Deciphering suppressive effects of Lianhua Qingwen Capsule on COVID-19 and synergistic effects of its major botanical drug pairs

The COVID-19 pandemic has resulted in excess deaths worldwide.Conventional antiviral medicines have been used to relieve the symptoms,with limited therapeutic effect.In contrast,Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect.The current review aims to:1)uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19;2)verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis;3)investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule;and 4)clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs.Numerous bioactive ingredients in Lianhu Qingwen,such as quercetin,naringenin,β-sitosterol,luteolin,and stigmasterol,were identified to target host cytokines,and to regulate the immune defence in response to COVID-19.Genes including androgen receptor(AR),myeloperoxidase(MPO),epidermal growth factor receptor(EGFR),insulin(INS),and aryl hydrocarbon receptor(AHR)were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19.Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19.Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19.In conclusion,the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed.Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.

Network pharmacology study of drug pair Tubeimu-Zhebeimu in the treatment of breast cancer

Objective:Breast cancer is a malignant tumor endangering women’s safety and health.Clinical medication experience and related studies show that the drug pairs Tubeimu-Zhebeimu has an excellent therapeutic effect on patients with breast cancer,but its treatment mechanism is unclear.In this study,network pharmacology and molecular docking were used to analyze and explore the mechanism of“Tubeimu-Zhebeimu”in treating breast cancer.Methods:Traditional Chinese Medicine Database and Analysis Platform were used to retrieve the chemical constituents of Tubeimu and Zhebeimu,and the relevant targets were predicted through the Swiss Target Prediction Database.Searching the Gene cards,Therapeutic Target Database and Disgenet Database with the keywords“breast cancer”,“mammary cancer”and“mammary adenocarcinoma”obtain disease-related targets.We intersect the disease target with the drug target to obtain the potential drug therapy target.Then the data was imported into Cytoscape 3.9.1 software to construct a compound network of“Disease-Target-Component-Drug”,and the network.Subsequently,using the String Database a“protein-protein interaction network”was constructed and imported into Cytoscape 3.9.1 software for structural optimization and network topology analysis.DAVID was used for Gene Ontolog function enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses,and the results were visualized.The core targets were molecularly docked through AutoDockTools-1.5.6 software and Auto Dock Vina 1.1.2 software.Results:The results showed that the 20 active ingredients in the“Tubeimu-Zhebeimu”includingβ-sitosterol,Chaksine,saponins,and peimuocinine,can treat breast cancer through 139 potential targets including AKT1,AR,TP53,ESR1.Conclusion:The specific mechanism of the drug pairs Tubeimu-Zhebeimu treating breast cancer may be controlling human hormone levels,inducing cell apoptosis,and participating in the P53 protein signaling pathway and PI3K/Akt/mTOR signaling pathway.

Study on the mechanism of“Salvia chinensis and Radix Ranunculi Ternati”drug pair in the treatment of lung cancer

Objective:To explore the molecular biological mechanism of the"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer based on network pharmacology.Methods:Searching the TCMSP database and previous literatures to screen the active compounds which resist lung cancer activity in salvia chinensis and radix ranunculi ternati.The candidate compounds were unified in the DrugBank to find the corresponding drug targets which were corrected to the standard gene names by the UniProt database.The Swiss Target Prediction platform was used to predict other targets.Searching GeneCards,OMIM and DrugBank to obtain genes related to lung cancer.After taking the intersection,the candidate gene target of drug pair in the treatment of lung cancer could be obtained.The"herbs-compounds-targets-disease"network was bulit with Cytoscape,and the PPI network was bulit on the STRING platform while the core network nodes were screened.GO and KEGG analysis on candidate genes was implemented through Metacape platform,and a"pathways-targets"network was bulit to further screen key genes.Results:A total of 16 active compounds in salvia chinensis,18 active compounds in radix ranunculi ternati,164 candidate targets,2443 GO functions and 170 KEGG pathways was obtained.Conclusion:The effective compounds of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer are quercetin,ursolic acid,β-sitosterol and caffeic acid.The key targets are MAPK1,AKT1,PIK3R1,RAF1 and EGFR.GO functions mainly include cytokines,oxidative stress,plasma membrane transmission,protein kinase binding and activity,apoptosis.KEGG could directly regulate pathways in cancer,non-small cells lung cancer pathway and small cell lung cancer pathway.KEGG also involves EGFR tyrosine kinase inhibitor resistance,IL-17,TNF,PI3K-AKT signaling pathway and apoptosis.This study reveals the molecular biological mechanism of"salvia chinensis and radix ranunculi ternati"drug pair in the treatment of lung cancer.It is reasoned that its potential targets affect multiple signaling pathways and ultimately resist the proliferation,differentiation,invasion,metastasis and promote apoptosis of lung cancer cells.Evidence for further experimental study is provided by this study.

