Objective To explore the medication rules of traditional Chinese medicine(TCM)and mechanism of action of hub herb pairs for treating insomnia.Methods Totally 104 prescriptions were statistically analyzed.The associati...Objective To explore the medication rules of traditional Chinese medicine(TCM)and mechanism of action of hub herb pairs for treating insomnia.Methods Totally 104 prescriptions were statistically analyzed.The association rule algorithm was applied to mine the hub herb pairs.Network pharmacology was utilized to analyze the mechanism of the hub herb pairs,while molecular docking was applied to simulate the interaction between receptors and herb molecules,thereby predicting their binding affinities.Results The most frequently used herbs in TCM prescriptions for treating insomnia included Semen Ziziphi Spinosae,Radix Glycyrrhizae,Radix et Rhizoma Ginseng,and Poria cum Radix Pini.Among them,the most commonly used were the supplementing herbs,followed by heat-clearing,mind-calming,and exterior-releasing ones,with their properties of warm and cold,flavors of sweet,Pungent,and bitter,and meridian tropisms of liver,lungs,spleen,kidneys,heart,and stomach.The hub herb pairs based on the association rules included Radix Astragali-Radix et Rhizoma Ginseng,Rhizoma Chuanxiong-Radix Glycyrrhizae,Seman Platycladi-Semen Ziziphi Spinosae,Pericarpium Citri Reticulatae-Radix Glycyrrhizae,Radix Polygalae-Semen Ziziphi Spinosae,and Radix Astragali-Semen Ziziphi Spinosae.Network pharmacology revealed that the cAMP signaling pathway might play a key role in treating insomnia synergistically with HIF-1 signaling pathway,prolactin signaling pathway,chemical carcinogenesis receptor activation,and PI3K-Akt signaling pathway.Molecular docking indicated that there was good binding between the active ingredients of the hub herb pairs and the hub targets.Conclusions This study identified six hub herb pairs for treating insomnia in TCM.These hub herb pairs may synergistically treat insomnia with HIF-1 signaling pathway,prolactin signaling pathway,chemical carcinogenesis receptor activation,and PI3K-Akt signaling pathway through the cAMP signaling pathway.展开更多
Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corre...Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.展开更多
Objective To analyze various herbal combinations in Treatise on Exogenous Febrile Diseases(Shang Han Lun,《伤寒论》)and Synopsis of Prescriptions of the Golden Chamber(Jin Gui Yao Lve,《金匮要略》),seeking to identify...Objective To analyze various herbal combinations in Treatise on Exogenous Febrile Diseases(Shang Han Lun,《伤寒论》)and Synopsis of Prescriptions of the Golden Chamber(Jin Gui Yao Lve,《金匮要略》),seeking to identify fundamental rules dictating the selection of herbal combinations through probability models and big data technology.Methods A total of 252 formulae were collected from Treatise on Exogenous Febrile Diseases(Shang Han Lun,《伤寒论》)and Synopsis of Prescriptions of the Golden Chamber(Jin Gui Yao Lve,《金匮要略》)by ZHANG Zhong-Jing.Formulae were then preprocessed with all herb names standardized.The concepts of candidate herb pair and candidate herb pair probability were proposed to analyze the rules of combinations in classical formulae based on probability statistics.MapReduce parallel computing framework of distributed big data technology was adopted to analyze large data samples combined with inverted index algorithm.Results The results showed that the core herbs were Glycyrrhizae Radix Rhizoma(Gan Cao,甘草),Cinnamomi Ramulus(Gui Zhi,桂枝),Zingiberis Rhizoma Recens(Sheng Jiang,生姜),Jujubae Fructus(Da Zao,大枣),Paeoniae Radix Alba(Bai Shao,白芍),etc.43 high-frequency pairs co-occurring 10 times or above were extracted,and 35 of these combinations were recognized as traditional herb pairs,such as Cinnamomi Ramulus(Gui Zhi,桂枝)-Glycyrrhizae Radix Rhizoma(Gan Cao,甘草),Zingiberis Rhizoma Recens(Sheng Jiang,生姜)-Jujubae Fructus(Da Zao,大枣),and Cinnamomi Ramulus(Gui Zhi,桂枝)-Ginseng Radix Et Rhizoma(Ren Shen,人参).The other 8 pairs of combinations,such as Paeoniae Radix Alba(Bai Shao,白芍)-Zingiberis Rhizoma Recens(Sheng Jiang,生姜),Paeoniae Radix Alba(Bai Shao,白芍)-Jujubae Fructus(Da Zao,大枣),and Zingiberis Rhizoma Recens(Sheng Jiang,生姜)-Ginseng Radix Et Rhizoma(Ren Shen,人参),were not defined traditionally,but in connection with commonly used herbs.Classical formulae took the core herbs as principles,focusing on tonifying deficiency,strengthening the spleen and the stomach,strengthening the healthy Qi,and eliminating pathogenic factors.The compatibility pattern of properties involved was mainly acrid and sweet,which reflected the compatibility laws of benefiting Qi and tonifying Yang,replenishing Qi and nourishing blood,etc.Conclusions The research of classical formulae provides common understanding of some basic rules that have been adopted to tackle common illnesses/diseases using herbal medicine.The results help to reinforce theoretical understanding and development of traditional Chinese medicine(TCM),and revealing the hidden rules of combination in TCM data.Analyzing wider data samples of various herbal combinations through computation and big data technology can further optimize the use of TCM.展开更多
