Traditional Chinese Medicine Database Research Articles

TCMSID: a simplified integrated database for drug discovery from traditional chinese medicine

Traditional Chinese Medicine (TCM) has been widely used in the treatment of various diseases for millennia. In the modernization process of TCM, TCM ingredient databases are playing more and more important roles. However, most of the existing TCM ingredient databases do not provide simplification function for extracting key ingredients in each herb or formula, which hinders the research on the mechanism of actions of the ingredients in TCM databases. The lack of quality control and standardization of the data in most of these existing databases is also a prominent disadvantage. Therefore, we developed a Traditional Chinese Medicine Simplified Integrated Database (TCMSID) with high storage, high quality and standardization. The database includes 499 herbs registered in the Chinese pharmacopeia with 20,015 ingredients, 3270 targets as well as corresponding detailed information. TCMSID is not only a database of herbal ingredients, but also a TCM simplification platform. Key ingredients from TCM herbs are available to be screened out and regarded as representatives to explore the mechanism of TCM herbs by implementing multi-tool target prediction and multilevel network construction. TCMSID provides abundant data sources and analysis platforms for TCM simplification and drug discovery, which is expected to promote modernization and internationalization of TCM and enhance its international status in the future. TCMSID is freely available at https://tcm.scbdd.com.

Feasibility and mechanism analysis of Reduning in the prevention of sepsis-induced pulmonary fibrosis.

Introduction: The increasing mortality in patients with sepsis-induced pulmonary fibrosis owes to a lack of effective treatment options. This study aims to explore the possibility and possible targets of Reduning in the prevention of sepsis-related pulmonary fibrosis. Methods: The active components and targets of Reduning were searched and screened from the database and analysis platform of traditional Chinese medicine (TCM) system pharmacology. GeneCards, human genome database, DisGeNET database, and the OMIM database were checked to determine the targets associated with sepsis-induced pulmonary fibrosis. DAVID Bioinformatics Resources 6.8 was used for GO and KEGG enrichment analysis to predict its possible signaling pathways and explore its molecular mechanism. The protein-protein interaction (PPI) network was used to identify key active components and core targets. Molecular docking technology was applied to screen the complexes with stable binding of key active components and core targets. Molecular dynamics simulations were used to verify the binding stability and molecular dynamics characteristics of the complexes. The protective effect of RDN on sepsis-induced pulmonary fibrosis was verified by in vitro and in vivo experiments. Results: There were 319 shared targets between sepsis-induced pulmonary fibrosis and RDN. GO enrichment analysis showed that they mainly regulated and participated in the positive regulation of kinase activity, mitogen-activated protein kinase (MAPK) cascade, and protein phosphorylation. KEGG enrichment analysis showed that they were mainly enriched in the mitogen-activated protein kinase cascade signaling pathway, the calcium signaling pathway, the apoptosis pathway, and other signaling pathways. The results of molecular docking and molecular dynamics simulations showed that the active components, stigmasterol, beta-sitosterol, and quercetin, had good binding activities with ERBB2, and they exhibited good stability. Molecular validation experiments confirmed RDN could alleviate lung fibrosis induced by cecum ligation and puncture (CLP), in parallel with the inhibition of the ERBB2-p38 MAPK pathway in mouse alveolar macrophages (AMs). Discussion: Reduning may prevent sepsis-induced pulmonary fibrosis by regulating the ERBB2-p38 MAPK signaling pathway, which provides a possibility for the prevention of sepsis-induced pulmonary fibrosis with traditional Chinese medicine.

Stimulation of hair growth by Tianma Gouteng decoction: Identifying mechanisms based on chemical analysis, systems biology approach, and experimental evaluation.

