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Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.
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Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).
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ObjectiveTo predict the possible quality markers (Q-markers) of Arisaema Cum Bile in the prevention and treatment of stroke based on ultra performance liquid chromatography-quadrupole-time-of-flight tandem mass spetrometry (UPLC-QTOF-MS/MS) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP) v2.0. MethodUPLC-QTOF-MS/MS was employed with the mobile phase of 0.1% formic acid aqueous solution (A)-0.1% formic acid acetonitrile solution (B) for gradient elution (0-3 min, 0.2%-5%B; 3-5 min, 5%-8%B; 5-8 min, 8%-10%B; 8-14 min, 10%-25%B; 14-18 min, 25%-50%B; 18-20 min, 50%-70%B; 20-21 min, 70%-98%B; 21-23 min, 98%B; 23-24 min, 98%-0.2%B; 24-26 min, 0.2%B), the flow rate of 0.5 mL·min-1 and electrospray ionization (ESI). High quality MS/MS data were scanned in positive and negative ion modes with scanning range of m/z 50-1 500. A local database of the chemical constituents in Arisaema Cum Bile was established by UNIFI 1.8. Then the chemical constituents in Arisaema Cum Bile were characterized by matching with the local database and comparing with the reference substances and literature information. TCMIP v2.0 was used to obtain the targets corresponding to the identified components of Arisaema Cum Bile and stroke, and the "disease-formula" correlation analysis was carried out to screen the core targets by topological eigenvalues. DAVID 6.8 was used for enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of core targets. According to the "five principles" of Q-markers and combined with literature reports, the Q-markers of Arisaema Cum Bile in the prevention and treatment of stroke were predicted, and the core components acting on these target genes were obtained. Cytoscape 3.8.0 was employed to draw the network diagram of "medicinal materials-active ingredients-target genes-pathways". Finally, AutoDock Vina 1.2.2 was used to calculate and verify the molecular docking between the candidate components and the key targets. ResultA total of 76 chemical components was identified in positive and negative ion modes, 85 core targets were collected for Arisaema Cum Bile in the prevention and treatment of stroke. A total of 31 stroke-related pathways, 23 target genes and 9 main active components of Arisaema Cum Bile acting on these genes were screened, and then we determined 4 possible Q-markers for Arisaema Cum Bile in the prevention and treatment of stroke according to the "five principles". ConclusionThe possible Q-markers of Arisaema Cum Bile for stroke are gallic acid, apigenin-6,8-di-C-glucoside, apigenin and cholic acid, and the target of these four components may be estrogen receptor alpha (ESR1).
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Chinese medicine injections(CMIs) have higher requirements for quality consistency and controllability than other traditional Chinese medicine products. The implementation of Good Agricultural Practice of Medicinal Plants and Animals(GAP) is an important factor that guarantees the quality stability of raw Chinese medicinal materials and affects the quality of CMIs. Through literature review, data research, expert consultation, and statistical analysis, this paper analyzes the current status of GAP management of key CMIs and the impact of GAP management of raw medicinal materials on the quality consistency and controllability of CMIs. Furthermore, it demonstrates the rationality, necessity, and feasibility of the full implementation of GAP on the basis of CMIs safety re-evaluation.
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Drugs, Chinese Herbal , Injections , Medicine, Chinese Traditional , Plants, MedicinalABSTRACT
Good agricultural practices(GAP) for Chinese herbal medicine(CHM) is the source of quality control in the production of CHM. To ensure the safety, efficacy, and quality of Chinese herbal and natural medicine, the international community has been exploring the implementation of GAP for CHM. The implementation of GAP for CHM has a far-reaching impact, and the scale planting of CHM has been expanding. However, the medicinal materials produced by the GAP bases for CHM still cannot fully meet the market demand, and the output and quality of CHM remain to be improved. This paper summarizes construction status of GAP bases for CHM.The 129 companies that passed the certification during the implementation of GAP for CHM included 196 GAP bases, forming the scale CHM production zone with Sichuan province, Yunnan province, Jilin province, Henan province, and Shandong province as the core.The total area of GAP bases for CHM in China is about 250 000-500 000 Mu(1 Mu≈667 m2), which is still less than 1% of the total production area of CHM. The international agricultural production quality management strategies are all market-oriented behaviors.Drawing on the international good agricultural and collection practice(GACP) and hazard analysis critical control point(HACCP) as well as the relevant policies of Chinese quality management of CHM, we put forward feasible suggestions for the further implementation of GAP for CHM:(1)The market rules and international experience should be followed and employed to promote GAP management of CHM and third-party implementation of GAP certification;(2)The sound development of GAP for CHM should be boosted with the HACCP management system and the revision of GAP for CHM;(3)The implementation of policies and standards should be stepped up to facilitate the building of a whole-course traceability system for the production of CHM with high quality and reasonable prices.
