drugs. Conclusion The compatibility of the drug pair has an effect on components and contents in the volatile oil of Flos Lonicerae and Fructus Forsythiae.