Objective To analyze the mechanism of action and compatibility of the active compounds of the traditional herb pair Bupleuri Radix(Chai Hu,CH,柴胡)-Paeoniae Radix Alba(Bai Shao,BS,白芍).Methods All chemical compounds ...Objective To analyze the mechanism of action and compatibility of the active compounds of the traditional herb pair Bupleuri Radix(Chai Hu,CH,柴胡)-Paeoniae Radix Alba(Bai Shao,BS,白芍).Methods All chemical compounds related to CH and BS were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Integrated Database(TCMID),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(Batman-TCM),Traditional Chinese Medicine Database@Taiwan(TCM Database@Taiwan),and the literature.Relevant compounds were screened for oral bioavailability(OB),drug-likeness(DL),and the Caco-2 cell model.The Uniprot,Genecard,and CTD databases were used to obtain information on potential targets and diseases of associated compounds.Based on this,Cytoscape 3.2.1 software,GO enrichment analysis,and KEGG pathway enrichment were used to analyze the potential mechanism of action and pathways of the CH-BS drug combination.Results A total of 23 active compounds of CH and BS were indentified after meeting specific criteria by network pharmacology,showing 79 predicted targets of active compounds.Among them,all targets were associated with 344 diseases,and the compounds in CH and BS were connected to 94 pathways and biological,such as calcium signaling pathway,neuroactive ligand-receptor interaction and TNF signaling pathway.Conclusions Our results preliminarily validated the main compounds in CH-BS herb pair interacted with multiple targets in different diseases,and the molecular mechanism of these compounds involves multiple pathways,thereby establishing a good foundation for further studies.展开更多
Objective: To explore the molecular mechanism of Magnoliae Flos and Xanthii Fructus herb pair for allergic rhinitis based on network pharmacology. Methods: From the Traditional Chinese Medicine Systems Pharmacology da...Objective: To explore the molecular mechanism of Magnoliae Flos and Xanthii Fructus herb pair for allergic rhinitis based on network pharmacology. Methods: From the Traditional Chinese Medicine Systems Pharmacology database, Uniprot database, and Gene Cards database, the relevant chemical constituents information, pharmacokinetic information and hub target of allergic rhinitis were obtained. The protein-protein interaction network was constructed by STRING online database, analyzed and showed by the Cytoscape software. The screened target information was analyzed by the Metascape database for Gene Ontology biological function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Results: Main components of Magnoliae Flos and Xanthii Fructus herb pair, such as aloe-emodin, stigmasterol, beta-sitosterol and Yangambin, depend on the interaction of Nitric Oxide Synthase 3, Tumor Necrosis Factor, Caspase-3 and other functions involve G protein-coupled (amine) receptor activity, RNA polymerase II basic transcription factor binding, protease binding, heme binding, and integrin binding;can regulate calcium signal pathway, serotonergic synapse, Kyoto Encyclopedia of Genes and Genomes signal pathway, tryptophan inflammatory mediator regulation pathway, estrogen signal pathway alone or in combination, and play a role in the treatment of allergic rhinitis. Conclusion: Magnoliae Flos combined with Xanthii Fructus can regulate biomolecular network in multiple targets and pathways to treat allergic rhinitis.展开更多
According to the theory of traditional Chinese medicine,based on the four properties and five flavors of traditional Chinese medicines,the lifting and lowering theory and channel tropism,Professor Chen combined with t...According to the theory of traditional Chinese medicine,based on the four properties and five flavors of traditional Chinese medicines,the lifting and lowering theory and channel tropism,Professor Chen combined with the theory of traditional Chinese medicine and constitution identification to prescribe for patients and used herb pairs to treat many kinds of pulmonary diseases.And he has achieved good clinical effect by"treatment methods selection according to syndromes".His experience in medication and compatibility mechanism are worthy of further exploration and promotion by scholars.展开更多
Objective:Liver cirrhosis is a disease that seriously damages human health.Traditional Chinese Medicine(TCM)formulae have a good therapeutic effect on cirrhosis,and the herb pair is the smallest unit in formula compat...Objective:Liver cirrhosis is a disease that seriously damages human health.Traditional Chinese Medicine(TCM)formulae have a good therapeutic effect on cirrhosis,and the herb pair is the smallest unit in formula compatibility,which is important for improving the therapeutic effect.Therefore,identifying core herb pairs among TCM formulae is key.Methods:We mined the data of TCM formulae for the treatment of cirrhosis in the China National Intellectual Property Administration for the first time and analyzed their herb characteristics and association rules.We screened 405 patented TCM formulae,including 953 herbs.Based on frequency statistics and association rules,we determined“Astragali Radix-Salviae Miltiorrhizae Radix Et Rhizoma”as the core herb pair.Results:Six active compounds,Isorhamnetin,Formononetin,Calycosin,Cryptotanshinone,Dihydrotanshinone I,and Tanshinone II A,were screened out based on previous studies and network pharmacology.We found that SRC,TP53,HSP90AA1,MAPK3,MAPK1,and STAT3 played pivotal roles in treating cirrhosis.Interestingly,molecular docking indicated that MAPK3 might be a potential pharmacological target for cirrhosis.Conclusion:We preliminarily predicted and verified the pharmacological and molecular mechanism of“Astragali Radix-Salviae Miltiorrhizae Radix Et Rhizoma”in treating cirrhosis.This can expand the scope of TCM in the treatment of cirrhosis,guide people to use clinical formulae,and provide valuable insights for further drug discovery studies.展开更多