Hair serves important physiological functions, including temperature regulation and scalp protection. However, excessive shedding not only impacts these functions but can also significantly affect mental health and quality of life. Tianma Gouteng decoction (TGD) is a traditional Chinese medicine used for the treatment of various conditions, including hair loss. However, the associated mechanism underlying its anti-alopecia effect remains unknown. Therefore, this study aims to elucidate these mechanisms by employing systematic biology approaches, as well as in vitro and in vivo experimental validation. The chemical constituents of Tianma Gouteng decoction were identified using UHPLC-MS/MS, from which 39 potential bioactive components were screened, while an additional 131 putative Tianma Gouteng decoction beneficial components were extracted from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database. We then applied a dual-dimensional network pharmacology approach to analyze the data, followed by validation studies combining molecular docking techniques with in vivo and in vitro experiments. From the 39 bioactive components, including quercetin, luteolin, fisetin, wogonin, oroxylin A, boldine, tetrahydroalstonine, and galangin A, 782 corresponding targets were identified. In particular, GSK3β and β-catenin exhibited strong binding activity with the bioactive compounds. Hence, construction of a bioactive component-target network revealed that the mechanism underlying the anti-alopecia mechanism of Tianma Gouteng decoction primarily involved the Wnt/β-catenin signaling pathway. Moreover, C57BL/6J mice exhibited measurable improvements in hair follicle regeneration following treatment with Tianma Gouteng decoction. Additionally, β-catenin and p-GSK3β levels were upregulated, while GSK3β was downregulated in Tianma Gouteng decoction-treated animals and dermal papilla cells compared to control group. These in vivo and in vitro outcomes validated the targets and pathways predicted in the network pharmacology analysis of Tianma Gouteng decoction. This study provides a systematic analysis approach to identify the underlying anti-alopecia mechanisms of Tianma Gouteng decoction, further providing theoretical support for clinical assessment of Tianma Gouteng decoction.

Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation.

To explore the specific pharmacological molecular mechanisms of Kai Xin San (KXS) on treating Alzheimer's disease (AD) based on network pharmacology and experimental validation. The chemical compounds of KXS and their corresponding targets were screened using the Encyclopedia of Traditional Chinese Medicine (ETCM) database. AD-related target proteins were obtained from MalaCards database and DisGeNET databases. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis. Functional enrichment analysis predicted the potential key signaling pathways involved in the treatment of AD with KXS. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, the predicted key signaling pathway was validated experimentally. Positioning navigation and space search experiments were conducted to evaluate the cognitive improvement effect of KXS on AD rats. Western blot was used to further examine and investigate the expression of the key target proteins related to the predicted pathway. In total, 38 active compounds and 469 corresponding targets of KXS were screened, and 264 target proteins associated with AD were identified. The compound-target-disease and PPI networks identified key active ingredients and protein targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested a potential effect of KXS in the treatment of AD via the amyloid beta (A β)-glycogen synthase kinase-3 beta (GSK3 β)-Tau pathway. Molecular docking revealed a high binding affinity between the key ingredients and targets. In vivo, KXS treatment significantly improved cognitive deficits in AD rats induced by Aβ1-42, decreased the levels of Aβ, p-GSK3β, p-Tau and cyclin-dependent kinase 5, and increased the expressions of protein phosphatase 1 alpha (PP1A) and PP2A (P<0.05 or P<0.01). KXS exerted neuroprotective effects by regulating the Aβ -GSK3β-Tau signaling pathway, which provides novel insights into the therapeutic mechanism of KXS and a feasible pharmacological strategy for the treatment of AD.

Network-based pharmacology and molecular docking exploring the "Bupleuri Radix-Scutellariae Radix" mechanism of action in the viral hepatitis B treatment.