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Humans , China , Drugs, Chinese Herbal , Hazard Analysis and Critical Control Points , Medicine, Chinese Traditional , Quality ControlABSTRACT
Objective:To explore active components and mechanism of Dipsaci Radix in treating rheumatoid arthritis (RA) based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP). Method:UPLC-QTOF-MS/MS with electrospray ionization (ESI) was used to qualitatively analyze the chemical components in methanol extract of Dipsaci Radix under positive and negative ion scanning modes. The mobile phase consisted of 0.1% formic acid aqueous solution (A)-acetonitrile (B) for gradient elution (0-10 min, 0.2%-20%B; 10-20 min, 20%-40%B; 20-25 min, 40%-50%B; 25-33 min, 50%-98%B; 33-35 min, 98%-0.2%B), and the scanning range was <italic>m</italic>/<italic>z</italic> 50-2 000. Based on TCMIP, candidate target groups of Dipsaci Radix, RA and syndrome with Yin deficiency of liver and kidney were obtained, and correlation analysis on "disease-syndrome-prescription" was used to enrich the main active components and key targets. Cytoscape 3.8.0 and STRING 11.0 database were used to construct protein-protein interaction (PPI) network diagram. Metascape platform was used to analysis gene ontology biological progress and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. Result:A total of 81 ingredients were identified by UPLC-QTOF-MS/MS. Based on TCMIP, 283 candidate targets corresponding to 81 ingredients, 7 RA related targets and 215 genes corresponding to syndrome with Yin deficiency of liver and kidney were collected. With further correlation analysis on "disease-syndrome-prescription", 17 key active ingredients were predicted, mainly including saponins and fatty acids of Dipsaci Radix. It mainly involved 7 hub targets, namely tumor necrosis factor (TNF), nuclear factor-<italic>κ</italic>B subunit 1 (NF-<italic>κ</italic>B<sub>1</sub>), hepatocyte nuclear factor 4 alpha (HNF4A), nuclear receptor subfamily 3 group C member 1 (NR3C1), peroxisome proliferator activated receptor gamma (PPARG), nuclear receptor subfamily 1 group H member 4 (NR1H4) and nuclear receptor coactivator 1 (NCOA1). All of them were related to inflammation, and two of them were related to bile acid pathway. The 7 hub targets and 7 pathways played an important role in RA were screen out, including 4 bile acid related pathways and 3 inflammatory related pathways. Conclusion:UPLC-QTOF-MS/MS combined with TCMIP preliminarily elucidates the regulatory effect of multi-components in Dipsaci Radix on several pathways related to the inflammatory response and bile acid synthesis and metabolism, which lays a foundation for further study on the mechanism of Dipsaci Radix against RA.
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This study aims to explore the efficacy of Chinese medicine injections( CMIs) for promoting blood circulation and removing blood stasis for acute cerebral infarction from the perspectives of clinical medication and mechanism of action based on two complex network analysis methods. Firstly,the current 13 kinds of CMIs for acute cerebral infarction were obtained from 2019 List of medicines for national basic medical insurance,industrial injury insurance and maternity insurance with the method of network Meta-analysis. Secondly,with the use of network pharmacology,the mechanisms of top 2 CMIs with the highest therapeutic effect for acute cerebral infarction were explored from two levels including core target and network function enrichment. The result of network Meta-analysis showed Mailuoning Injection was superior to Danhong Injection in terms of total effectiveness rate for neurological deficit score and NIHSS score. The network pharmacology results showed that Mailuoning Injection had more core targets,interaction networks,enriched biological functions and more signaling pathways than Danhong Injection for cerebral infarction. Both two CMIs can play a role in treating cerebral infarction through core targets such as TP53 and NOS3,biological processes such as fibrinolysis,nitric oxide biosynthesis,nitric oxide-mediated signal transduction,negative regulation of apoptosis in endothelial cells and apoptosis process,as well as the signaling pathways such as PI3 K-Akt signaling pathway,HIF-1 signaling pathway and cell apoptosis signaling pathways. The results of pharmacological studies explained their differences in clinical efficacy to a certain extent. A research strategy based on curative effect should be advocated in efficacy evaluation of traditional Chinese medicine,where comparative research on clinical efficacy can be conducted firstly,and then mechanism research based on outstanding effective drugs to better provide references and basis for selection of similar competitive drugs for one disease in the clinical practice.