Background: The Danshen-Honghua herb pair (DHHP) is a common modern Chinese medicine pair for activating blood circulation and resolving blood stasis. It has been used for centuries to treat cardiovascular and cerebro...Background: The Danshen-Honghua herb pair (DHHP) is a common modern Chinese medicine pair for activating blood circulation and resolving blood stasis. It has been used for centuries to treat cardiovascular and cerebrovascular diseases and is often found in some herbal compounds for treating cardiovascular diseases. The aim of this study was to explore the effects of DHHP on the intestinal flora of rats with acute myocardial ischemia and its microbial transformation in vitro. Methods: In this study, we investigated the protective effect of DHHP on isoproterenol-induced acute myocardial ischemia in rats based on metagenomic sequencing technology, and further characterized the in vitro metabolic transformation products of DHHP, so as to investigate its anti-myocardial ischemic efficacy material basis. Results: Pharmacodynamic results demonstrated that DHHP significantly ameliorated pathological changes and improved abnormal cardiac enzyme levels in acute myocardial ischemia rats. In addition, metagenomic analysis showed the efficacy of DHHP in ameliorating the isoproterenol-induced modifications of the intestinal flora in rats. Specifically, DHHP promoted the growth of the intestinal potential probiotics such as Lactobacillus while suppressing the pathogenic bacteria, including Escherichia and Streptococcus. The in vitro metabolism results showed that the DHHP’s active components underwent primarily phase I metabolism through hydroxylation, decarboxylation, and dehydration inversions in the isolated intestinal flora of acute myocardial ischemia rats and in phase II through sulfation esterification and methylation reactions. Conclusion: The results suggest that there may be a bidirectional regulatory effect between DHHP and intestinal flora, which is important to explain the pharmacological mechanism of DHHP.展开更多
Objective： To investigate the antipyretic mechanism of Herba Ephedrae （Eph）-Ramulus Cinnamomi （RC） herb pair on yeast-induced pyrexia in rats. Methods： Totally 30 qualified male SD rats were randomly assigned to...Objective： To investigate the antipyretic mechanism of Herba Ephedrae （Eph）-Ramulus Cinnamomi （RC） herb pair on yeast-induced pyrexia in rats. Methods： Totally 30 qualified male SD rats were randomly assigned to the normal control （NC） group, the pyrexia model （model） group, the Eph, RC and Eph-RC treatment groups by a random digital table, 6 rats in each group. Each rat received a 20% aqueous suspension of yeast （10 mL/kg） except the NC group. The 3 treatment groups were administered 8.1, 5.4 and 13.5 g/kg Eph, RC and Eph-RC respectively at 5 and 12 h after yeast injection, the NC group and the model groups were administered equal volume of distilled water. Rectal temperatures were measured at 0, 6, 8, 10, 12, 15, 18, 24 and 30 h and urine was collected prior to yeast injection and at 6, 10, 18, 24, 30, and 36 h after yeast injection. Then urine metabolomic profiling by gas chromatography tandem mass spectrometry, coupled with multivariate statistical analysis and pattern recognition techniques were used to explore the antipyretic effects of Eph-RC. Partial least squares discriminate analysis was used to analyze the metabolomics dataset including classification and regression in metabolomics plot profiling. Results： Compared with the NC group, rectal temperatures were significantly higher in the model group （P〈0.01）, while 3 treatment groups decreased significantly compared with the model group （P〈0.05 or P〈0.01）. Rectal temperatures of Eph-RC-treated rats started to go down at 6 h, and markedly decreased at 8, 12, 15, 18 and 24 h （P〈0.05 or P〈0.01）, while those of the Eph and RC groups had decreased firstly at 8 h and were markedly lower at 12 h （P〈0.05 or P〈0.01）. Seventeen potential biomarkers related to pyrexia were confirmed and identified, including pyruvic acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic acid, citrate and so on. Eight potential alterations of metabolic pathways including phenylalanine metabolism, citrate cycle, tryptophan metabolism, biosynthesis of valine, leucine and isoleucine, were identified in relation to the antipyretic effects of Eph-RC using MetPA software. Conclusion： The antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved correction of perturbed amino acid, fatty acid, and carbohydrate metabolism according to the metabolic pathway analysis with MetPA.展开更多
Objective To investigate the metabolic routes and metabolites of Rehmannia glutinosa and Cornus officinalis herb pair produced by gut microbiome from rats.Methods A rapid and sensitive ultra-performance liquid chromat...Objective To investigate the metabolic routes and metabolites of Rehmannia glutinosa and Cornus officinalis herb pair produced by gut microbiome from rats.Methods A rapid and sensitive ultra-performance liquid chromatography/quadrupole-time-offlight mass spectrometry（UPLC-Q-TOF/MS） technique combined with Metabolynx？software was established and successfully applied to identify the metabolites of the main bioactive components in the herb pair extract by rat intestinal bacteria.Results Four parent compounds（loganin,morroniside,catalpol,and acteoside） and their eight corresponding metabolites were detected and tentatively identified by the characteristics of their protonated ions.Hydrogenated and demethylated loganetin,dehydroxylated morronisid aglycone,caffeic acid,and its methylated product were the main metabolites.These metabolites suggested that the glycosides were firstly hydrolyzed to their aglycones by hydrolytic enzymes of the enteric microbial flora and subsequently to the other metabolites through hydrogenation,（de）-methylation,and de-hydroxylation.Conclusion The results may be helpful for the further investigation of the pharmacokinetic study of R.glutinosa and C.officinalis herb pair in vivo.展开更多
OBJECTIVE: To investigate the most effective weight ratio of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) used to produce decoction for the treatment of abnormal uterine bleeding(AUB) in rat...OBJECTIVE: To investigate the most effective weight ratio of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) used to produce decoction for the treatment of abnormal uterine bleeding(AUB) in rats with incomplete abortion, and to study the possible mechanism. METHODS: The models of AUB were established by incomplete drug abortion with mifepristone and misoprostol in pregnant rats. The therapeutic effects of decoctions made by eight different weight ratios of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) were observed. RESULTS: Statistical analysis revealed that the most effective weight ratio of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) to treat AUB in this study was 2∶1. CONCLUSION: The insights gained from this study would improve understanding of the mechanisms involved in the effect of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) on AUB.展开更多
