Encyclopedia Of Traditional Chinese Medicine Research Articles

Chemical functiomics: a new direction for modern research on traditional Chinese medicine--a case study of core component group of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs

To analyze the complex relationship between chemical components and functions of traditional Chinese medicine, this study put forward the concept of "chemical functiomics" for the first time and defined the connotation and significance of "chemical functiomics" based on the research on the core components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs, which provided a new direction for modern research on traditional Chinese medicine. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Encyclopedia of Traditional Chinese Medicine(ETCM), and Natural Product Activity and Species Source Database(NPASS) were searched for the chemical components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs included in the Science of Chinese Materia Medica with the names of the above drugs as the key words. The pharmacological actions corresponding to the functions of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs were standardized with MESH2021 terms(Chinese version) as the standard. Discovery Studio 4.5 was used to calculate absorption, distribution, metabolism, excretion, and toxicity(ADMET) molecular descriptors. Principal component analysis and 95% confidence ellipse calculation were carried out using Origin 2021. Hydrogenation of chemical components and Murcko skeleton calculation were completed using the CDK algorithm and the RDKit algorithm packages in the KNIME 4.3.2. The results showed that there were 404 common components of hemostatic drugs and blood-activating/stasis-resolving drugs, accounting for 17.3% of the total components. The plotted chemical function diagrams of hemostatic drugs and blood-activating/stasis-resolving drugs showed that the pharmacological action group acting as a bridge connected the function group and the chemical composition group, and different combinations of pharmacological effects indicated different functions. The unique Murcko skeleton of the core components of hemostatic drugs mainly included naphthoquinone and tetracyclic triterpenes, while those of blood-activating/stasis-resolving drugs were mainly alkaloids. Based on the research on the core components of hemostatic and blood-activating/stasis-resolving Chinese herbal drugs, this study provides references for the study of "chemical functiomics" and support for the research on the functional material basis of traditional Chinese medicine.

Pharmacodynamic mechanism of Tibetan medicine Liurui Capsules on experimental autoimmune uveitis in rats based on network pharmacology and animal experiments

By integrating network pharmacology and animal experiments, we studied the pharmacodynamic mechanism of the Tibetan medicine Liurui Capsules in the treatment of experimental autoimmune uveitis(EAU). The active ingredients and targets of Liurui Capsules were searched against the Encyclopedia of Traditional Chinese Medicine(ETCM), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM), and relevant literatures. The EAU-related targets were obtained from Gene Expression Omnibus(GEO), GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). The common targets shared by Liurui Capsules and EAU were identified, and the protein-protein interaction(PPI) network was established via STRING. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were conducted via g: Profiler. The rat model of EAU was induced by interphotoreceptor retinoid-binding protein(IRBP) and treated with Liurui Capsules. The inflammatory response of anterior segment and the pathological morphology of retina were observed. The mRNA and protein levels of delta-like ligand 4(DLL4), Notch1, interleukin-17(IL-17), and tumor necrosis factor-alpha(TNF-α) were determined by real-time quantitative PCR(q-PCR) and Western blot, respectively. The network pharmacology analysis predicted 51 common targets of Liurui Capsules and EAU, which were mainly involved in IL-17, TNF, and nuclear factor-kappa B(NF-κB) signaling pathways, as well as liposome receptors and other biological processes. Compared with the control group, the modeling of EAU caused inflammatory changes in the anterior segment and retina and up-regulated mRNA and protein levels of DLL4, Notch1, IL-17, and TNF-α in ocular tissue. Compared with the model group, Liurui Capsules reduced the inflammatory reaction of anterior segment and retina and down-regulated the mRNA and protein levels of DLL4, Notch1, IL-17, and TNF-α. Liurui Capsules can down-regulate the expression of the proteins involved in DLL4/Notch1/IL-17 signaling pathway in ocular tissue and alleviate the ocular inflammation, which may be one of the mechanisms of Liurui Capsules in the treatment of EAU.