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Female , Humans , Pregnancy , Cerebral Infarction/drug therapy , Drugs, Chinese Herbal/therapeutic use , Endothelial Cells , Injections , Medicine, Chinese Traditional , Signal TransductionABSTRACT
Objective:A new prescription containing Portulacae Herba was created and the molecular mechanism of the new prescription for treating diabetes was clarified based on big data of traditional Chinese medicine (TCM). Method:Taking Portulacae Herba as the key word, the TCM Inheritance Support System and Encyclopedia of TCM (ETCM) were used to excavate the most frequently used medicines combined with Portulacae Herba, and form a new prescription. Based on the basic theory of TCM, this paper analyzed the rationality of the new prescription in treating diabetes, and used the Integrative Pharmacology-based Research Platform of TCM (TCMIP) to predict the target of the new prescription, and constructed the interaction network between drugs and targets of diabetes-related diseases, the key targets of drug intervention were enriched and analyzed, and the network graph of TCM-chemical composition-key target-pathway was drawn. Result:There were 89 prescriptions containing Portulacae Herba in ETCM. The most frequently used medicines in combination with Portulacae Herba were Phellodendri Chinensis Cortex, Rehmanniae Radix and Saposhnikoviae Radix, the four medicines were combined into a new prescription. According to the new prescription to treat diabetes, 89 key core target information was obtained, among which there were 10 targets of drug and disease, including phosphoinositide-3 kinase regulatory subunit 1 (PIK3R1), insulin (INS), glucokinase (GCK), etc. The new prescription treated diabetes by regulating growth hormone receptor signaling, protein kinase A (PKA) activation, adrenoceptors and other pathways. Conclusion:The therapeutic effect of new prescription containing Portulacae Herba created by big data analysis of TCM on diabetes reflects multi-component, multi-target, multi-pathway characteristics of TCM, which can provide scientific basis for explaining the mechanism and material basis of this new prescription in the treatment of diabetes.
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Objective:To predict the potential molecular mechanism of Yangxue Antai Fang in treating prethrombolic state of recurrent spontaneous abortion (RSA-PTS). Method:The chemical constituents and drug targets of Yangxue Antai Fang were collected by Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP V2.0). RSA-PTS disease target information was collected by TCMIP V2.0 and improved by Online Mendelian Inheritance in Man (OMIM) database. The interaction of these targets was analyzed and key target network was constructed. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were further performed. Finally, Cytoscape 3.5.1 was used to build up a multidimensional network of TCM-ingredient-target-pathway. The levels of absorption, distribution, metabolism, excretion and toxicity (ADMET) of the main components in the network were analyzed. Result:A total of 310 chemical constituents and 975 targets were collected from 8 TCMs in Yangxue Antai Fang. A total of 143 targets of RSA-PTS were obtained. A total of 243 core targets were obtained by the interrelationship analysis of drug and disease targets. The analysis of the top 100 core targets showed that these targets might participate in treating RSA-PTS by affecting biological processes related to thrombosis, such as blood coagulation, platelet activation, positive regulation of angiogenesis and so on. Pathway analysis showed that these targets were mainly concentrated in complement and coagulation cascades, platelet activation, estrogen signaling pathway, thyroid hormone signaling pathway, etc. Multidimensional network analysis in combination with ADMET level showed that 14 components (leonurine, paeonol, vanillin, and so on) may play a therapeutic role in RSA-PTS by affecting coagulation factors Ⅱ (F2), plasminogen (PLG) and estrogen receptor 1 (ESR1) proteins involved in complement and coagulation cascades, platelet activation, thyroid hormone signaling pathway and others. Conclusion:The main chemical constituents in Yangxue Antai Fang may improve RSA-PTS by regulating complement and coagulation cascades, blood coagulation, platelet activation and other biological processes.