"Herb-Pairs",also known as pair drugs,refers to a prescription consisted of two relatively fixed traditional Chinese medicine,is the most basic,most simple and most common form of medication prescription in ..."Herb-Pairs",also known as pair drugs,refers to a prescription consisted of two relatively fixed traditional Chinese medicine,is the most basic,most simple and most common form of medication prescription in traditional Chinese medicine compound compatibility.It is not a random combination of two herbs,nor is the simple accumulation of efficacy,but the simple and delicate experience of ancient Chinese medicine practitioners.As a bridge between single drug and prescriptions,it is the embodiment of the regular and dialectical connotation.Therefore,research on Herb-Pairs has always been the most basic and most important entry point for compound compatibility studies.However,the interaction between herbs and herbs is an effect with a downside as well as benefits.The beneficial herb-herb interaction in Herb-Pairs include mutual promotion,mutual enhancement,mutual restraint between two drugs and counteract toxicity of another drug.And the harmful herb-herb interaction in Herb-Pairs includes mutual inhibition and antagonism.Al of these interactions areby means of affecting the metabolism of components to play a therapeutic effect.Using the pharmacokinetic-pharmacodynamic(PK-PD)binding model,the combination of drug metabolism and pharmacodynamics can further elucidate the influence on effect caused by drug concentration and metabolism,which can help elucidate the mechanism of drug action.Consequently,in this review,the herb-herb interactions in terms of pharmacokinetic were summarized to elucidate rule of TCM compatibility.展开更多
Objective:Using Chinese patents in force to investigate the frequency and patterns of Chinese herbal extract combinations claiming to treat heart disease.Methods:Patent documents were retrieved from the official websi...Objective:Using Chinese patents in force to investigate the frequency and patterns of Chinese herbal extract combinations claiming to treat heart disease.Methods:Patent documents were retrieved from the official website of the State Intellectual Property Office of the People’s Republic China.Cluster,frequency,and fuzzy cluster analyses were applied.Results:A high number of patents in force included high-frequency herbs such as Salvia miltiorrhiza,Panax ginseng,and Panax notoginseng,as well as high-frequency herbal families such as Araliaceae,Leguminosae,Labiatae,and Umbelliferae.Herb pairs such as P.ginsengþOphiopogon japonicus,S.miltiorrhizaþDalbergia odorifera,and P.ginsengþSchisandra chinensis are also commonly used,as well as herbal family pairs such as AraliaceaeþLiliaceae,LauraceaeþLeguminosae,and AraliaceaeþSchisandraceae.Traditional treatment principles for preventing and treating heart diseases was most-commonly based on simultaneously treating the liver and heart and treating the lung and spleen secondarily for choosing herbal combinations.Conclusion:Most of the high-frequency Chinese herbs in the patents investigated belong to the high-frequency herbal families,and herb pairs were commonly selected to coincide with the commonly-used herbal family pairs.Low-frequency Chinese herbs were also used,but generally belonged to the high-frequency herbal families,and were therefore similar to the highfrequency herbs in terms of traditional categories of taste and channel entered.The results reflect the use of traditional principles of formula composition,and suggest that these principles may indeed be an effective guide for further research and development of Chinese herbal extract combinations to prevent and treat heart diseases.展开更多
Objective:To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge(S.miltiorrhiza,Dan Shen)and C.tinctorius L.(C.tinctorius,Hong Hua)as an herb pair through network pharmacology and su...Objective:To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge(S.miltiorrhiza,Dan Shen)and C.tinctorius L.(C.tinctorius,Hong Hua)as an herb pair through network pharmacology and subsequent experimental validation.Methods:Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of s.miltiorrhiza and C.tinctorius as herb pair.Molecular docking was used to verify the binding of the components of these herbs and their potential targets.An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects,which were evaluated using the combination index.Western blot was performed to detect the protein expression of these targets.Results:Network pharmacology analysis revealed 5 pathways and 8 core targets of s.miltiorrhiza and C.tinctorius in myocardial protection.Five of the core targets were enriched in the hypoxia-inducible factor-1(HIF-1)signaling pathway.S.miltiorrhiza-C.tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway.As an upstream gene of the HIF-1 pathway,STAT3 can be activated by the active ingredients cryptotanshinone(Ctan),salvianolic acid B(Sal.B),and myricetin(Myric).Cell experiments revealed that Myric,Sal.B,and Ctan also exhibited synergistic myocardial protective activity.Molecular docking verified the strong binding of Myric,Sal.B,and Ctan to STAT3.Western blot further showed that the active ingredients synergistically upregulated the protein expressionof STAT3.Conclusion:The pharmacodynamic transmission analysis revealed that the active ingredients of S.miltiorrhiza and C.tinctorius can synergistically resist ischemia through various targets and pathways.This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.展开更多
基金National Natural Science Foundation of China(82360905)Gansu Provincial University Teachers'Innovation Fund Projects(2023A-092 and 2024B-109).