Network pharmacology-based strategy to investigate pharmacological mechanism of Liuwei Dihuang Pill against postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) has became 1 of most prevalent bone disorders with aging population. Liuwei Dihuang (LWDH) Pill, a classical kidney-tonifying prescription, is extensively used to treat PMOP in China. The aim of this study is to explore the pharmacological mechanisms of LWDH Pill against PMOP via network pharmacological strategy. The active ingredients of LWDH Pill were screened out from the Traditional Chinese Medicine System Pharmacology, Encyclopedia of Traditional Chinese Medicine and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine Databases, and their related target genes were fished in the UniProt database. Simultaneously, the GeneCards and DisGeNET databases were used to identify the target genes of PMOP. Through establishing a protein-protein interaction network, the overlapping genes between LWDH Pill and PMOP were identified to analyze their interactions and the hub target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to predict the underlying biological processes (BP) and signaling pathways, respectively. A total of 64 active ingredients and 653 related target genes were identified in LWDH Pill, and 292 target genes were closely associated with PMOP. After matching the target genes between LWDH Pill and PMOP, 84 overlapping targets were obtained and considered as therapeutically relevant. Through construction of a protein-protein interaction network, we identified 20 hub target genes including IL6, INS, tumor necrosis factor, AKT1, vascular endothelial growth factor A, IGF1, TP53, IL1B, MMP9, JUN, LEP, CTNNB1, EGF, PTGS2, PPARG, CXCL8, IL10, CCL2, FOS and ESR1. Gene Ontology enrichment analysis suggested that LWDH Pill exerted anti-PMOP effects via regulating multiple BP including cell proliferation and apoptosis, oxidative stress, inflammation and angiogenesis. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, interleukin-17 (IL-17) pathway and FoxO pathway that might be involved in modulating the above BP. Through network pharmacological approach, we investigated the potential therapeutic mechanism of LWDH Pill against postmenopausal osteoporosis in a systemic perspective. These identified multi-targets and multi-pathways provide promising directions for further revealing more exact mechanisms.

Shuangyu Tiaozhi decoction alleviates non-alcoholic fatty liver disease by improving lipid deposition, insulin resistance, and inflammation in vitro and in vivo.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Our previous studies have found that Shuangyu Tiaozhi Decoction (SYTZD) could produce an improvement in NAFLD-related indicators, but the underlying mechanism associated with this improvement remains unclear. The study aimed to investigate the potential mechanism of SYTZD against NAFLD through network pharmacology and experimental verification. The components of SYTZD and SYTZD drug containing serum were analyzed using ultra-performance liquid chromatography to quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Active components and targets of SYTZD were screened by the traditional Chinese medical systems pharmacology (TCMSP) and encyclopedia of traditional Chinese medicine (ETCM) databases. NAFLD-related targets were collected from the GeneCards and DisGeNET databases. The component-disease targets were mapped to identify the common targets of SYTZD against NAFLD. Protein-protein interaction (PPI) network of the common targets was constructed for selecting the core targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets was performed using the database for annotation, visualization, and integrated discovery (DAVID) database. Furthermore, animal and cell models were constructed for validating the predictions of network pharmacology. Lipid accumulation, liver histopathology, insulin resistance, and core gene expression were measured by oil red O staining, hematoxylin and eosin staining, insulin tolerance test, real-time quantitative polymerase chain reaction, and Western blotting, respectively. Two components and 22 targets of SYTZD against NAFLD were identified by UPLC-Q/TOF-MS and relevant databases. PPI analysis found that ESR1, FASN, mTOR, HIF-1α, VEGFA, and GSK-3β might be the core targets of SYTZD against NAFLD, which were mainly enriched in the thyroid hormone pathway, insulin resistance pathway, HIF-1 pathway, mTOR pathway, and AMPK pathway. Experimental results revealed that SYTZD might exert multiple anti-NAFLD mechanisms, including improvements in lipid deposition, inflammation, and insulin resistance. SYTZD treatment led to decreases in the lipid profiles, hepatic enzyme levels, inflammatory cytokines, and homeostatic model assessment for insulin resistance (HOMA-IR). SYTZD treatment affected relative mRNA and protein levels associated with various pathways. Our findings reveal that SYTZD could alleviate NAFLD through a multi-component, multi-target, and multi-pathway mechanism of action.

Natural products for migraine: Data-mining analyses of Chinese Medicine classical literature

Background: Treatment effect of current pharmacotherapies for migraine is unsatisfying. Discovering new anti-migraine natural products and nutraceuticals from large collections of Chinese medicine classical literature may assist to address this gap. Methods: We conducted a comprehensive search in the Encyclopedia of Traditional Chinese Medicine (version 5.0) to obtain migraine-related citations, then screened and scored these citations to identify clinical management of migraine using oral herbal medicine in history. Information of formulae, herbs and symptoms were further extracted. After standardisation, these data were analysed using frequency analysis and the Apriori algorithm. Anti-migraine effects and mechanisms of actions of the main herbs and formula were summarised. Results: Among 614 eligible citations, the most frequently used formula was chuan xiong cha tiao san (CXCTS), and the most frequently used herb was chuan xiong. Dietary medicinal herbs including gan cao, bai zhi, bo he, tian ma and sheng jiang were identified. Strong associations were constructed among the herb ingredients of CXCTS formula. Symptoms of chronic duration and unilateral headache were closely related with herbs of chuan xiong, gan cao, fang feng, qiang huo and cha. Symptoms of vomiting and nausea were specifically related to herbs of sheng jiang and ban xia. Conclusion: The herb ingredients of CXCTS which presented anti-migraine effects with reliable evidence of anti-migraine actions can be selected as potential drug discovery candidates, while dietary medicinal herbs including sheng jiang, bo he, cha, bai zhi, tian ma, and gan cao can be further explored as nutraceuticals for migraine.

