Encyclopedia Of Traditional Chinese Medicine Research Articles

Therapeutic Effects of Zanthoxyli Pericarpium on Intestinal Inflammation and Network Pharmacological Mechanism Analysis in a Dextran Sodium Sulfate-Induced Colitis Mouse Model.

(1) Background: IBD (inflammatory bowel disease) is characterized by chronic intestinal inflammation leading to persistent symptoms and a lack of effective treatments. ZP (Zanthoxyli Pericarpium) has been used in traditional Chinese medicine for its anti-inflammatory and antioxidant properties for the management of intestinal disorders. (2) Methods: This study aimed to investigate the components of ZP, their specific targets, and associated diseases using the TCMSP (Traditional Chinese Medicine Systems Pharmacology) analysis platform, TCMBank database, and ETCM2.0 (Encyclopedia of Traditional Chinese Medicine 2.0) database. Additionally, we explored the protective effects of ZP on the colon and the underlying molecular mechanisms in the treatment of IBD. (3) Results: We identified 59 compounds in ZP that target 38 genes related to IBD, including PTGS2, PPARG, and GPBAR1. In a mice model of DSS (dextran sodium sulfate)-induced colitis, ZP significantly reduced colonic epithelial damage and oxidative stress markers, such as iNOS and nitrotyrosine, demonstrating its antioxidant properties. (4) Conclusions: These findings suggest that ZP has protective effects against DSS-induced colonic damage owing to its anti-inflammatory and antioxidant properties, making it a potential candidate for IBD treatment. However, further research and clinical trials are required to confirm its therapeutic potential and safety in humans.

Exploring the prescription laws of bone flaccidity in ancient chinese medical texts based on association rules and latent structure model

Objective: To analyze the identification and typing of bone flaccidity and the law of medication in ancient books based on the Encyclopaedia of TCM (Traditional Chinese medicine) using the hidden structure model. Methods: The formulations for bone flaccidity were searched in the Chinese Medical Code (software), based on which an Excel sheet was created to conduct frequency analysis and construct a matrix of high-frequency medications. The high-frequency medications for bone flaccidity were then analyzed using the Latent 5.0 software and a latent structure model. With SPSS Modeler and Latent 5.0 as the main analysis methods, Chinese medications with a frequency >1.00% were investigated using the latent structure model and association rules, and the medication rules in treating bone flaccidity with TCM were dissected based on the data of frequency. Results: A total of 223 TCM prescriptions were included, with 270 extracted TCM and a total medication frequency of 2340 times. Among them, Achyranthis Bidentatae Radix, Poria, Angelicae Sinensis Radix, Eucommiae Cortex, Rehmanniae Radix Praeparata, and Ginseng Radix Et Rhizoma. They were the high-frequency medicines for treating bone flaccidity, and the efficacy of tonifying medicinal, heat-clearing medicinal, and blood activating and stasis-resolving medicinal were the high-frequency medicinal categories. Through the analysis of the evidence by formula, it was concluded that spleen-kidney yang deficiency, kidney deficiency and blood stasis, kidney yang deficiency, qi deficiency/qi stagnation and blood stasis, and liver and kidney yin deficiency were the 6 main types of bone flaccidity, which was generally in line with the etiology of bone flaccidity, which was caused by kidney yang deficiency and accompanied by malfunction of the liver and kidneys. In ancient books, the regulation of the kidney is put into an important position. In this study, 19 correlative principles for the treatment of bone flaccidity were derived, whose main combinations are Paeoniae Radix Alba - Angelicae Sinensis Radix, Eucommiae Cortex + Poria-Ginseng Radix Et Rhizoma, Dioscoreae Spongiosae Rhizoma + Cuscutae Semen-Eucommiae Cortex. Conclusion: The medication law of bone flaccidity in the Encyclopaedia of TCM mainly shows that it attaches importance to the regulation of tonifying the liver and kidney to strengthen the tendons and bones and emphasizes that the regulation of the three Zang–fu organs, namely the kidney, the liver and the spleen, can play an important role in the treatment of bone flaccidity.

Exploring the anti‑oxidative mechanisms of Rhodiola rosea in ameliorating myocardial fibrosis through network pharmacology and in vitro experiments.