文摘Objective To explore the medication rules of traditional Chinese medicine(TCM)and mechanism of action of hub herb pairs for treating insomnia.Methods Totally 104 prescriptions were statistically analyzed.The association rule algorithm was applied to mine the hub herb pairs.Network pharmacology was utilized to analyze the mechanism of the hub herb pairs,while molecular docking was applied to simulate the interaction between receptors and herb molecules,thereby predicting their binding affinities.Results The most frequently used herbs in TCM prescriptions for treating insomnia included Semen Ziziphi Spinosae,Radix Glycyrrhizae,Radix et Rhizoma Ginseng,and Poria cum Radix Pini.Among them,the most commonly used were the supplementing herbs,followed by heat-clearing,mind-calming,and exterior-releasing ones,with their properties of warm and cold,flavors of sweet,Pungent,and bitter,and meridian tropisms of liver,lungs,spleen,kidneys,heart,and stomach.The hub herb pairs based on the association rules included Radix Astragali-Radix et Rhizoma Ginseng,Rhizoma Chuanxiong-Radix Glycyrrhizae,Seman Platycladi-Semen Ziziphi Spinosae,Pericarpium Citri Reticulatae-Radix Glycyrrhizae,Radix Polygalae-Semen Ziziphi Spinosae,and Radix Astragali-Semen Ziziphi Spinosae.Network pharmacology revealed that the cAMP signaling pathway might play a key role in treating insomnia synergistically with HIF-1 signaling pathway,prolactin signaling pathway,chemical carcinogenesis receptor activation,and PI3K-Akt signaling pathway.Molecular docking indicated that there was good binding between the active ingredients of the hub herb pairs and the hub targets.Conclusions This study identified six hub herb pairs for treating insomnia in TCM.These hub herb pairs may synergistically treat insomnia with HIF-1 signaling pathway,prolactin signaling pathway,chemical carcinogenesis receptor activation,and PI3K-Akt signaling pathway through the cAMP signaling pathway.
基金the National Natural Science Foundation of China(No.82204250)China Postdoctoral Science Foundation(No.2021M693961)+2 种基金Young and Middle-Aged Talent Project of Hubei Provincial Department of Education(No.Q20222808)Hubei University of Science and Technology Doctoral Startup Fund Project(No.BK202029)Outstanding Young and Middle-Aged Scientific and Technological Innovation Team in Colleges and Universities in Hubei Province(No.T2021022).
文摘Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.
基金funding support from the Key Technology Research and Development Program from Ministry of Science and Technology of the People’s Republic of China (No. 2017YFC1703306)Key Project of Science and Technology of Hunan Province (No. 2017SK2111)+2 种基金Natural Science Foundation of Hunan Province (No. 2018JJ2301)Scientific Research Foundation of Hunan Provincial Education Department (No. 18A227, No. 18C0380 and No. 18K070)Open Fund for Computer Science and Technology of Hunan University of Chinese Medicine (No. 2018JK04)
文摘Objective To analyze various herbal combinations in Treatise on Exogenous Febrile Diseases(Shang Han Lun,《伤寒论》)and Synopsis of Prescriptions of the Golden Chamber(Jin Gui Yao Lve,《金匮要略》),seeking to identify fundamental rules dictating the selection of herbal combinations through probability models and big data technology.Methods A total of 252 formulae were collected from Treatise on Exogenous Febrile Diseases(Shang Han Lun,《伤寒论》)and Synopsis of Prescriptions of the Golden Chamber(Jin Gui Yao Lve,《金匮要略》)by ZHANG Zhong-Jing.Formulae were then preprocessed with all herb names standardized.The concepts of candidate herb pair and candidate herb pair probability were proposed to analyze the rules of combinations in classical formulae based on probability statistics.MapReduce parallel computing framework of distributed big data technology was adopted to analyze large data samples combined with inverted index algorithm.Results The results showed that the core herbs were Glycyrrhizae Radix Rhizoma(Gan Cao,甘草),Cinnamomi Ramulus(Gui Zhi,桂枝),Zingiberis Rhizoma Recens(Sheng Jiang,生姜),Jujubae Fructus(Da Zao,大枣),Paeoniae Radix Alba(Bai Shao,白芍),etc.43 high-frequency pairs co-occurring 10 times or above were extracted,and 35 of these combinations were recognized as traditional herb pairs,such as Cinnamomi Ramulus(Gui Zhi,桂枝)-Glycyrrhizae Radix Rhizoma(Gan Cao,甘草),Zingiberis Rhizoma Recens(Sheng Jiang,生姜)-Jujubae Fructus(Da Zao,大枣),and Cinnamomi Ramulus(Gui Zhi,桂枝)-Ginseng Radix Et Rhizoma(Ren Shen,人参).The other 8 pairs of combinations,such as Paeoniae Radix Alba(Bai Shao,白芍)-Zingiberis Rhizoma Recens(Sheng Jiang,生姜),Paeoniae Radix Alba(Bai Shao,白芍)-Jujubae Fructus(Da Zao,大枣),and Zingiberis Rhizoma Recens(Sheng Jiang,生姜)-Ginseng Radix Et Rhizoma(Ren Shen,人参),were not defined traditionally,but in connection with commonly used herbs.Classical formulae took the core herbs as principles,focusing on tonifying deficiency,strengthening the spleen and the stomach,strengthening the healthy Qi,and eliminating pathogenic factors.The compatibility pattern of properties involved was mainly acrid and sweet,which reflected the compatibility laws of benefiting Qi and tonifying Yang,replenishing Qi and nourishing blood,etc.Conclusions The research of classical formulae provides common understanding of some basic rules that have been adopted to tackle common illnesses/diseases using herbal medicine.The results help to reinforce theoretical understanding and development of traditional Chinese medicine(TCM),and revealing the hidden rules of combination in TCM data.Analyzing wider data samples of various herbal combinations through computation and big data technology can further optimize the use of TCM.