Ningmitai capsules have anti-inflammatory and pain-relieving effects in the chronic prostatitis/chronic pelvic pain syndrome mouse model through systemic immunity.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects the physical and mental health of approximately 90% of males. Due to its complex and unclear etiology, the treatment methods that are currently available for chronic prostatitis/chronic pelvic pain syndrome are controversial, and their efficacy is unsatisfactory. At present, most researchers believe that this kind of prostatitis is caused by autoimmune inflammation. Chinese herbs, which are the essence of traditional Chinese medicine (TCM), are emerging treatment options for inflammation and immune diseases. In this experiment, we investigated the effect of Ningmitai capsules (a kind of traditional Chinese medicine widely used to treat lower urinary tract inflammation and pain in males) on chronic prostatitis/chronic pelvic pain syndrome in a non-obese diabetes-experimental autoimmune prostatitis (NOD-EAP) mouse model. First, by using bioinformatics analysis of data from the Encyclopedia of Traditional Chinese Medicine (ETCM) database, we found that quercetin, which is one of the main components of Ningmitai capsules, could reduce the secretion of CCL2 by inhibiting the MAPK pathway. In animal experiments, it was found that after Ningmitai treatment, the inflammation in mouse prostates was alleviated, the expression of CCL2, which is related to pain, and MAPK pathway components were downregulated, and the activation of the inflammatory NF–κB and STAT3 pathways was reduced. Pelvic pain and inflammation were relieved in mice with EAP. Due to the presence of the blood–prostate barrier, the drug may not completely reach the prostate directly and take effect locally. However, we found that after Ningmitai treatment, the proportions of proinflammatory CD11b+Ly6Chigh immune cells in the spleen, bloodstream (systemic immunity), and prostate (local immunity) were reduced. The infiltration of CD11b+ immune cells into the spleen and prostate was decreased. These findings suggested that Ningmitai can treat chronic prostatitis/chronic pelvic pain syndrome by affecting systemic and local immunities through the CCL2–MAPK pathway.

Network Pharmacology and Molecular Docking to Explore the Mechanism of Kangxian Decoction for Epilepsy.

Purpose Kangxian decoction (KXD) has been used in clinical practice to treat epilepsy. The purpose of this study was to explore the active components of KXD and clarify its antiepileptic mechanism through network pharmacology and molecular docking. Methods The components of KXD were collected from the Encyclopedia of Traditional Chinese Medicine (ETCM) database and the literature was searched. Then, active ingredients were screened by SwissADME and potential targets were predicted by the SwissTargetPrediction database. Epilepsy-related differentially expressed genes were downloaded from the Gene Expression Omnibus database. A component-target-pathway network was constructed with Cytoscape. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein‒protein interaction network analysis revealed the potential mechanism and critical targets. Receiver operating characteristic (ROC) curves and box plots in microarray data validated the good diagnostic value and significant differential expression of these critical genes. Molecular docking verified the association between active ingredients and essential target proteins. Results In our study, we screened the important compounds of KXD for epilepsy, including quercetin, baicalin, kaempferol, yohimbine, geissoschizine methyl ether, baicalein, etc. KXD may exert its therapeutic effect on epilepsy through the following targets: PTGS2, MMP9, CXCL8, ERBB2, and ARG1, acting on the following pathways: neuroactive ligand-receptor interactions, arachidonic acid metabolism, IL-17, TNF, NF-kappa B, and MAPK signaling pathways. The molecular docking results showed that the active ingredients in KXD exhibited good binding ability to the key targets. Conclusion In this study, we explored the possibility that KXD for epilepsy may act on multiple targets through multiple active ingredients, involving neurotransmitters and neuroinflammatory pathways, providing a theoretical basis for subsequent clinical and experimental studies that will help develop effective new drugs to treat epilepsy.

Decoding the Mechanism of CheReCunJin Formula in Treating Sjögren's Syndrome Based on Network Pharmacology and Molecular Docking.