Myocardial fibrosis (MF) significantly compromises cardiovascular health by affecting cardiac function through excessive collagen deposition. This impairs myocardial contraction and relaxation and leads to severe complications and increased mortality. The present study employed network pharmacology and in vitro assays to investigate the bioactive compounds of Rhodiola rosea and their targets. Using databases such as HERB, the Encyclopedia of Traditional Chinese Medicine, Pubchem, OMIM and GeneCards, the present study identified effective components and MF‑related targets. Network analysis was conducted with Cytoscape to develop a Drug‑Ingredient‑Target‑Disease network and the STRING database was utilized to construct a protein‑protein interaction network. Key nodes were analyzed for pathway enrichment using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular interactions were further explored through molecular docking techniques. The bioactivity of salidroside (SAL), the principal component of Rhodiola rosea, against MF was experimentally validated in H9c2 cardiomyocytes treated with angiotensin II and assessed for cell viability, protein expression and oxidative stress markers. Network pharmacology identified 25 active ingredients and 372 targets in Rhodiola rosea, linking SAL with pathways such as MAPK, EGFR, advanced glycosylation end products‑advanced glycosylation end products receptor and Forkhead box O. SAL showed significant interactions with core targets such as albumin, IL6, AKT serine/threonine kinase 1, MMP9 and caspase‑3. In vitro, SAL mitigated AngII‑induced increases in collagen I and alpha smooth muscle actin protein levels and oxidative stress markers, demonstrating dose‑dependent effectiveness in reversing MF. SAL from Rhodiola rosea exhibited potent anti‑oxidative properties that mitigated MF by modulating multiple molecular targets and signaling pathways. The present study underscored the therapeutic potential of SAL in treating oxidative stress‑related cardiovascular diseases.

Exploring the therapeutic efficacy and pharmacological mechanism of Guizhi Fuling Pill on ischemic stroke: a meta-analysis and network pharmacology analysis.

The role of Guizhi Fuling Pill (GZFL) in the treatment of ischemic stroke (IS) is still controversial, and its pharmacological mechanism remains unclear. To evaluate the efficacy and potential pharmacological mechanisms of GZFL on IS, a comprehensive method integrating meta-analysis, network pharmacology, and molecular docking was employed. Eight electronic databases were searched from inception to November 2023. Review Manager 5.4.1 software was used for meta-analysis. Active compounds and targets of GZFL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. Relevant targets of IS were obtained from the DisGeNet, Genecards, and DrugBank databases. GO biological function analysis and KEGG enrichment analysis were performed in the Metascape database. AutoDock Tools and PyMOL software were employed for Molecular docking. The intervention group significantly increased the total effective rate and decreased the NIHSS score. Administration of GZFL also improved the whole blood viscosity (low and high shear rates) and levels of fibrinogen, TNF-α, and IL-6. The key active compounds included quercetin, kaempferol, catechin, and beta-sitosterol, and the core target proteins included SRC, MAPK1, TP53, JUN, RELA, AKT1, and TNF. GO analysis mainly involved inflammation response, cellular response to lipids, and regulation of ion transport. The core pathways were lipid and atherosclerosis, cAMP, calcium, IL-17, and MAPK signaling pathways. Key active compounds showed good affinity with the core targets. The underlying mechanisms of GZFL in IS treatment are primarily related to its anti-inflammatory, anti-atherosclerosis, and neuroprotective effects.

Resveratrol activates MAPK/ERK pathway to regulate oestrogen metabolism in type I endometrial cancer

ObjectiveEndometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated.MethodsThe target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug–disease–target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS.ResultsA total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P < 0.05). The concentrations of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in the endometrial tissue of mice were significantly increased after Res treatment, and those of 4-OHE2 in the serum and uterus of mice were significantly decreased (P < 0.05). Meanwhile, in the MAPK/ERKi intervention group, the effect of Res on the reversal of oestrogen homeostasis imbalance was obviously weakened.ConclusionRes has multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that Res regulates oestrogen metabolism by activating the MAPK/ERK pathway. This finding provides a new perspective for subsequent research on the treatment of endometrial cancer.

Mechanism of Si Ni San Combined with Astragalus in Treating Hepatic Fibrosis: A Network Pharmacology and Molecular Docking Study.