基金funding support from the the National Natural Science Foundation of China (No. 81573780)High-level Hospital Construction (No. 211010010120)
文摘Objective To analyze the mechanism of action and compatibility of the active compounds of the traditional herb pair Bupleuri Radix(Chai Hu,CH,柴胡)-Paeoniae Radix Alba(Bai Shao,BS,白芍).Methods All chemical compounds related to CH and BS were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Integrated Database(TCMID),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(Batman-TCM),Traditional Chinese Medicine Database@Taiwan(TCM Database@Taiwan),and the literature.Relevant compounds were screened for oral bioavailability(OB),drug-likeness(DL),and the Caco-2 cell model.The Uniprot,Genecard,and CTD databases were used to obtain information on potential targets and diseases of associated compounds.Based on this,Cytoscape 3.2.1 software,GO enrichment analysis,and KEGG pathway enrichment were used to analyze the potential mechanism of action and pathways of the CH-BS drug combination.Results A total of 23 active compounds of CH and BS were indentified after meeting specific criteria by network pharmacology,showing 79 predicted targets of active compounds.Among them,all targets were associated with 344 diseases,and the compounds in CH and BS were connected to 94 pathways and biological,such as calcium signaling pathway,neuroactive ligand-receptor interaction and TNF signaling pathway.Conclusions Our results preliminarily validated the main compounds in CH-BS herb pair interacted with multiple targets in different diseases,and the molecular mechanism of these compounds involves multiple pathways,thereby establishing a good foundation for further studies.
基金This study was supported by the Discipline Innovation Team Construction Project of the Second Affiliated Hospital of Shaanxi University of Chinese Medicine(2020XKTD-A02).
文摘Objective: To explore the molecular mechanism of Magnoliae Flos and Xanthii Fructus herb pair for allergic rhinitis based on network pharmacology. Methods: From the Traditional Chinese Medicine Systems Pharmacology database, Uniprot database, and Gene Cards database, the relevant chemical constituents information, pharmacokinetic information and hub target of allergic rhinitis were obtained. The protein-protein interaction network was constructed by STRING online database, analyzed and showed by the Cytoscape software. The screened target information was analyzed by the Metascape database for Gene Ontology biological function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Results: Main components of Magnoliae Flos and Xanthii Fructus herb pair, such as aloe-emodin, stigmasterol, beta-sitosterol and Yangambin, depend on the interaction of Nitric Oxide Synthase 3, Tumor Necrosis Factor, Caspase-3 and other functions involve G protein-coupled (amine) receptor activity, RNA polymerase II basic transcription factor binding, protease binding, heme binding, and integrin binding;can regulate calcium signal pathway, serotonergic synapse, Kyoto Encyclopedia of Genes and Genomes signal pathway, tryptophan inflammatory mediator regulation pathway, estrogen signal pathway alone or in combination, and play a role in the treatment of allergic rhinitis. Conclusion: Magnoliae Flos combined with Xanthii Fructus can regulate biomolecular network in multiple targets and pathways to treat allergic rhinitis.
基金"Taishan scholar"construction project of Shandong Provincial People's Government(No.ts201712096)Shandong Province 2019-2020 science and technology development plan project of traditional Chinese medicine(special subject of traditional Chinese medicine classics prescription):a development project of diagnosis and treatment guide for common diseases of primary pulmonary disease department treated by traditional Chinese medicine classics prescription(No.2019-0967)。
文摘According to the theory of traditional Chinese medicine,based on the four properties and five flavors of traditional Chinese medicines,the lifting and lowering theory and channel tropism,Professor Chen combined with the theory of traditional Chinese medicine and constitution identification to prescribe for patients and used herb pairs to treat many kinds of pulmonary diseases.And he has achieved good clinical effect by"treatment methods selection according to syndromes".His experience in medication and compatibility mechanism are worthy of further exploration and promotion by scholars.
基金supported by the National Key R&D Program of China (2018YFC1706506)the National Natural Science Foundation of China Youth Program (81703921)the Tianjin Key Medical Discipline (Specialty)Construction Project。
文摘Objective:Liver cirrhosis is a disease that seriously damages human health.Traditional Chinese Medicine(TCM)formulae have a good therapeutic effect on cirrhosis,and the herb pair is the smallest unit in formula compatibility,which is important for improving the therapeutic effect.Therefore,identifying core herb pairs among TCM formulae is key.Methods:We mined the data of TCM formulae for the treatment of cirrhosis in the China National Intellectual Property Administration for the first time and analyzed their herb characteristics and association rules.We screened 405 patented TCM formulae,including 953 herbs.Based on frequency statistics and association rules,we determined“Astragali Radix-Salviae Miltiorrhizae Radix Et Rhizoma”as the core herb pair.Results:Six active compounds,Isorhamnetin,Formononetin,Calycosin,Cryptotanshinone,Dihydrotanshinone I,and Tanshinone II A,were screened out based on previous studies and network pharmacology.We found that SRC,TP53,HSP90AA1,MAPK3,MAPK1,and STAT3 played pivotal roles in treating cirrhosis.Interestingly,molecular docking indicated that MAPK3 might be a potential pharmacological target for cirrhosis.Conclusion:We preliminarily predicted and verified the pharmacological and molecular mechanism of“Astragali Radix-Salviae Miltiorrhizae Radix Et Rhizoma”in treating cirrhosis.This can expand the scope of TCM in the treatment of cirrhosis,guide people to use clinical formulae,and provide valuable insights for further drug discovery studies.