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The prevalence and mortality of cardiovascular diseases are still on the rise in China. Percutaneous coronary intervention(PCI)is the most effective strategy to reduce coronary artery stenosis and occlusion, it can also improve clinical symptoms on patients with coronary heart disease. Clinically, a large number of patients still have heartache symptoms after recanalization of the great vessel. During the perioperative period, PCI is often accompanied with adverse events such as oxidative stress, inflammation, calcium overload, endothelial function damage, and thrombus obstruction. More specifically, during the process of PCI, oxidative stress is more severe than other damages. For example, during the reperfusion period of PCI, the outbreak of reactive oxygen species (ROS) can lead to abnormal mitochondrial energy transfer and cell ion homeostasis, resulting in endothelial cell injury, it can also increase the level of vascular permeability, albumin leakage, the adhesion of leukocyte and platelet, and the level of vascular stenosis. After PCI, traditional Chinese medicine(TCM) brings vasucular restenosis into the category of " palpitation" . The movement of Qi and bloods is tightly related to the five Zang-orans. When the movement of Qi and blood is stagnant, the function of the heart's blood production and circulation is blocked, resulting in Qi of deficiency and blood stasis, thus causing a state of physical weakness. Moreover, at present, Probucol and Ticagrelor and other first-line clinical drugs have certain limitations, and ignore the body' s current status of " essential illusory and real" , unable to coordinate the relationship between the body' s Qi and blood, Yin, Yang and five zang-organs. The purpose of this research is to perform the negative effects of oxidative stress on coronary artery based on the molecular research of modern medicine accompanied with acknowledgement of TCM and to conclude the process of researching prevention and treatment of TCM, and to provide reference for the treatment of coronary artery and coronary artery experimental study.
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At present, most of Chinese patent medicines have problems, such as weak scientific basis, unclear clinical value evaluation, etc., which lead to the lack of sufficient evidence for the entry into the essential medicine list, medical insurance catalog and other important health resource allocation tools. This has a negative impact on the development of traditional Chinese medicine. It is urgent to establish a comprehensive evaluation methodology system of Chinese patent medicine in China. There are at least three reasons including producing evidence for clinical rational use scientifically, developing an objective and transparent selecting strategy, eventuating and highlighting its clinical value. The process and method of health technology assessment(HTA) can provide reference for the establishment of comprehensive evaluation method of Chinese patent medicine. However, HTA is rarely carried out in the field of traditional Chinese medicine. The latest domestic and international research showed that HTA combined with multi-criteria decision analysis(MCDA) can increase the transparency of decision-making and improve the quality of decision-making. The combined two formed the EVIDEM framework, which is conducive to drug selection and its clinical use. In this paper, the EVIDEM framework was introduced to establish the methodology framework of the comprehensive clinical evaluation system of Chinese patent medicine. A preliminary research idea has been put forward. In the future, we can establish a set of comprehensive clinical evaluation methods for Chinese patent medicine in cooperation with relevant national drug decision-making departments and management departments. It is believed that such cooperation could promote the full implementation of the re-evaluation for Chinese patent medicine.
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China , Drugs, Essential , Medicine, Chinese Traditional , Nonprescription Drugs , Technology Assessment, BiomedicalABSTRACT
In this research, high-throughput sequencing was used to investigate the mechanism of Naoxintong Capsules(NXTC) in prevention of post-ischemic inflammation. First, microglia BV-2 inflammatory model was induced by 1.0 μg·mL~(-1) LPS to investigate the effect of intestinal absorption solution of NXTC(NXTCIA) at different concentrations(62.5, 31.25, 15.63, 7.81 μg·mL~(-1)) on LPS-induced BV-2 inflammatory factors in microglia. Then, an RNA-Seq high-throughput sequencing method was performed to identify the differentially expressed mRNAs in microglia BV-2 after pre-treatment with NXTC. GO and KEGG enrichment analysis was used to screen the potential biological processes and related signaling pathways of NXTC in inhibiting inflammation. The results showed that four NXTCIA concentrations could significantly inhibit the release of LPS-induced inflammatory mediators in BV-2 in a dose-dependent manner. Furthermore, high-throughput sequencing results showed that 392 mRNA transcripts were reversed following pre-treatment with NXTC. GO enrichment analysis showed that the transcripts reversed by NXTC were mainly involved in Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway. Taken together, our findings showed that NXTC treatment could provide protective effects against inflammatory response and the mechanism might be related to the regulation of Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway.