Background Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by progressive oral and ocular dryness that correlates poorly with autoimmune damage to the glands. CheReCunJin (CRCJ) formula is a prescription formulated according to the Chinese medicine theory for SS treatment. Objective This study aimed to explore the underlying mechanisms of CRCJ against SS. Methods The databases, including Traditional Chinese Medicine System Pharmacology, Encyclopedia of Traditional Chinese Medicine, Bioinformatics Analysis Tool for the molecular mechanism of Traditional Chinese Medicine, and Traditional Chinese Medicine Integrated Databases, obtained the active ingredients and predicted targets of CRCJ. Then, DrugBank, Therapeutic Target Database, Genecards, Comparative Toxicogenomics Database, and DisGeNET disease databases were used to screen the predicted targets of SS. Intersected targets of CRCJ and SS were visualized by using Venn diagrams. The overlapping targets were uploaded to the protein–protein interaction network analysis search tool. Cytoscape 3.8.2 software constructed a “compound-targets-disease” network. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses characterized potential targets' biological functions and pathways. AutoDock Vina 1.1.2 software was used to research and verify chemical effective drug components and critical targets. Results From the database, we identified 878 active components and 2578 targets of CRCJ, and 827 SS-related targets. 246 SS-related genes in CRCJ were identified by intersection analysis, and then ten hub genes were identified as crucial potential targets from PPI, including ALB, IL-6, TNF, INS, AKT1, IL1B, VEGFA, TP53, JUN, and TLR4. The process of CRCJ action against SS was mainly involved in human cytomegalovirus infection and Th17 cell differentiation, as well as the toll-like receptor signaling and p53 signaling pathways. Molecular docking showed that the bioactive compounds of CRCJ had a good binding affinity with hub targets. Conclusions The results showed that CRCJ could activate multiple pathways and treat SS through multiple compounds and targets. This study lays a foundation for better elucidation of the molecular mechanism of CRCJ in the treatment of SS, and also provides basic guidance for future research on Chinese herbal compounds.

Potential Targets and Action Mechanism of Gastrodin in the Treatment of Attention-Deficit/Hyperactivity Disorder: Bioinformatics and Network Pharmacology Analysis.

Objective Gastrodin is a main medicinal component of traditional Chinese medicine (TCM) Gastrodia elata Blume (G. elata), presenting the potential for the treatment of attention-deficit/hyperactivity disorder (ADHD). However, the underlying targets and action mechanisms of the treatment have not been identified. Methods The gastrodin-related microarray dataset GSE85871 was obtained from the GEO database and analyzed by GEO2R to obtain differentially expressed genes (DEGs). Subsequently, the targets of gastrodin were supplemented by the Encyclopedia of Traditional Chinese Medicine (ETCM), PubChem, STITCH, and SwissTargetPrediction databases. ADHD-associated genes were collected from six available disease databases (i.e., TTD, DrugBank, OMIM, PharmGKB, GAD, and KEGG DISEASE). The potential targets of gastrodin during ADHD treatment were obtained by mapping gastrodin-related targets with ADHD genes, and their protein–protein interaction (PPI) relationship was constructed by the STRING database. The GO function and KEGG pathway enrichment analyses were performed using the ClueGO plug-in in the Cytoscape software and DAVID database, respectively. Finally, the binding affinity between gastrodin and important targets was verified by molecular docking. Results A total of 460 gastrodin-related DEGs were identified from GSE85871, and 124 known gastrodin targets were supplemented from 4 databases, including ETCM. A total of 440 genes were collected from the above 6 disease databases, and 267 ADHD-relevant genes were obtained after duplicate removal. Through mapping the 584 gastrodin targets to the 267 ADHD genes, 16 potential therapeutic targets were obtained, among which the important ones were DRD2, DRD4, CHRNA3, CYP1A1, TNF, IL6, and KCNJ3. The enrichment analysis results indicated that 16 potential targets were involved in 25 biological processes (e.g., dopamine (DA) transport) and 22 molecular functions (e.g., postsynaptic neurotransmitter receptor activity), which were mainly localized at excitatory synapses. The neuroactive ligand-receptor interaction, cholinergic synapse, and dopaminergic synapse might be the core pathways of gastrodin in ADHD treatment. Through molecular docking, it was preliminarily verified that gastrodin showed good binding activity to seven important targets and formed stable binding conformations. Conclusions Gastrodin might exert an anti-ADHD effect by upgrading the dopaminergic system and central cholinergic system, inhibiting the inflammatory response and GIRK channel, and exerting a synergistic effect with other drugs on ADHD. For this reason, gastrodin should be considered a multitarget drug for ADHD treatment.

Network pharmacology study of Yishen capsules in the treatment of diabetic nephropathy.