Viral hepatitis B is caused by the hepatitis B virus, which is characterized by liver lesions. Bupleuri Radix and Scutellariae Radix are the main traditional medicine pairs with remarkable efficacy in hepatitis B. However, their molecular mechanisms are incompletely understood. The main active components of Bupleuri Radix and Scutellariae Radix, as well as therapeutic targets for the treatment of hepatitis B, were identified through network pharmacology techniques. We identified viral hepatitis B targets using the GeneCards, online mendelian inheritance in man, and therapeutic target databases. We discovered the active components of Bupleuri Radix and Scutellariae Radix as well as therapeutic targets using the encyclopedia of traditional Chinese medicine, HERB, traditional Chinese medicine systems pharmacology database, and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. VENNY obtained the intersections. Cytoscape and STRING were used to create the "active ingredient-potential target" network and protein interaction network. The DAVID database was used to enrich GO and KEGG pathways. The results were confirmed using the molecular docking method. There were 1827 viral hepatitis B targets, and 37 active ingredients for Bupleuri and Scutellariae Radix, with the main components being quercetin, wogonin, baicalein, and kaempferol. Tumor necrosis factor (TNF), mitogen-activated protein kinase 3 (MAPK3), interleukin-6 (IL-6), vascular endothelial growth factor A, cysteinyl aspartate specific proteinase 3, transcription factor AP-1 (JUN), RAC-alpha serine/threonine-protein kinase, and cellular tumor antigen p53 are among the 78 common targets of Bupleuri Radix and Scutellariae Radix intervention in viral hepatitis B. KEGG enrichment resulted in 107 pathways, including cancer, hepatitis B, and TNF signaling pathways. According to the molecular docking technique, quercetin, wogonin, baicalein, and kaempferol had strong binding activities with TNF, MAPK3, and IL-6. In this study, we initially identified various molecular targets and multiple pathways involved in hepatitis B treatment with Bupleuri Radix and Scutellariae Radix.

Mechanisms of Semen Cassiae to Treat Hypercholesterolemia Based on Molecular Docking

Hypercholesterolemia is a major risk factor of cardiovascular disease with high prevalence rate. Studies have shown that the traditional Chinese medicine: Semen Cassiae can reduce blood cholesterol and lipids, but the functional components and molecular mechanisms need further elucidation. In this study, molecular docking technology is used to explore the mechanism of Semen Cassiae in the treatment of hypercholesterolemia. A total 88 active ingredients and 196 isomers of Semen Cassiae were obtained from the traditional Chinese medicine database: HERB. 6 hypercholesterolemia-related drug targets: proprotein convertase subtilisin/kexin type 9 (PCSK9), thyroid Hormone Receptor β (THRB), peroxisome proliferator-activated receptors (PPARd), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), insulin receptor (IR) and squalene monooxygenase (SQLE) were obtained from the Therapeutic Target Database. After data preprocessing, molecular docking analysis was conducted using the LibDock tool in Discovery Studio software, and the main “active ingredient-target” combinations with high scores were screened. The structure results showed high binding affinity of the active ingredients to the hypercholesterolemia-related targets. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed the involved pathways, including cholesterol and lipid metabolism, lipoprotein particle formation, cholesterol and lipid transfer and lipoprotein particle receptor binding processes. This study revealed that the anti-hypercholesterolemia activity of Semen Cassiae is a multicomponent, multitarget, and multipathway effects, and provides evidence for further development the clinical application value of Semen Cassiae on hypercholesterolemia.

Anti-COVID-19 Traditional Chinese Medicine Database

Background: Novel coronavirus pneumonia COVID-19 has become a serious threat to human health. Traditional Chinese Medicine (TCM) has a good clinical effect in the treatment of COVID-19, with a high effective rate and a low rate of turning to the serious stage. Objective: We generated the web-accessed anti-COVID-19 TCM database to provide the anti-COVID-19 TCM information to develop effective drugs for the treatment of COVID-19. Methods: Herein, we collected these prescriptions data by querying the CNKI and Wanfang Chinese databases, the clinical guidance for COVID-19 pneumonia diagnosis and treatment, and further set up the web-accessible anti-COVID-19 TCM database. Results: Altogether, 293 different prescriptions are applied in four different COVID-19 stages of treatment, and the prevention of COVID-19 is composed of 452 TCM components. Conclusion: The database provides comprehensive information for anti-COVID TCM and thus would help to investigate novel ways to develop new anti-COVID-19 agents.