基金supported by the National Natural Science Foundation of China(CN)(No.81974544).
文摘Background: The Danshen-Honghua herb pair (DHHP) is a common modern Chinese medicine pair for activating blood circulation and resolving blood stasis. It has been used for centuries to treat cardiovascular and cerebrovascular diseases and is often found in some herbal compounds for treating cardiovascular diseases. The aim of this study was to explore the effects of DHHP on the intestinal flora of rats with acute myocardial ischemia and its microbial transformation in vitro. Methods: In this study, we investigated the protective effect of DHHP on isoproterenol-induced acute myocardial ischemia in rats based on metagenomic sequencing technology, and further characterized the in vitro metabolic transformation products of DHHP, so as to investigate its anti-myocardial ischemic efficacy material basis. Results: Pharmacodynamic results demonstrated that DHHP significantly ameliorated pathological changes and improved abnormal cardiac enzyme levels in acute myocardial ischemia rats. In addition, metagenomic analysis showed the efficacy of DHHP in ameliorating the isoproterenol-induced modifications of the intestinal flora in rats. Specifically, DHHP promoted the growth of the intestinal potential probiotics such as Lactobacillus while suppressing the pathogenic bacteria, including Escherichia and Streptococcus. The in vitro metabolism results showed that the DHHP’s active components underwent primarily phase I metabolism through hydroxylation, decarboxylation, and dehydration inversions in the isolated intestinal flora of acute myocardial ischemia rats and in phase II through sulfation esterification and methylation reactions. Conclusion: The results suggest that there may be a bidirectional regulatory effect between DHHP and intestinal flora, which is important to explain the pharmacological mechanism of DHHP.
基金Supported by the National Natural Science Foundation of China(No.81030066)
文摘Objective： To investigate the antipyretic mechanism of Herba Ephedrae （Eph）-Ramulus Cinnamomi （RC） herb pair on yeast-induced pyrexia in rats. Methods： Totally 30 qualified male SD rats were randomly assigned to the normal control （NC） group, the pyrexia model （model） group, the Eph, RC and Eph-RC treatment groups by a random digital table, 6 rats in each group. Each rat received a 20% aqueous suspension of yeast （10 mL/kg） except the NC group. The 3 treatment groups were administered 8.1, 5.4 and 13.5 g/kg Eph, RC and Eph-RC respectively at 5 and 12 h after yeast injection, the NC group and the model groups were administered equal volume of distilled water. Rectal temperatures were measured at 0, 6, 8, 10, 12, 15, 18, 24 and 30 h and urine was collected prior to yeast injection and at 6, 10, 18, 24, 30, and 36 h after yeast injection. Then urine metabolomic profiling by gas chromatography tandem mass spectrometry, coupled with multivariate statistical analysis and pattern recognition techniques were used to explore the antipyretic effects of Eph-RC. Partial least squares discriminate analysis was used to analyze the metabolomics dataset including classification and regression in metabolomics plot profiling. Results： Compared with the NC group, rectal temperatures were significantly higher in the model group （P〈0.01）, while 3 treatment groups decreased significantly compared with the model group （P〈0.05 or P〈0.01）. Rectal temperatures of Eph-RC-treated rats started to go down at 6 h, and markedly decreased at 8, 12, 15, 18 and 24 h （P〈0.05 or P〈0.01）, while those of the Eph and RC groups had decreased firstly at 8 h and were markedly lower at 12 h （P〈0.05 or P〈0.01）. Seventeen potential biomarkers related to pyrexia were confirmed and identified, including pyruvic acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic acid, citrate and so on. Eight potential alterations of metabolic pathways including phenylalanine metabolism, citrate cycle, tryptophan metabolism, biosynthesis of valine, leucine and isoleucine, were identified in relation to the antipyretic effects of Eph-RC using MetPA software. Conclusion： The antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved correction of perturbed amino acid, fatty acid, and carbohydrate metabolism according to the metabolic pathway analysis with MetPA.
基金National Natural Science Foundation of China(No.81072996,81102743)Priority Academic Programs Development of Jiangsu Higher Education Institutions(PAPD)
文摘Objective To investigate the metabolic routes and metabolites of Rehmannia glutinosa and Cornus officinalis herb pair produced by gut microbiome from rats.Methods A rapid and sensitive ultra-performance liquid chromatography/quadrupole-time-offlight mass spectrometry（UPLC-Q-TOF/MS） technique combined with Metabolynx？software was established and successfully applied to identify the metabolites of the main bioactive components in the herb pair extract by rat intestinal bacteria.Results Four parent compounds（loganin,morroniside,catalpol,and acteoside） and their eight corresponding metabolites were detected and tentatively identified by the characteristics of their protonated ions.Hydrogenated and demethylated loganetin,dehydroxylated morronisid aglycone,caffeic acid,and its methylated product were the main metabolites.These metabolites suggested that the glycosides were firstly hydrolyzed to their aglycones by hydrolytic enzymes of the enteric microbial flora and subsequently to the other metabolites through hydrogenation,（de）-methylation,and de-hydroxylation.Conclusion The results may be helpful for the further investigation of the pharmacokinetic study of R.glutinosa and C.officinalis herb pair in vivo.