ObjectiveIn this study, we used network pharmacology to explore the possible therapeutic mechanism underlying the treatment of diabetic nephropathy with Yishen capsules.MethodsThe active chemical constituents of Yishen capsules were acquired using the Traditional Chinese Medicine Systems Pharmacology platform and the Encyclopedia of Traditional Chinese Medicine. Component target proteins were then searched and screened in the BATMAN database. Target proteins were cross-validated using the Comparative Toxicogenomics Database, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the target proteins were performed. Then, protein–protein interaction (PPI) analysis was performed using the STRING database. Finally, a pharmacological network was constructed to show the component-target-pathway relationships. Molecular docking was used to analyse the interaction between drug components and target proteins.ResultsIn total, 285 active chemical components were found, including 85 intersection targets against DN. In the pharmacological network, 5 key herbs (A. membranaceus, A. sinensis, E. ferox, A. orientale, and R. rosea) and their corresponding 12 key components (beta-sitosterol, beta-carotene, stigmasterol, alisol B, mairin, quercetin, caffeic acid, 1-monolinolein, kaempferol, jaranol, formononetin, and calycosin) were screened. Furthermore, the 12 key components were related to 24 target protein nodes (e.g., AGT, AKT1, AKT2, BCL2, NFKB1, and SIRT1) and enriched in 24 pathway nodes (such as the NF-kappa B, AGE-RAGE, toll-like receptor, and relaxin signaling pathways). Molecular docking revealed that hydrogen bond was formed between drug components and target proteins.ConclusionIn conclusion, the active constituents of Yishen capsules modulate targets or signaling pathways in DN pathogenesis.

The Mechanism of Action of Qihuang Jiangtang Capsule in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking Technology

Abstract Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule (QHJTC) in the treatment of type 2 diabetes mellitus (T2DM) through network pharmacology and molecular docking. Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine. The targets related to the active components were obtained via PubChem database. The targets related to T2DM were retrieved through the GeneCards database. The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram, and the intersecting targets were the potential targets of QHJTC in treating T2DM. The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network, and the key compounds and targets were screened by the Network Analyzer module in the Tools module. The potential targets were imported into the STRING database to obtain the interaction relationships, so as to analyze and construct the protein–protein interaction (PPI) network by Cytoscape 3.7.2 software. The intersecting targets were introduced into Metascape for gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the “active component–important target-key pathway network ” for the intervention of T2DM with QHJTC. The molecular docking of active components and core targets was performed with AutoDock software. Results A total of 237 active components and 281 related targets were obtained from QHJTC, as well as 1 362 T2DM targets and 155 potential targets of QHJTC in treating T2DM. There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis. There were 471 terms obtained from GO functional enrichment analysis, among which 248 related to biological processes, 125 related to molecular functions, and 98 related to cellular components. There were 299 signaling pathways obtained from KEGG pathway enrichment analysis. The active components of QHJTC were found spontaneously binding to the core targets. Conclusions QHJTC can treat T2DM through multi-components, multi-targets, and multi-pathways.

Potential Mechanisms of Shu Gan Jie Yu Capsule in the Treatment of Mild to Moderate Depression Based on Systemic Pharmacology and Current Evidence.

Background Shu Gan Jie Yu (SGJY) capsule has a good effect on relieving depressive symptoms in China. However, the mechanism of action is still unclear. Therefore, systemic pharmacology and molecular docking approaches were used to clarify its corresponding antidepressant mechanisms. Methods Traditional Chinese Medicine Database and Analysis Platform (TCMSP), the Encyclopedia of Traditional Chinese Medicine (ETCM), and Swiss Target Prediction servers were used to screen and predict the bioactive components of the SGJY capsule and their antidepressive targets. Mild to moderate depression (MMD) related genes were obtained from GeneCards and DisGeNET databases. A network of bioactive components-therapeutic targets of the SGJY capsule was established by STRING 11.5 and Cytoscape 3.9.0 software. Gene function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by utilizing Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Active components were taken to dock with the hypothetical proteins by iGEMDOCK and SwissDock, and the docking details were visually displayed by UCSF Chimera software. Then, the related research literature of the SGJY capsule was reviewed, summarized, sorted, and analyzed, including experimental evidence and clinical experience. Results Seven active components and 45 intersection targets were included in the study. PPI network had genuinely uncovered the potential therapeutic targets, such as AKT1, HSP90AA1, ESR1, EGFR, and PTGS2. KEGG pathway analysis showed that the mechanism of the SGJY capsule on MMD was mainly involved in the PI3K-Akt signaling pathway. Conclusions In this study, we have successfully predicted the biochemically active constituents, potential therapeutic targets, and comprehensively predicted the related drug-gene interaction of the SGJY capsule for treating MMD and provided a basis for subsequent experiments.