Multi-omics approaches for in-depth understanding of therapeutic mechanism for Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) is extensively utilized in clinical practice due to its therapeutic and preventative treatments for various diseases. With the development of high-throughput sequencing and systems biology, TCM research was transformed from traditional experiment-based approaches to a combination of experiment-based and omics-based approaches. Numerous academics have explored the therapeutic mechanism of TCM formula by omics approaches, shifting TCM research from the "one-target, one-drug" to "multi-targets, multi-components" paradigm, which has greatly boosted the digitalization and internationalization of TCM. In this review, we concentrated on multi-omics approaches in principles and applications to gain a better understanding of TCM formulas against various diseases from several aspects. We first summarized frequently used TCM quality assessment methods, and suggested that incorporating both chemical and biological ingredients analytical methods could lead to a more comprehensive assessment of TCM. Secondly, we emphasized the significance of multi-omics approaches in deciphering the therapeutic mechanism of TCM formulas. Thirdly, we focused on TCM network analysis, which plays a vital role in TCM-diseases interaction, and serves for new drug discovery. Finally, as an essential source for storing multi-omics data, we evaluated and compared several TCM databases in terms of completeness and reliability. In summary, multi-omics approaches have infiltrated many aspects of TCM research. With the accumulation of omics data and data-mining resources, deeper understandings of the therapeutic mechanism of TCM have been acquired or will be gained in the future.

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.

Exploration of potential targets and mechanisms of Naringenin in treating autism spectrum disorder via network pharmacology and molecular docking.

Naringenin (NR) is a kind of flavonoid which plays a great role in the treatment of autism spectrum disorder (ASD). However, the underlying mechanism of NR in treating ASD still remains unclear. This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of NR on ASD. Targets related to NR were screened from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Encyclopedia of Traditional Chinese Medicine Database (ETCM), Traditional Chinese Medicine Integrated Database (TCMID), PharmaMapper database, and targets related to ASD were screened from Online Mendelian Inheritance In Man (OMIM), Disgenet, GeneCards, Therapeutic Target Database (TTD), Drugbank, and ETCM. Screened of the intersected gene targets. Then, we used the protein-protein interaction (PPI) networks to construct a PPI network and used Network Analyzer plug-in to perform topological analysis to screen out the core target. We used Metascape platform to perform gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and used Chem draw, Pymol, AutoDock 1.5.6 software for molecular docking verification with core targets. A total of 149 targets of NR and 1594 potential targets of ASD were screened, and 43 intersected targets and 8 key targets were obtained and screened. A total of 176 GO items were obtained by GO enrichment analysis (P < .05), 153 entries on biological process (BP), 12 entries on BP and 11entries on cell composition (CC) were included. A total of 100 signaling pathways were obtained by KEGG pathway enrichment screening (P < .05).The pathways that are closely related to the pathogenesis of ASD are estrogen signaling, thyroid hormone signaling pathway, prolactin signaling pathway, and endocrine resistance pathway. Molecular docking results showed that NR had the best docking activity with the core target CASP3, and had good binding ability with AKT1, ESR1, ACTB and MAPK3. Taken together, our findings support that NR exerts therapeutic effects on ASD with multi-target, and multi-pathway characteristics, which provides a preliminary theoretical basis for clinical trials. The mechanism of anti-oxidative stress response, anti-apoptosis, regulation of cell growth and metabolism, anti-inflammatory, balance hormone levels may be important for the therapeutic effect.

Identification of Taohong Siwu Decoction in Treating Chronic Glomerulonephritis Using Network Pharmacology and Molecular Docking

Background: Based on network pharmacology and molecular docking technology, the pharmacological mechanism of Taohong Siwu Decoction (THSWD) in the treatment of chronic glomerulonephritis (CGN) was analyzed to provide a theoretical basis for the subsequent development of new drugs and the clinical application of Traditional Chinese Medicine (TCM). Methods: Active ingredients of drugs and disease target genes were obtained from Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database and GeneCards database. The “drug component target” network of THSWD was constructed using Cytoscape version 3.8.2 software. The protein interaction was analyzed using STRING platform, the protein–protein interaction (PPI) network was constructed, and the potential protein function modules in the network were mined. Metascape platform was used to analyze “drug component target” and its biological processes and pathways. The clusterProfiler R package was called to perform kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) function enrichment analysis on CGN-related targets regulated by THSWD. Molecular docking verification was performed by AutoDock Vina software. Results: THSWD has 205 target genes and 45 active components, 104 of which are cross with the CGN inflammatory gene. Its main active ingredients, stigmasterol, kaempferol, and sitosterol, have positive relationships with the inflammatory targets of CGN, tumor necrosis factor (TNF), IL-6, AKT1, and MAPK14. THSWD modulates the biological pathway of CGN and mainly acts on TNF-α signal pathway, interleukin-17 signal pathway, etc., whose main functions are response to lipid sugar, heme binding, G protein-coupled amine receptor activity, etc. The results of molecular docking showed that the main active compounds could bind to the core targets and showed good affinity. Conclusion: The molecular mechanism of THSWD in the treatment of CGN from the perspective of network pharmacology are components such as beta-sitosterol, kaempferol, and quercetin and key action targets such as TNF, IL-6, AKT1 protein kinase, and MAPK14 protein kinase play a synergistic role in autoimmune, infection, and inflammatory response-related pathways.