Si Ni San combined with Astragalus (SNSQ) has demonstrated significant efficacy in the treatment of hepatic fibrosis (HF), as confirmed by clinical practice. However, its pharmacological mechanism remains unclear. This study employs network pharmacology to identify key targets and proteins for molecular docking. Additionally, animal experiments were conducted to validate the network pharmacology results, providing further insights into the mechanism of SNSQ in treating HF. Effective compounds of SNSQ were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Molecular formula structures of these effective compounds were obtained from the PubChem database. Partial target proteins with a probability greater than 0.6 were sourced from the SWISS database. Uniprot IDs corresponding to these target proteins were retrieved from the SUPERPRED database. The remaining target proteins of the compounds were obtained from the Uniprot database based on the Uniprot IDs. The drug target proteins were then summarized. Target points related to HF were selected from the GeneCards and OMIM databases. Common target points were identified in the Venn diagram and imported into Cytoscape 3.9.1 software to construct the "SNSQ-effective compound-target pathway-HF" network. AutoDock software was used for molecular docking of compounds and target proteins with high-degree values. The common target points underwent GO function enrichment and KEGG pathway enrichment analysis using the DAVID database. An HF rat model was established, and serum AST and ALT activities were measured. The Hyp assay kit was utilized to detect the Hyp content in liver tissue. To the transcription levels of pro-inflammatory factors (IL-1β, TNF-α, IL-6) and anti-inflammatory factors (IL-10, TGF-β1, IL-4) in rat serum and liver.IL-1β, TNF-α, IL-10, and TGF-β1 were chosen for validation through ELISA. Western blotting and qRT-PCR were used to assess the expression of related proteins, namely NFKB1, NF-κBp65, NF-κBp50, α-SMA, and Col-1 in liver tissue. qRT-PCR was also employed to study the expression of ECM synthesis and proliferation-related genes, including Cyclin D1, TIMP1, COL1A1 in HSC-T6 cells and rat liver tissue, as well as the inhibition of the ECM-related gene MMP13 in HSC-T6 cells and rat liver tissue. A total of 16 valid compounds were predicted, with kaempferol, sitosterol, and isorhamnetin exhibiting high-degree values. KEGG enrichment analysis revealed that the target genes of SNSQ were enriched in multiple pathological pathways, with the NF-Kappa B signaling pathway being predominant. Molecular docking simulations indicated strong affinities between SNSQ's primary components-kaempferol, sitosterol, isorhamnetin-and NFKB1. Experimental results demonstrated significant reductions in AST, ALT, and Hyp levels in the SNSQ group. Pro-inflammatory factors (IL-1β, TNF-ɑ) were markedly reduced, while anti-inflammatory factors (IL-10, TGF-β1) were substantially increased. The protein expression and transcription levels of α-SMA and Col-1 were significantly decreased, whereas those of NFKB1, NF-κBp65, and NF-κBp50 were notably elevated. mRNA expression levels of Cyclin D1, TIMP1, COL1A1 in HSC-T6 cells and rat liver tissue were significantly decreased, whereas MMP13 mRNA expression level was significantly increased. Treatment of HF with SNSQ involves multiple targets and pathways, with a close association with the overexpression of NFKB1 and activation of the NF-Kappa B signaling pathway. Its mechanism is closely linked to the activation of inflammatory responses, HSC activation, and proliferation.

Elucidating the mechanism of action of Isobavachalcone induced autophagy and apoptosis in non-small cell lung cancer by network pharmacology and experimental validation methods

BackgroundLung cancer is the leading cause of cancer deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer-related mortality. In recent years, there have been numerous treatments for non-small cell lung cancer, but the cure and survival rates are still extremely low. Isobavachalcone (IBC) belongs to the chalcone component of the traditional Chinese medicine Psoralea corylifolia L., and is a unique Protein kinase B (AKT) pathway inhibitor with significant anticancer effects. Previous studies have shown that IBC possess a variety of biological properties, including anti-cancer, anti-inflammatory, and antioxidant properties. This study focused on the use of network pharmacology analysis, molecular docking technology and experimental validation to elucidate the potential mechanisms of IBC for the treatment of NSCLC. MethodsScreening key genes and pathways of IBC action in NSCLC using network pharmacology. The IBC target genes were from The Encyclopedia of Traditional Chinese Medicine (ETCM) and BATMAN-TCM databases, the NSCLC target genes were from GeneCards, Online Mendelian Inheritance in Man (OMIM) and The Therapeutic Target database (TTD) databases, both of which were taken as intersecting genes for protein–protein interaction network analysis and enrichment analysis, and the binding energies of the compounds to the core targets were further verified by molecular docking. Cell lines in vitro experiments were then performed to further unravel the mechanism of IBC for NSCLC. ResultsA total of 279 potential targets were retrieved by searching the intersection of IBC and NSCLC targets. Protein-protein interaction (PPI) network analysis indicated that 6 targets, including AKT1, RXRA, NCOA1, RXRB, RARA, PPARG were hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that IBC treatment of NSCLC mainly involves steroid binding, transcription factor activity, Pathways in cancer, cAMP signaling pathway, Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Among them, the AMPK signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of NSCLC. Then, the results of in vitro experiment indicated that IBC could inhibit proliferation of NSCLC cells and induce cell autophagy and apoptosis. The results also showed that IBC could increase the protein expression of AMPK and decrease the protein expression of AKT and mammalian target of rapamycin (mTOR), suggesting that IBC can treat NSCLC by inducing cellular autophagy and apoptosis as well as modulating AMPK and AKT signaling pathways. ConclusionsIn summary, this study provided a new insight into the protective mechanism of IBC against NSCLC through network pharmacology and experimental validation.