Mechanism of action of Bu Zhong Yi Qi Decoction in the treatment of chronic fatigue syndrome based on network pharmacology and molecular docking

ObjectiveBu Zhong Yi Qi (BZYQ) decoction is a classic prescription in Chinese history that has an obvious effect on improving fatigue symptoms. The objective was to investigate the substance basis and mechanism of BZYQ in the treatment of chronic fatigue syndrome (CFS) at the molecular level based on network pharmacology and molecular docking technology. MethodThe active components and their targets of Huangqi, Baizhu, Renshen, Gancao, Danggui, Chaihu, Chenpi, Shenma in BZYQ were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database and the Encyclopedia of Traditional Chinese Medicine (ETCM). The UniProt database was used to calibrate the target information in BZYQ. CFS target genes were obtained from the GeneCards and DisGeNET databases. Cytoscape 3.7.2 software and the STRING 11.0 database were used to construct a protein–protein interaction (PPI) network and screen core targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Subsequently, the binding affinity of BZYQ with key target receptors was assessed by molecular docking analysis. ResultBZYQ consists of 329 active components, 198 targets, and 6490 CFS-related targets. There were 180 common targets of BZYQ and CFS, including nitric oxide synthase Ⅱ (NOS2), estrogen receptor beta (ESR2), interleukin-2 (IL2), interleukin-6 (IL6), interleukin-1 beta (IL1B), MAP kinase-activated protein kinase 3 (MAPK3), vascular endothelial growth factor A (VEGFA), nitric oxide synthase Ⅲ (NOS3), and matrix metallopeptidase 2 (MMP2). More than 600 GO terms were obtained (Biological Process 630; Cellular Component: 95; Molecular Function:152) and 185 related signaling pathways, involving the AGE-RAGE signaling pathway in diabetic complications, pathways in cancer, TNF signaling pathway, lipid and atherosclerosis, cAMP signaling pathway, VEGF signaling pathway, calcium signaling pathway, and NF-kappa B signaling pathway. ConclusionBZYQ achieves the purpose of treating CFS through the interaction mechanism of multiple components, multiple targets and multiple pathways. It advances the study of BZYQ to the clinical stage, expounds the effective mechanism of Traditional Chinese Medicine from an overall perspective, and provides ideas at the molecular level for future experimental study.

Integrating network pharmacology and molecular docking to explore the potential mechanism of Xinguan No. 3 in the treatment of COVID-19

Abstract Xinguan No. 3 has been recommended for the treatment of coronavirus disease 2019 (COVID-19); however, its potential mechanisms are unclear. This study aims to explore the mechanisms of Xinguan No. 3 against COVID-19 through network pharmacology and molecular docking. We first searched the ingredients of Xinguan No. 3 in three databases (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Traditional Chinese Medicines Integrated Database, and The Encyclopedia of Traditional Chinese Medicine). The active components and their potential targets were predicted through the SwissTargetPrediction website. The targets of COVID-19 can be found on the GeneCards website. Protein interaction analysis, screening of key targets, functional enrichment of key target genes, and signaling pathway analysis were performed through Search Tool for the Retrieval of Interacting Genes databases, Metascape databases, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases. Finally, the affinity of the key active components with the core targets was verified by molecular docking. The results showed that five core targets had been screened, including MAPK1, NF-κB1, RELA, AKT1, and MAPK14. Gene ontology enrichment analysis revealed that the key targets were associated with inflammatory responses and responses to external stimuli. KEGG enrichment analysis indicated that the main pathways were influenza A, hepatitis B, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and TNF signaling pathway. Therefore, Xinguan No. 3 might play a role in treating COVID-19 through anti-inflammatory, immune responses, and regulatory responses to external stimuli.

Prunella vulgaris L. - A Review of its Ethnopharmacology, Phytochemistry, Quality Control and Pharmacological Effects.