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.

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.

Accuracy of reverse-transcription polymerase chain reaction and loop-mediated isothermal amplification in diagnosing severe fever with thrombocytopenia syndrome: A systematic review and meta-analysis.

Nucleic acid molecular diagnostic technology plays an important role in the detection of severe fever with thrombocytopenia syndrome (SFTS). However, no relevant reports have been published on the accuracy of reverse-transcription polymerase chain reaction (RT-PCR) and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) in the diagnosis of SFTS. Thus, we conducted a meta-analysis and systematic review to evaluate the accuracy of the two methods. On June 19, 2022, we comprehensively searched the PubMed, Embase, Cochrane Library, Web of Science, Scoups, Ovid, Proquest, China National Knowledge Infrastructure Database, Wan Fang Data, Traditional Chinese Medicine Database (Sinomed), VIP Database, and Reading Showing Database for articles on nucleic acid diagnostic techniques, such as RT-PCR and RT-LAMP, used to diagnose SFTS. Statistical analysis was performed using STATA 14.0 and Meta-Disc 1.4. Sixteen articles involving 2942 clinical blood samples were included in the analysis. RT-PCR and RT-LAMP were used as index tests, whereas RT-PCR or other detection methods were used as reference standards. The pooled values for the sensitivity, specificity, positive and negative likelihood ratios of the RT-PCR test were 0.97 (95% confidence interval [CI]: 0.92-0.99), 1.00 (95% CI: 0.98-1.00), 483.87 (95% CI: 58.04-4033.76), and 0.03 (95% CI:0.01-0.08), respectively. Those for the RT-LAMP test were 0.95 (95% CI: 0.91-0.97), 0.99 (95% CI: 0.93-1.00), 111.18 (95% CI: 13.96-885.27), and 0.05 (95% CI: 0.03-0.09), respectively. Both RT-PCR and RT-LAMP have high diagnostic value in SFTS and can be applied in different scenarios for laboratory confirmation or on-site screening.

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.

Network-Based Pharmacological Study on the Mechanism of Action of Buxue Liqi Huatan Decoction in the Treatment of Lung Cancer.

Objective This study aimed to investigate the mechanism of action of Buxue Liqi Huatan decoction against lung cancer through network pharmacology. Methods The chemical composition and targets of all the drugs in the Buxue Liqi Huatan decoction were obtained through the Database and Systematic Analysis Platform of Traditional Chinese Medicine Pharmacology, the Integrated Database of Traditional Chinese Medicine, and by screening lung cancer targets with the gene map and OMIM database. The targets were then imported into Cytoscape 3.7.2 to build a target network of active ingredients and imported into the STRING database to build a protein-protein interaction network. The BisoGenet plug-in in Cytoscape 3.7.2 was used for network topology analysis. Genetic ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analysis were performed on potential targets of the Buxue Liqi Huatan decoction for lung cancer using the R-language Bioconductor platform, and results were imported from Cytoscape 3.7.2 to obtain the KEGG network connection diagram via the Autodock molecular docking software. Results A total of 238 chemical components and 694 disease targets were obtained, including 133 intersecting targets. The key targets included TP53, AKT1, and MYC, and the GO functional analysis was mainly related to oxidative and cellular oxidative stress, apoptotic signaling, and antibiotic response. The results showed that the key target with the best binding performance was TP53. Conclusion The treatment of lung cancer with blood-supplementing, qi-transforming, and phlegm-transforming soups works through multiple components and targets. The active ingredients include quercetin, luteolin, naringenin, and baicalein. Among them, the core proteins of PPI protein interaction mainly include TP53, AKT1, MYC, EGRF, CCNB1, and ESR1. The enrichment analysis results show that the TNF signal pathway, PI3K-Akt signal pathway, AGE-RAGE, IL-17, etc., are the main signal pathways of Buxue Liqi Huatan decoction in treating lung cancer. This lays the foundation for further study of its mechanism.