Evaluation of the mechanism of Gong Ying San activity on dairy cows mastitis by network pharmacology and metabolomics analysis.

The goal of this investigation was to identify the main compounds and the pharmacological mechanism of the traditional Chinese medicine formulation, Gong Ying San (GYS), by infrared spectral absorption characteristics, metabolomics, network pharmacology, and molecular-docking analysis for mastitis. The antibacterial and antioxidant activities were determined in vitro. The chemical constituents of GYS were detected by ultra-high-performance liquid chromatography Q-extractive mass spectrometry (UHPLC-QE-MS). Related compounds were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, http://tcmspw.com/tcmsp.php) and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/) databases; genes associated with mastitis were identified in DisGENT. A protein-protein interaction (PPI) network was generated using STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment screening was conducted using the R module. Molecular-docking analyses were performed with the AutoDockTools V1.5.6. Fifty-four possible compounds in GYS with forty likely targets were found. The compound-target-network analysis showed that five of the ingredients, quercetin, luteolin, kaempferol, beta-sitosterol, and stigmasterol, had degree values >41.6, and the genes TNF, IL-6, IL-1β, ICAM1, CXCL8, CRP, IFNG, TP53, IL-2, and TGFB1 were core targets in the network. Enrichment analysis revealed that pathways associated with cancer, lipids, atherosclerosis, and PI3K-Akt signaling pathways may be critical in the pharmacology network. Molecular-docking data supported the hypothesis that quercetin and luteolin interacted well with TNF-α and IL-6. An integrative investigation based on a bioinformatics-network topology provided new insights into the synergistic, multicomponent mechanisms of GYS's anti-inflammatory, antibacterial, and antioxidant activities. It revealed novel possibilities for developing new combination medications for reducing mastitis and its complications.

Bioinformatics database and production layout visual analysis platform of medicinal plants:a case study of Dao-di medicinal materials in Sichuan province

In the new stage of trans-omics and trans-subjects for medicinal plants, it is an urgent need to integrate big data, provide interactive applications, and form a unified and multi-level research system and big data platform. Dao-di medicinal material, as an important source of medicinal plants, is a unique quality concept and comprehensive standard of tranditional Chinese medicine(TCM). Several databases have been developed in China and abroad, such as the Encyclopedia of Traditional Chinese Medicine(ETCM) and the Global Pharmacopoeia Genome Database(GPGD). Yet, most databases do not provide multi-dimensional data, including geographic data, phenotype data, compound data, and genetic data. Sichuan, known as the hometown of TCM therapies and the treasure trove of TCM, is the most representative region of medicinal plant diversity in China. According to the latest data of the fourth national survey of TCM resources, there are more than 8 000 TCM and 86 Dao-di medicinal materials in Sichuan province. Based on resource census data and relevant achievements, this study constructed the bioinformatics database of medicinal plants and the visual analysis platform of production layout by taking the Dao-di medicinal materials in Sichuan province as an example, covering geographic data, phenotype data, compound data, and genetic data. It effectively integrates multi-dimensional data of Dao-di medicinal materials and provides different levels of data interaction applications. The platform is the first large-scale multi-dimensional database and visual platform of Dao-di medicinal materials in Sichuan province, which serves as an essential resource for germplasm resources identification, decomposition of biosynthetic pathways, molecular breeding of varieties and provides medicinal plant resource information and data support for development and utilization of medicinal plants in China and abroad.

Network pharmacology, bioinformatics, and experimental validation to identify the role of Hedyotis diffusa willd against gastric cancer through the activation of the endoplasmic reticulum stress