Analysis on the Medication Law of Drug Pair Acorus Tatarinowii-Polygala Tenuifolia Based on the Dictionary of Traditional Chinese Medicine Prescriptions

Objective:Using data mining method to dig and sort out the prescriptions with Acorus tatarinowiiPolygala tenuifolia drug pair,and summarize the medication characteristics and compatibility of their prescriptions after preliminary screening.Methods:By searching the Dictionary of Traditional Chinese Medicine Prescriptions,a standardized database of prescriptions was established,and the properties,tastes and meridian tropism of prescriptions were classified,and the indications of prescriptions and core combinations of traditional Chinese medicines were analyzed.Results:178 prescriptions were collected,of which 210 were related.Most of the drugs were warm in nature and sweet in taste,and mainly return to the heart and kidney meridians.Under the same confidence and different support,the core drug combination for treating brain diseases was Acorus tatarinowiiPolygala tenuifolia-Ginseng,and the core drug combination for treating asthenia was Acorus tatarinowii-Poria cocos-Rehmannia glutinosa-Polygala tenuifolia.Conclusion:The compatibility characteristics of the prescriptions containing Acorus Tatarinowii and Polygala tenuifolia in the Dictionary of Traditional Chinese Medicine Prescriptions are remarkable,which provides reference for scientific guidance of clinical rational drug use and basic research of prescriptions containing Acorus tatarinowii and Polygala tenuifolia.

Study on the mechanism of two related Chinese herbs Chenpi-Banxia in the treatment of coronary microvascular dysfunction based on network pharmacology

Objective:By the method of network pharmacology to study the main active compounds,main target genes,critical path and mechanism of the two classical Chinese herbs Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction(CMD).Methods:Obtaining potential active compounds of Chenpi-Banxia from TCMSP,while the targets for CMD were obtained from DrugBank and OMIM databases.Using UniProt database to query the corresponding gene name.The key target of Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction can be obtained by using the intersection of VENNY.The PPI network was screened for the major targets by String and Cytoscape3.7.1.The GO enrichment analysis and KEGG Pathway analyses of major targets were performed by using the DAVID database and use Binformatics to draw bubble map.Finally,the ingredient-major arget-key pathway network was constructed by Cytoscape3.7.1.Results:There were 16 compounds such as naringenin,nobiletin,baicalein.beta-sitosterol etc,and 56 predictive target genes such as AKT1、VEGFA、BCL2、BAX、JUN etc,as well as 20 key pathways including inflammation-related pathway(TNF signaling pathway),pathways related to cardiovascular system(PI3K-Akt signaling pathway),Vascular endothelial growth factor signaling pathway(VEGF signaling pathway),Apoptosis related pathways(Apoptosis)and Hypoxia cell stress signaling pathway(HIF-1 signaling pathway)in the Compounds-Target-Pathway network.Conclusion:The study verified the characteristics of multi-components,multi-targets and integral regulation for Chenpi-Banxia with the application of network pharmacology.It predicted that Chenpi-Banxia couldtreat Coronary Microvascular Dysfunction mainly by protecting endothelial cell function of coronary microcirculation,inhibiting cell apoptosis and affecting inflammatory reaction.