Targeting Glutaminase by Natural Compounds: Structure-Based Virtual Screening and Molecular Dynamics Simulation Approach to Suppress Cancer Progression.

Cancer cells change their glucose and glutamine (GLU) metabolism to obtain the energy required to continue growing. Glutaminase (GLS) plays a crucial role in promoting cell metabolism for cancer cell growth; targeting GLU metabolism by inhibiting GLS has attracted interest as a potential cancer management strategy. Herein, we employed a sequential screening of traditional Chinese medicine (TCM) database followed by drug-likeness and molecular dynamics simulations against the active site of GLS. We report 12 potent compounds after screening the TCM database against GLS, followed by a drug-likeness filter with Lipinski and Veber rule criteria. Among them, ZINC03978829 and ZINC32296657 were found to have higher binding energy (BE) values than the control compound 6-Diazo-5-Oxo-L-Norleucine, with BEs of −9.3 and −9.7 kcal/mol, respectively, compared to the BE of 6-Diazo-5-Oxo-L-Norleucine (−4.7 kcal/mol) with GLS. Molecular dynamics simulations were used to evaluate the results further, and a 100 ns MD simulation revealed that the hits form stable complexes with GLS and formed 2–5 hydrogen bond interactions. This study indicates that these hits might be employed as GLS inhibitors in the battle against cancer. However, more laboratory tests are a prerequisite to optimize them as GLS inhibitors.

Molecular Mechanism of Xingnao Kaiqiao Pill for Perioperative Neurocognitive Disorder and Its Correlation With Immune and Inflammatory Signaling Pathways Based on Network Pharmacology and Molecular Docking.

To investigate the molecular mechanism of Xingnao Kaiqiao Pill in the treatment of perioperative neurocognitive disorder (PND) from the perspective of network pharmacology and molecular docking technology. Active ingredients of Xingnao Kaiqiao Pill were screened from the traditional Chinese medicine database and analysis platform, and the putative targets were predicted. The GeneCards database was searched to obtain PND-related targets. The genes corresponding to the targets were searched and annotated on the UniProt database. The VennDiagram package in R was employed to obtain common target genes. The overlap genes were introduced into STRING to obtain a protein-protein interaction (PPI) network; thus, key targets were screened. The target relationship network of “Xingnao Kaiqiao Pill–traditional Chinese medicine–compound–common target” was constructed by Cytoscape software. Using R language package Bioconductor, Gene Ontology (GO) and pathway enrichment analysis (Kyoto Encyclopedia of Genes and Genomes Pathway, KEGG Pathway) were performed on the common target genes. A total of 45 active ingredients of Xingnao Kaiqiao Pill were screened, with 182 potential targets, and 1,579 PND-related targets were retrieved from the GeneCards databases (Score ≥ 1). Using VennDiagram, 132 overlap genes were gotten. Xingnao Kaiqiao Pill mainly acted on targets, such as MAPK and JUN. GO enrichment analysis displayed G protein-coupled amine receptor activity, nuclear receptor activity, ligand-activated transcription factor activity, G protein-coupled neurotransmitter receptor activity, steroid hormone receptor activity, and cytokine receptor activity. KEGG enrichment analysis exhibited 157 signaling pathways. The regulation of interleukin 17, tumor necrosis factor, hypoxia-inducible factor-1, and MAPK signaling pathways affected central nervous system (CNS) inflammatory response, cellular immunity, tumor-related signaling pathways, protected neurons, and inhibited PND. The active ingredients of Xingnao Kaiqiao Pill adjust interleukin 17, tumor necrosis factor, hypoxia-inducible factor-1, and MAPK signaling pathways by acting on cell targets, such as JUN, MAPK, AKT1, etc., and finally exert a therapeutic effect on PND.