Subject(s)
Animals , Mice , Capsules , Drugs, Chinese Herbal/therapeutic use , Inflammation/prevention & control , Ischemia/complications , Lipopolysaccharides , Microglia/metabolism , RNA-Seq , TranscriptomeABSTRACT
The paper analyzed the combined administration of traditional Chinese medicine Shuguan Granules, and studied its six plant herbs, namely Polygoni Multiflori Radix, Salviae Miltiorrhizae Radix et Rhizoma, Polygonati Rhizoma, Chuanxiong Rhizoma, Epomedii Folium, and Carthami Flos by network pharmacology analysis, in order to define chemical constituents and drugs targets through integrated pharmacology platform. Based on the results, indications of Shuguan Granules were collected through the ETCM database. Therefore, the present study could determine the potential optimal indications of the drug. The results showed that chest apoplexy was the main traditional Chinese medicine(TCM) symptom treated by Shuguan Granules, whose monarch drug was Salviae Miltiorrhizae Radix et Rhizoma. Network pharmacology analysis found that the target enrichment results of Shuguan Granules were related to the indications of coronary heart disease, angina and atherosclerosis. According to the indications, angina may be the best indication for Shuguan Granules. The 229 components in Shuguan Granules involved a total of 109 core targets, of which TNF and MMP9 were the direct targets to the angina disease. In addition, Shuguan Granules could also indirectly intervene in the progression of angina through MAPK, NFKB, GF and other targets. The main pathways involving angina pectoris are PI3 K-Akt signaling pathway, RAS signaling pathway, TNF signaling pathway, Estrogen signaling pathway and glycolysis/gluconeogenesis, which can intervene in many aspects of angina, such as inflammatory reaction, blood lipid metabolism and vasodilation.
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Humans , Angina Pectoris , Drug Therapy , Drugs, Chinese Herbal , Therapeutic Uses , Medicine, Chinese Traditional , Signal TransductionABSTRACT
Quality marker(Q-marker) is a new concept and pattern for quality control of traditional Chinese medicine(TCM),which will lead the development direction for quality control of TCM.Among them,how to characterize the overall quality attribute of TCM and its biological effect,is a critical scientific problem in the study of Q-marker.In this paper,integrated pharmacology is utilized to screen out and confirm the Q-marker from the complex system of TCM,so as to solve the critical scientific problem.System biology in vivo is firstly applied to establish the correlation of chemical fingerprints of TCM,their metabolic fingerprints,network targets,biological effects and efficacy of TCM,which is used to preliminary screen out Q-marker of TCM.Following that,a pharmacological method in vitro,including intestinal absorption in vitro coupled with bioactivity assessment,is employed to simultaneously determine the absorbed doses of TCM and evaluate their biological activity.Furthermore,data mining is utilized to establish the exact quantitative mathematic model between Q-marker of TCM and bioactivity.Meanwhile,two representative examples,including Yuanhu Zhitong tablets,Xinsuning capsules,are introduced to identify Q-marker of TCM and establish their quality standards related with bioactivity,which will be beneficial to improve the level of quality control of TCM and ensure the effectiveness and safety of clinical applications.
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By using the traditional Chinese medicine inheritance support system (TCMISS) in this study, the prescription rules of Baizhi formulae were analyzed and the core herbal pair "Baizhi-Chuanxiong" was obtained. Through the systemic analysis of prescription rules of "Baizhi-Chuanxiong" and combined with the pharmacology thinking of "Baizhi-Chuanxiong" in treating headache, the paper was aimed to find out the combination rules containing Baizhi andits molecular mechanisms for treating headaches, and provide the theory basis for further research and reference of Baizhi and its formula. Totally 3 887 prescriptions were included in this study, involving 2 534 Chinese herbs. With a support degree of 20% in analysis, 16 most commonly used drug combinations were screened, which were mainly used to treat 15 types of diseases. Baizhi was often used to treat headache, and the core combination "Baizhi-Chuanxiong" was also often used to treat, consistent with ancient record. A chemical database was established; then the headache and migraine disease targets were retrieved and added in the database to build up the "compounds-targets-pathways "core network of "Baizhi-Chuanxiong" by the internet-based computation platform for IP of TCM (TCM-IP). TCM-IP was then applied to study the molecular mechanism of "Baizhi-Chuanxiong" treatment of headache. The results suggested that37 chemical compounds in the core combination "Baizhi-Chuanxiong" were closely related with headache treatment by adjusting serotonin levels or applying to inflammation-related targets and energy metabolism pathways such as purine metabolism, pyruvate metabolism, fatty acid degradation, carbon metabolism and gluconeogenesis.