Prunella vulgaris L. (PVL) is dried fruit spike of Lamiacea plant Prunella vulgaris L., which is a perennial herb with medicinal and edible homology used for thousands of years. PVL is bitter, acrid, cold, and belongs to the liver and gallbladder meridians. It clears the liver and dissipate fire, improve vision, disperse swelling, and has satisfactory clinical therapeutic effects on many diseases such as photophobia, dizziness, scrofula, goiter, breast cancer. The collection of information and data related to PVL comes from literatures retrieved and collated from various online scientific databases (such as CNKI, VIP, PubMed, Web of Science, Research Gate, Science Database), ancient books of traditional chinese medicine (Encyclopedia of Traditional Chinese Medicine, Classics of Traditional Chinese Medicine, Dictionary of Traditional Chinese Medicine), and Doctoral and Master’s Dissertations. Currently, the major chemical constituents isolated and identified from PVL are triterpenoids, steroids, flavonoids, phenylpropanoids, organic acids, volatile oils and polysaccharides. Modern pharmacological studies have shown that PVL has a wide range of pharmacological activities, including anti-inflammatory, anti-tumor, antibacterial and antiviral effects, as well as immune regulation, antihypertensive, hypoglycemic, lipid-lowering, antioxidant, free radical scavenging, liver protection, sedative and hypnotic effects. This paper reviewes the botany, ethnopharmacology, traditional application, phytochemistry, analytical methods, quality control, pharmacological effects of PVL. It can be used not only as medicine, but also gradually integrated into the “medicine and food homology” and “Chinese medicine health” boom. More importantly, it has great potential for drug resources development. This paper deeply discusses the shortcomings of current PVL research, and proposes corresponding solutions, in order to find a breakthrough point for PVL research in the future. At the same time, it is necessary to further strengthen the research on its medicinal chemistry, mechanism of action and clinical application efficacy in the future, and strive to extract, purify and synthesize effective components with high efficiency and low toxicity, so as to improve the safety and rationality of clinical medication.

Network pharmacology and molecular docking analysis on molecular targets and mechanism prediction of Huanglian Jiedu Decoction in the treatment of COVID-19

ObjectiveTo investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction (黄连解毒汤, HLJDD) in the treatment of Corona Virus Disease 2019 (COVID-19) through network pharmacology and molecular docking analysis. MethodsThe chemical constituents and action targets of HLJDD were retrieved on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SymMap v2, Encyclopedia of Traditional Chinese Medicine (ETCM), a High-throughput Experiment- and Reference-guided Database of Traditional Chinese Medicine (HERB), and Traditional Chinese Medicine Integrated Database (TCMID). UniProt and GeneCards were used to query the target genes that corresponding to the active compounds, and then a compound-target network was constructed using Cytoscape 3.7.2. Gene Ontology (GO) database was used to annotate GO functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to predict the possible mechanisms of active compounds. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to analysis the tissue enrichment. The main active compounds in HLJDD are molecularly docked with their corresponding related targets. ResultsSeventy-six compounds were screened and 458 corresponding targets in the network were obtained. Gene annotation showed that the targets were involved mainly in 1953 biological processes. 884 signaling pathways was enriched, involving signaling by interleukins, cytokine signaling in immune system, generic transcription pathway, and RNA polymerase II transcription. The targets mainly distributed in the lung, liver, and placenta, involving a variety of immune cells, such as T cells and B cells. The molecular docking results showed that core compounds such as wogonin, berberine, and baicalein had high affinity with tumor necrosis factor (TNF), insulin (INS), and tumor protein 53 (TP53). ConclusionThe active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A (VEGFA), INS, interleukin-6 (IL-6), TNF, caspase-3 , TP53, and mitogen-activated protein kinase 3 (MAPK3).

The Pharmacological Mechanism of the Effect of Plant Extract Compound Drugs on Cancer Pain Based on Network Pharmacology.

Objective We systematically analyzed the mechanism of plant-derived drugs alleviating cancer pain in our hospital through network pharmacology, so as to provide the possibility of further application of traditional Chinese medicine in the treatment of cancer pain. Methods We used TCMSP, ETCM, and TCMID databases to mine the active ingredients of plant-derived drugs. We combined OMIM, GeneCards, and DrugBank databases to mine and match the common targets of plant-derived drugs for cancer pain. We used the STRING platform and Cytoscape software to analyze and screen out the core targets. We used GO and KEGG methods to analyze the biological processes, molecular functions, cellular composition, and signaling pathways involved in the reduction of cancer pain by plant-derived drugs. Results We found 153 active ingredients from botanical drugs by TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, TCMSP), ETCM (The Encyclopedia of Traditional Chinese Medicine), and TCMID (Traditional Chinese Medicine Integrated Database) databases, covering 341 protein targets in human body. Combined with OMIM (Online Mendelian Inheritance in Man), GeneCards, and DrugBank databases, we excavated and matched 141 targets of plant-derived drugs and cancerous pain diseases. Through the analysis of the STRING platform and Cytoscape software, 19 core targets including TNF, MAPK1, JUN, and IL-6 were screened out. Go and KEGG enrichment showed that plant-derived drugs alleviated cancer pain processes involving 193 biological processes, 47 molecular functions, 22 cell components, and 118 signaling pathways. By screening genes involved in KEGG signaling pathway, it was found that plant-derived drugs were mainly associated with PI3K-Akt signaling pathway, tumor necrosis factor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway in alleviating cancer pain. Conclusion These results indicate that botanical drugs can positively affect the expression of inflammatory factors and apoptotic factors in the process of treatment and relief of cancer pain, which is expected to have a potential therapeutic effect on the relief of cancer pain.