BackgroundGlobally, gastric cancer (GC) is recognized as the third leading cause of cancer-related deaths and the fifth most prevalent malignant disease. Multiple studies have indicated that Hedyotis diffusa Willd, in pinyin, called Bai Hua She Cao (BHSSC), a traditional Chinese medicine (TCM) is an herbal remedy for cancer treatment. However, the specific mechanisms underlying its anti-tumor properties and mode of action are still unclear. MethodsTo determine the role of BHSSC in GC, candidate target genes were selected from The Encyclopedia of Traditional Chinese Medicine (ETCM) and analyzed using network pharmacology, bioinformatics, and experimental validation. Differentially expressed genes (DEGs) associated with gastric cancer were obtained from RNA sequencing (RNA-seq) data sourced from The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD). The Reactome Pathway was examined using Analysis Tools, while KEGG pathways were analyzed using KOBAS. Gene Ontology (GO) evaluations were performed using WebGestalt and DAVID. The relationships between proteins were investigated using the STRING database. Furthermore, cell viability, colony formation, and cell migration ability were conducted in gastric cancer cells, BGC-823 and MGC-803. ResultsNetwork pharmacology and bioinformatics analyses revealed a significant association between BHSSC and metabolic pathways. In vitro experiments demonstrated that BHSSC effectively suppressed gastric cancer cell proliferation and colony formation, inhibited cell migration, and activated the endoplasmic reticulum (ER) stress. Furthermore, it was found that enhancement of the expression of IRE1α and BIP is the mechanism by which BHSSC activates ER stress. ConclusionsThe findings suggest that BHSSC exerts its effects through modulation of metabolic pathways, leading to the suppression of cell proliferation, inhibition of cell migration, and activation of the endoplasmic reticulum. These results provide valuable insights into the mechanisms underlying the therapeutic effects of BHSSC in GC and support its potential as a novel treatment option.

Research on the Mechanism of Traditional Chinese Medicine Treatment for Diseases caused by Human Coronavirus COVID-19

Background: Human coronaviruses are a large group of viruses that exist widely in nature and multiply through self-replication. Due to its suddenness and variability, it poses a great threat to global human health and is a major problem currently faced by the medical and health fields. background: Human coronaviruses are a large group of viruses that exist widely in nature and multiply through self-replication. Due to its suddenness and variability, it poses a great threat to global human health and is a major problem currently faced by the medical and health fields. Objective: COVID-19 is the seventh known coronavirus that can infect humans. The main purpose of this paper is to analyze the effective components and action targets of the Longyi Zhengqi formula and Lianhua Qingwen formula, study their mechanism of action in the treatment of new coronavirus pneumonia (new coronavirus pneumonia), compare the similarities and differences of their pharmacological effects, and obtain the pharmacodynamic mechanism of the two traditional Chinese medicine compounds. Method: Obtain the effective ingredients and targets of Longyi-Zhengqi Formula and Lianhua- Qingwen Formula from ETCM (Encyclopedia of Traditional Chinese Medicine) and other traditional Chinese medicine databases, use GeneCards database to obtain the relevant targets of COVID-19, and use Cytoscape software to build the component COVID-19 target network of Longyi-Zhengqi Formula and the component COVID-19 target network of Lianhua-Qingwen Formula. STRING was used to construct a protein interaction network and screen key targets. GO (Gene Ontology) was used for enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) was used for pathways to find out the targets and pathways related to the treatment of COVID-19. Results: In the GO enrichment analysis results, there are 106 biological processes, 31 cell localization and 28 molecular functions of the intersection PPI network targets of Longyi-Zhengqi Formula- COVID-19, 224 biological processes, 51 cell localization and 55 molecular functions of the intersection PPI network targets of Lianhua-Qingwen Formula-COVID-19. In the KEGG pathway analysis results, the number of targets of Longyi-Zhengqi Formula on the COVID-19 pathway is 7, and the number of targets of Lianhua-Qingwen Formula on the COVID-19 pathway is 19; In the regulation analysis results, Longyi-Zhengqi Formula achieves the effect of treating COVID-19 by regulating IL-6, and Lianhua-Qingwen Formula achieves the effect of treating pneumonia by regulating TLR4. Conclusion: This paper explores the mechanism of action of Longyi-Zhengqi Formula and Lianhua-Qingwen Formula in treating COVID-19 based on the method of network pharmacology, and provides a theoretical basis for traditional Chinese medicine to treat sudden diseases caused by human coronavirus in terms of drug targets and disease interactions. It has certain practical significance.

Research on the Mechanism of Si Xian Decoction in Treating Acute Leukemia Based on Network Pharmacology and Molecular Docking Technology