An Empirical Analysis of Director Mingjun Zhao’s Experience in Treating Chronic Heart Failure

With the aggravation of an aging population,the prevalence of chronic heart failure is increasing.As a famous traditional Chinese medicine practitioner in Shaanxi Province,Mingjun Zhao is amicable at using traditional Chinese medicine to treat chronic heart failure.He believes that the pathogenesis of the condition is mainly due to the lack of heart Yang,deficiency of heart Qi,as well as the combination of water and blood stasis.Therefore,in treating this condition,it is essential to warm and nourish heart Yang,replenish Qi to benefit water,and promote blood circulation to remove blood stasis.Based on the standardized treatment used in western medicine,traditional Chinese medicine should be reasonably and accurately combined with it as a drug pair into a prescription,thus highlighting the advantages of the combination of traditional Chinese medicine in the treatment of chronic heart failure to a great extent.

Efficacy of an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair in a rat model of polycystic ovary syndrome

OBJECTIVE:To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis)drug pair(ECD)and investigate its efficacy on polycystic ovary syndrome(PCOS),and its possible mechanism in a rat model of PCOS.METHODS:A network pharmacology approach involving a characteristic drug assessment,active compound and target prediction,PCOS gene collection as well as network analysis was employed.The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target.RESULTS:Six networks were constructed,an active compound-target network for the ECD(C-T network),a drug-target network(D-T network),a related genes network,a targets interaction network,a key genes interaction network,and a gene-pathway network.A total of 41 compounds and 261 targets were identified for the ECD,232 PCOS-related genes,31 cogenes,and 14 pathways.These pathways may be involved in the efficacy of ECD on PCOS.The proteins most involved in the signal pathways for all targets were AKT1,IL6,INSR,ESR,and GSK3B.The AKT1 target was selected for experimental verification.Based on the Western blot and real-time PCR results,the expression of AKT1 in the PCOS model varied after treatment with ECD.CONCLUSIONS:Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS.AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.

Mechanism of'Invigorating Qi and Promoting Blood Circulation'Drug Pair Ginseng-Danshen on Treatment of Ischemic Heart Disease Based on Network Pharmacology

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(PI3 K-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.

Mechanism of the Salvia miltiorrhiza-Codonopsis pilosula drug pair in the treatment of premature ovarian failure based on network pharmacology-molecular docking

Objective: Premature ovarian failure (POF) is a disease characterized by irregular menstruation and results in infertility which markedly affects the reproductive health of women. TheSalvia miltiorrhiza-Codonopsis pilosula drug pair is effective at treating POF;however, knowledge of the mechanisms ofS. miltiorrhiza-C. pilosula in the treatment of POF is lacking. Thus, we carried out network pharmacology and molecular docking to clarify the mechanisms of this drug pair.Methods: The core components and targets ofS. miltiorrhiza-C. pilosula were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database and UniProt database, and the disease targets related to POF were searched using different tools to obtain the overlapping target genes ofS. miltiorrhiza andC. pilosula. A protein interaction network of the intersection target was constructed using STRING database, and the network of "traditional Chinese medicine-active ingredient-intersection target-disease" and "pathways-targets" was constructed using Cytoscape 3.8.0. The DAVID online tool was also used to determine the gene ontology functions and Kyoto Encyclopedia of Genes and Genomes pathways associated with the intersection target genes. Finally, the binding ability of the drug to the active components and potential targets were predicted using molecular docking.Results: S. miltiorrhizae-C. pilosula had 72 active components, 128 targets, 3,775 POF targets, and 106 common targets. The potential targets were mainly related to the biological processes of DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, transcription factor activity, steroid receptor activity, and hypoxia response. Further, the Kyoto Encyclopedia of Genes and Genomes enrichment pathways included PI3K-Akt signaling pathway, apoptosis, interleukin (IL)-17 signaling pathway, relaxin signaling pathway, and other biological pathways.Conclusion(s): S. miltiorrhiza-C. pilosula can inhibit ovarian granulosa cell apoptosis and improve ovarian hemodynamics through multiple targets and multiple pathways and help treat POF.