Molecular mechanism and therapeutic potential of YiQi FuMai injection in acute heart failure

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The National Science Foundation for Distinguished Young Scholars of China Background Acute heart failure (AHF) is a significant public health problem related to the high mortality and rehospitalization rate of patients. Although drug development is never interrupted, no single drug has been proven to play a decisive role in improving the survival of AHF patients. In China, multi-component traditional Chinese medicine has been widely used to treat AHF. As a Chinese herbal injection included in medical insurance, Yiqi Fumai Injection can reduce the level of NT-proBNP in AHF patients, improve heart function, and alleviate symptoms and signs related to heart failure. To further evaluate the therapeutic effect of Yiqi Fumai Injection on AHF, a multi-center, double-blind, randomized controlled trial that intends to recruit 1270 patients is being carried out in China. However, the mechanism of Yiqi Fumai Injection in the treatment of AHF has not been clarified. To further explore the underlying mechanism, we used systematic pharmacology methods to explore the potential molecular mechanisms of biologically active compounds. Methods We used the databases of HERB, the Encyclopedia of Traditional Chinese Medicine (ETCM), the Comparative Toxicogenomics Database (CTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards to predict the active ingredients and potential targets of Yiqi Fumai Injection in the treatment of AHF. STRING was used for PPI network construction and analysis. Cytoscape was used to build a network between Chinese medicine, ingredients and targets. The DAVID, GO, and KEGG databases were used to predict the potential pathways of Yiqi Fumai Injection for the treatment of AHF. Results We obtained 31 active compounds of Yiqi Fumai Injection from HERB and ECTM databases. By overlapping targets between YQFMI and AHF, a total of 240 potential targets for Yiqi Fumai Injection to treat AHF were selected. According to the H-C-T network topology analysis, the core compounds include beta-sitosterol, Uridine, Guanosine, and Stigmasterol. Sixteen protein targets had significantly higher node degrees than the average in the PPI network, including AKT1, JUN, TNF, EDN1, CASP3, ESR1, DLG4, PTGS2, NOS3, IL1B, C3, AR, LEP, CNR1, CHRM2, and DRD2. The PPI results showed that the potential therapeutic targets of YQFMI were densely enriched in pathways related to endothelial function, neuromodulation, and lipid metabolism.The same results were shown in GO and KEGG pathway enrichment. Conclusion Our results indicate that Yiqi Fumai Injection may achieve the goal of improving AHF-related symptoms by regulating the function of vascular endothelium and nerves and the biosynthetic pathway of lipid metabolism. These findings support previous studies and provide a reference for studying the mechanism of Yiqi Fumai Injection in the treatment of AHF. Abstract Figure.

Study on alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury based on network pharmacology and cell experiments

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.

Chinese Pharmacopoeia Revisited: A Review of Anti-Depression Herbal Sources

Depression, which can be accompanied by many fatal diseases and a low life quality, has become the leading cause of ill health and disability worldwide. However, Chinese Pharmacopoeia, the most authoritative and evidence-based encyclopedia of Traditional Chinese Medicine (TCM), could contain leads and insights into the development of new antidepressant drugs. In this work, nine herbal medicines with ‘dispel melancholy functions’ specifically documented in Chinese Pharmacopoeia have been comprehensively reviewed with respect to clinical trials, and phytochemical and pharmacological aspects. The nine drugs are Rosae Chinensis Flos, Croci Stigma, Albiziae Cortex and Flos, Roase Rugosae Flos, Curcumae Radix, Hyperici Perforati Herba, Cyperi Rhizoma and Bupleuri Radix. The mechanisms of action of their functional antidepressant compounds, including gallic acid, hypericin, kaempferol, crocetin, crocin, quercetin, luteolin, isorhamnetin, curcumin, hyperforin, adhyperforin, catechin, rutin, puerarin, and saikosaponins A and D, have been collected and discussed. These traditional Chinese herbs and their active compounds provide a promising resource to develop effective new antidepressant drugs in future. Moreover, mechanistic investigations, safety verification and large-scale clinical trials are still expected to finally transform such TCM-based antidepressant resources to new drugs for patients suffering from depression.