Abstract Objective Our objective was to investigate the mechanism of action of the Si Xian Decoction (SXD) in treating acute leukemia (AL) using network pharmacology and molecular docking techniques. Methods The chemical components of the four medicinal herbs of Shengdi (Rehmanniae Radix), Baimaogen (Imperatae Rhizoma), Xiaoji (Cirsii Herba), and Pugongying (Taraxaci Herba) in the SXD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM), and Encyclopedia of Traditional Chinese Medicine (ETCM). A natural active chemical component dataset for the SXD was established. Human Gene Database (Gencards), Database of Gene-Disease Associations (DisGeNET), Database for Drug and Drug Target Information (DrugBank), and Human Disease Database (MalaCards) were searched to obtain AL-related targets and to establish a disease target database. After obtaining the intersection targets of drugs and diseases, a Venn diagram of the common targets was drawn online. A drug-disease protein interaction network was constructed using the String 11.5 platform, and a “drug-disease-target-signal pathway” network was built using Cytoscape 3.8.2 software to obtain relevant target network topology parameters. Results By searching the TCMSP, BATMAN-TCM, and ETCM databases, 30 active components of the SXD and 677 related targets were obtained. From Gencards, DrugBank, MalaCards, and DisGeNET databases, 12,110 potential AL disease targets were obtained. Using the ClusterProfiler package of the R4.2.2 platform, 1,011 entries of gene ontology information were enriched, including 467 biological process entries, 236 molecular function entries, and 308 cellular component entries. Additionally, 220 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were obtained, mainly involving chemical carcinogen receptor activation, lipid and atherosclerosis, fluid shear stress and atherosclerosis, prostate cancer, and the role of the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications. Network topology analysis revealed that the main active components of SXD treating AL include γ-aminobutyric acid, adenosine, quercetin, scopolamine, and taraxasterol. Conclusion The treatment of AL with the SXD is a process of multicomponent, multitarget, and multisignal pathway coordination. Network pharmacology provides a solid research basis for elucidating the mechanism of action of SXD in the treatment of AL.

Therapeutic efficacy and pharmacological mechanism of Yindan Xinnaotong soft capsule on acute ischemic stroke: a meta-analysis and network pharmacology analysis.

Yindan Xinnaotong soft capsule (YDXNT), a traditional Chinese medicine preparation, has shown a promising effect in the treatment of acute ischemic stroke (AIS). The goal of this study was to investigate the therapeutic effects and pharmacological mechanisms of YDXNT on AIS. Randomized controlled trials were searched and screened. Review Manager 5.4 was used for a meta-analysis. Active ingredients and targets of YDXNT were extracted from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. AIS-related targets were retrieved from GeneCards, OMIM, and DrugBank databases. We constructed PPI and ingredient-target networks, performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and conducted molecular docking. The YDXNT group had a higher total effective rate and a higher Barthel Index score. YDXNT reduced the low-density lipoprotein cholesterol and the whole blood viscosity at high and shear rates. Our study identified 313 ingredients and 1196 common targets. The key ingredients were mainly quercetin, neocryptotanshinone II, miltionone I, neotanshinone C, and tanshiquinone B, and the key targets were mainly SRC, MAPK3, AKT1, MAPK1, and JUN. GO analysis showed that the core targets mainly involved in atherosclerosis and neural apoptosis. The core pathways were lipid and atherosclerosis, PI3K-Akt, MAPK, and other pathways. Key ingredients exhibited robust binding interactions with core targets. YDXNT could effectively improve the total effective rate, ability of daily life, blood lipids, and blood viscosity. Antiatherosclerotic and neuroprotective effects are the main pharmacological mechanisms.Registration number: CRD42023400127.

Analysis of Shared Mechanisms and Chinese Herbal Medicines Between Osteoporosis and Type 2 Diabetes

Background Osteoporosis (OP) and type 2 diabetes (T2D) are commonly encountered metabolic disorders in clinical practice, but the comorbidity mechanism has not been clarified. This study explored the underlying mechanisms for utilizing bioinformatics methods. Furthermore, it predicted traditional Chinese medicines (TCMs) with preventive and therapeutic effects. Materials and Methods GSE35958 and GSE43950 were retrieved and downloaded from the GEO database, and differential expression analysis was performed to identify differentially expressed genes (DEGs) with similar expression patterns in OP and T2D. Then, the common DEGs were uploaded to the STRING database to construct a protein interaction network. Enrichment analysis of the screened genes was conducted using R language packages. Relevant TCMs were searched and screened based on gene targets using the Encyclopedia of traditional Chinese medicine (ETCM) database. Molecular docking of active ingredients of the TCMs and related gene targets was performed using AutoDock Vina software. Results By analyzing the gene expression microarrays, GSE35958 and GSE43950, 34 genes with the same expression pattern shared by OP and T2D were identified. Among these genes, 32 were upregulated and two were downregulated. Protein interaction network analysis revealed that tumor necrosis factor, vascular endothelial growth factor A, and CD44 might play key roles in the co-pathogenesis of T2D and OP. TCMs, including Wolfberry (枸杞), Ginseng (人参), and Yam (山药), were screened based on key genes. Molecular docking results demonstrated binding activity between all active ingredients and the related gene targets. Conclusion This study explored the potential molecular co-pathogenesis of OP and T2D through bioinformatic analysis and preliminarily predicted traditional herbal medicines that may have preventive and therapeutic effects.