文摘OBJECTIVE: To investigate the most effective weight ratio of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) used to produce decoction for the treatment of abnormal uterine bleeding(AUB) in rats with incomplete abortion, and to study the possible mechanism. METHODS: The models of AUB were established by incomplete drug abortion with mifepristone and misoprostol in pregnant rats. The therapeutic effects of decoctions made by eight different weight ratios of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) were observed. RESULTS: Statistical analysis revealed that the most effective weight ratio of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) to treat AUB in this study was 2∶1. CONCLUSION: The insights gained from this study would improve understanding of the mechanisms involved in the effect of Qiancao(Radix Rubiae Cordifoliae) and Haipiaoxiao(Endoconcha Sepiellae) on AUB.
文摘"Herb-Pairs",also known as pair drugs,refers to a prescription consisted of two relatively fixed traditional Chinese medicine,is the most basic,most simple and most common form of medication prescription in traditional Chinese medicine compound compatibility.It is not a random combination of two herbs,nor is the simple accumulation of efficacy,but the simple and delicate experience of ancient Chinese medicine practitioners.As a bridge between single drug and prescriptions,it is the embodiment of the regular and dialectical connotation.Therefore,research on Herb-Pairs has always been the most basic and most important entry point for compound compatibility studies.However,the interaction between herbs and herbs is an effect with a downside as well as benefits.The beneficial herb-herb interaction in Herb-Pairs include mutual promotion,mutual enhancement,mutual restraint between two drugs and counteract toxicity of another drug.And the harmful herb-herb interaction in Herb-Pairs includes mutual inhibition and antagonism.Al of these interactions areby means of affecting the metabolism of components to play a therapeutic effect.Using the pharmacokinetic-pharmacodynamic(PK-PD)binding model,the combination of drug metabolism and pharmacodynamics can further elucidate the influence on effect caused by drug concentration and metabolism,which can help elucidate the mechanism of drug action.Consequently,in this review,the herb-herb interactions in terms of pharmacokinetic were summarized to elucidate rule of TCM compatibility.
文摘Objective:Using Chinese patents in force to investigate the frequency and patterns of Chinese herbal extract combinations claiming to treat heart disease.Methods:Patent documents were retrieved from the official website of the State Intellectual Property Office of the People’s Republic China.Cluster,frequency,and fuzzy cluster analyses were applied.Results:A high number of patents in force included high-frequency herbs such as Salvia miltiorrhiza,Panax ginseng,and Panax notoginseng,as well as high-frequency herbal families such as Araliaceae,Leguminosae,Labiatae,and Umbelliferae.Herb pairs such as P.ginsengþOphiopogon japonicus,S.miltiorrhizaþDalbergia odorifera,and P.ginsengþSchisandra chinensis are also commonly used,as well as herbal family pairs such as AraliaceaeþLiliaceae,LauraceaeþLeguminosae,and AraliaceaeþSchisandraceae.Traditional treatment principles for preventing and treating heart diseases was most-commonly based on simultaneously treating the liver and heart and treating the lung and spleen secondarily for choosing herbal combinations.Conclusion:Most of the high-frequency Chinese herbs in the patents investigated belong to the high-frequency herbal families,and herb pairs were commonly selected to coincide with the commonly-used herbal family pairs.Low-frequency Chinese herbs were also used,but generally belonged to the high-frequency herbal families,and were therefore similar to the highfrequency herbs in terms of traditional categories of taste and channel entered.The results reflect the use of traditional principles of formula composition,and suggest that these principles may indeed be an effective guide for further research and development of Chinese herbal extract combinations to prevent and treat heart diseases.
基金supported by the National Natural Science Foundation of China(81703947)the Fundamental Research Funds for the Central Universities(2019-JYB-XJSJJ-011).
文摘Objective:To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge(S.miltiorrhiza,Dan Shen)and C.tinctorius L.(C.tinctorius,Hong Hua)as an herb pair through network pharmacology and subsequent experimental validation.Methods:Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of s.miltiorrhiza and C.tinctorius as herb pair.Molecular docking was used to verify the binding of the components of these herbs and their potential targets.An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects,which were evaluated using the combination index.Western blot was performed to detect the protein expression of these targets.Results:Network pharmacology analysis revealed 5 pathways and 8 core targets of s.miltiorrhiza and C.tinctorius in myocardial protection.Five of the core targets were enriched in the hypoxia-inducible factor-1(HIF-1)signaling pathway.S.miltiorrhiza-C.tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway.As an upstream gene of the HIF-1 pathway,STAT3 can be activated by the active ingredients cryptotanshinone(Ctan),salvianolic acid B(Sal.B),and myricetin(Myric).Cell experiments revealed that Myric,Sal.B,and Ctan also exhibited synergistic myocardial protective activity.Molecular docking verified the strong binding of Myric,Sal.B,and Ctan to STAT3.Western blot further showed that the active ingredients synergistically upregulated the protein expressionof STAT3.Conclusion:The pharmacodynamic transmission analysis revealed that the active ingredients of S.miltiorrhiza and C.tinctorius can synergistically resist ischemia through various targets and pathways.This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.