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Integrative pharmacology (IP) is a discipline that studies the interaction, integration and principle of action of multiple components with the body, emphasizing the integrations of multi-level and multi-link, such as "whole and part", " and ", " process and activity evaluation". After four years of development and practice, the theory and method of IP has received extensive attention and application.In order to better promote the development of IP, this paper systematically reviews the concepts, research contents, research methods and application fields about IP.
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Shengmaiyin is widely used in the treatment of arrhythmia and has achieved a good effect. Due to the complexity of traditional Chinese medical formula, the pharmacological mechanism of Shengmaiyin in the treatment of arrhythmia is unclear. In this study, we used the internet-based Computation Platform (www.tcmip.cn) to explore the molecular mechanism. Shengmaiyin was found to treat the arrhythmia by modulating the pathway related to energy metabolism such as carbon metabolism, purine metabolism, carbohydrate metabolism, or by regulating the level of ATP. In this study, we find that the main active drug component in Shengmaiyin may be ginseng.
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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.
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AIM To investigate the effects of imperatorin and isoimperatorin on the expression of mouse liver cytochrome P450s and hepatic toxicity in mice.METHODS C57BL/6 mice were randomly divided into control and administration groups,which were treated with imperatorin or isoimperatorin by intragastric administration for two weeks.The effects of two compounds on mRNA expressions of major P450s isoforms were analyzed by RT-PCR.The P450 expression was determined by Western blot.The serum levels of glutamicpyruvic transaminase (GPT),glutamic-oxalacetic transaminase (GOT) and blood total bilirubin (TBIL) were detected by kits.The change of liver tissue was observed with HE staining.RESULTS The Cyp1a2 mRNA expression was significantly induced by 40 mg/kg imperatorin as compared with the control group.For isoimperatorin,the Cyp2c37 mRNA expression was significantly induced.Western blot results showed that CYP1 A2 expression was significantly induced by imperatorin.For isoimperatorin,the CYP2C and CYP2E1 expressions were significantly induced.Blood biochemical indices showed that 40 mg/kg isoimperatorin led to increased serum GOT and TBIL levels.Pathological analysis showed that both compounds (at the doses of 20 mg/kg and 40 mg/kg) could cause liver edema to a certain degree.CONCLUSION Imperatorin is the inducer of CYP1A2,while isoimperatorin is the inducer of CYP2C and CYP2E1.These two compounds (at the doses of 20 mg/kg and 40 mg/kg) can lead to damage for mouse liver.The toxicity of isoimperatorin is stronger than that of imperatorin.
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Cytokines can be divided into two types: proinflammatory cytokines and anti-inflammatory cytokines. Proinflammatory cytokines are a kind of small molecular peptides synthesized and excreted by immune and non-immune cells, which can regulate a variety of physiological functions and play an important role in the process of trauma, pain and infection. Proinflammatory cytokines include TNF, IL-1, IL-6 and IL-8. More and more evidences suggest that proinflammatory cytokines(PICs), such as interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α), are induced in the spinal cord(SC) and dorsal root ganglion (DRG) under various injury conditions, and contribute to pain hypersensitivity. In recent years, with the deepening of studies on neuropathic pain mechanism and the increasing expansion of the neuroinflammation study field, the action mechanisms of cytokines and molecules in regulating cytokines in neuropathic pain are expected to provide new targets for the development of analgesic drugs. This review aims to provide an overview of inflammatory mechanisms for proinflammatory cytokines TNF-α, IL-1β, IL-6, with a focus on neuropathic pain.