Exploring the Mechanism of Buyang Huanwu Decoction Alleviating Restenosis by Regulating VSMC Phenotype Switching and Proliferation by Network Pharmacology and Molecular Docking.

Buyang Huanwu Decoction (BHD) is used to regulate blood circulation and clear collaterals and is widely used in coronary heart disease. However, the active compounds and the mechanism of BHD used to treat restenosis are less understood. The study aimed to explore the potential mechanism of Buyang Huanwu decoction BHD for the treatment of restenosis using network pharmacology and molecular docking experiments. The bioactive components of BHD and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Encyclopaedia of Traditional Chinese Medicine (ETCM) databases as well as literature. Restenosisassociated therapeutic genes were identified from the OMIM, Drugbank, GEO, and Dis- GeNET databases. Genes related to the vascular smooth muscle cell (VSMC) phenotype were obtained from the gene ontology (GO) database and literature. The core target genes for the drug-disease-VSMC phenotype were identified using the Venn tool and Cytoscape software. Moreover, the "drug-component-target-pathway" network was constructed and analyzed, and pathway enrichment analysis was performed. The connection between the main active components and core targets was analyzed using the AutoDock tool, and PyMOL was used to visualize the results. The "compound-target-disease" network included 80 active ingredients and 599 overlapping targets. Among the bioactive components, quercetin, ligustrazine, ligustilide, hydroxysafflor yellow A, and dihydrocapsaicin had high degree values, and the core targets included TP53, MYC, APP, UBC, JUN, EP300, TGFB1, UBB, SP1, MAPK1, SMAD2, CTNNB1, FOXO3, PIN1, EGR1, TCF4, FOS, SMAD3, and CREBBP. A total of 365 items were obtained from the GO functional enrichment analysis (p < 0.05), whereas the enrichment analysis of the KEGG pathway identified 30 signaling pathways (p < 0.05), which involved the TGF-β signaling pathway, Wnt signaling pathway, TRAF6-mediated induction of NF-κB and MAPK pathway, TLR7/8 cascade, and others. The molecular docking results revealed quercetin, luteolin, and ligustilide to have good affinity with the core targets MYC and TP53. The active ingredients in BHD might act on TP53, MYC, APP, UBC, JUN, and other targets through its active components (such as quercetin, ligustrazine, ligustilide, hydroxysafflor yellow A, and dihydrocapsaicin). This action of BHD may be transmitted via the involvement of multiple signaling pathways, including the TGF-β signaling pathway, Wnt signaling pathway, TRAF6-mediated induction of NF-κB and MAPK pathway, and TLR7/8 cascade, to treat restenosis by inhibiting the phenotype switching and proliferation of VSMC.

Effect of Juanbi Qianggu Formula on biological behaviors of fibroblast-like synoviocytes in rheumatoid arthritis by regulating FGFR1 signaling pathway based on network pharmacology and cell function experiments

This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized &quot;active component-target-signaling pathway&quot; network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.

Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level.

Introduction: Previous studies indicated that Wuda Granule (WDG) has been applied in the treatment of gastrointestinal motility disorder (GMD), but the effect and underlying mechanisms is yet to be elucidated. This study aimed to explore the mechanism and pharmacological effect of WDG for GMD via network analysis, verification of animal experiments and clinical experiments. Methods: The chemical components of WDG were identified from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/index.php), and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/Index/) according to oral bioavailability (OB) ≥ 20% and drug-likeness (DL) ≥ 0.10. The targets of WDG compounds were retrieved from the Swiss Target Prediction database (http://www.swisstargetprediction.ch/) and targets related to GMD were retrieved from GeneCards database (https://www.genecards.org/). Network analysis were performed to screen the key active compounds of WDG and its hub targets. Then the pharmacological effect of WDG were verified via vivo experiments in rats and clinical experiments. Results: The results showed that 117 effective active compounds of WDG were screened and 494 targets of WDG compounds targeting GMD were selected. These targets were involved in the biological process of inflammatory regulation and the regulation of gastrointestinal motility. The mechanism was mainly involved in the regulation of PI3K-Akt signaling pathway and Rap1 signaling pathway. In addition, molecular docking analysis suggested that eight key active compounds of WDG may be mainly responsible for the effect of WDG on GMD by targeting HARS, AKT, and PIK3CA, respectively. Animal experiments and clinical trials both suggested that WDG could exert therapeutical effect on GMD via inhibiting inflammation and promoting gastrointestinal motility, it could also improve digestive function of patients with laparoscopic colorectal cancer after surgery. Conclusion: This study was the first to demonstrate that WDG improved GMD mainly via inhibiting inflammatory level and promoting gastrointestinal motility, providing new insights for the understanding of WDG for GMD, inspiration for future research and reference for clinical strategy in terms of the treatment of GMD.

Similarity and Specificity of Lianhua Qingwen and Damp-Heat Plague Formula for the Management of Mild COVID-19

Lianhua Qingwen (LHQW) and damp-heat plague formula (DHPF) have positive therapeutic outcomes on coronavirus disease 2019 (COVID-19). This study aimed to clarify the mechanisms of LHQW and DHPF in COVID-19 treatment, and examined the differences between the 2 formulas in the treatment process. This study is based on systems biology and network pharmacology; the Traditional Chinese Medicine Systems Pharmacology database and Encyclopedia of Traditional Chinese Medicine were used to compare information on LHQW and DHPF; the STRING database was used to construct the “protein–protein interaction (PPI)” and protein module networks. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were used to analyze the intersecting targets of LHQW and DHPF. Ingenuity Pathway Analysis was used to analyze the specific targets of the 2 formulas. Molecular docking and molecular dynamic simulation were used to validate the interactions of candidate active compounds and targets. The results show that both LHQW and DHPF alleviate mild COVID-19 by relieving inflammation, increasing immunity, apoptosis, and reducing oxidative stress. Furthermore, Machiline and Estrone in Armeniacae Semen Amarum (Kuxingren) in LHQW can target neurological disease-related genes (ADRA2B, ADRA2C, and DRD2). In contrast, Ellagic acid in Paeoniae Radix Rubra (Chi Shao) in DHPF can target immunity- and inflammation-related genes (GSTA1 and GSTA2). These findings suggest that when translated into clinical applications, LHQW would likely be more potent in treating patients with nervous disorders who experienced mild COVID-19, whereas DHPF would effectively perform antioxidant and anti-inflammatory activities.

Molecular Mechanisms of Notopterygii rhizoma Et Radix for Treating Arrhythmia Based on Network Pharmacology.

To explore the possible mechanism for treating NRR in arrhythmia using network pharmacology and molecular docking in this study. Active compounds and targets for NRR were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform, SymMap, and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Arrhythmia-related genes were acquired from the Comparative Toxicogenomics Database (CTD) and the GeneCards database. Overlapping targets of NRR associated with arrhythmia were acquired and displayed via a Venn diagram. DAVID was applied for GO and KEGG pathway analyses. Cytoscape software and its plug-in were used for PPI network construction, module division and hub nodes screening. Auto- Dock Vina and qRT-PCR were carried out for validation. In total, 21 active compounds and 57 targets were obtained. Of these, coumarin was the predominant category which contained 15 components and 31 targets. There were 5 key targets for NRR in treating arrhythmia. These targets are involved in the apoptotic process, extrinsic apoptotic signaling pathway in the absence of ligand, and endopeptidase activity involved in the apoptotic process by cytochrome c. The main pathways were the p53 signaling pathway, Hepatitis B and apoptosis. The molecular docking and qRT-PCR displayed good effects on hub node regulation in NRR treatment. NRR plays an important role in anti-apoptotic mechanisms that modulate the p53 signaling pathway, which may provide insight for future research and clinical applications focusing on arrhythmia therapy.

Network Pharmacology Prediction to Explore the Potential Mechanism of Qing'E Pills

Qing’E pills are a classical formula in traditional Chinese medicine that has the effect of tonifying the kidneys and strengthening the bones, first appearing in the tonic formulae in prescriptions of peaceful benevolent dispensary (10th century CE). To preliminarily elucidate the potential mechanisms of Qing’E pills in the treatment of postmenopausal osteoporosis based on network pharmacology. The principal components and corresponding protein targets of Qing’E pills were searched on traditional Chinese medicine systems pharmacology, bioinformatics analysis tool for molecular mechanism-traditional Chinese medicine, SymMap and encyclopedia of traditional Chinese medicine and the compound-target network was constructed by Cytoscape 3.9.1. The targets of postmenopausal osteoporosis were searched on online mendelian inheritance in man, GeneCards, histidine triad nucleotide binding protein and DisGeNET databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into the search tool for retrieval of interacting genes database to construct a protein-protein interaction network. We further performed gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses on the targets. The 33 active compounds in Qing’E pills corresponded to 433 targets. 1647 targets were associated with postmenopausal osteoporosis disease. The active compounds with high degree values were quercetin, stearic acid and marine. The proteins with higher values in the protein-protein interaction network were mitogenactivated protein kinase 1, protein kinase B, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphoinositide-3-kinase regulatory 1, amyloid beta precursor protein, Src proto-oncogene, nonreceptor tyrosine kinase, mitogen-activated protein kinase 8, heat shock protein 90 alpha family class A member 1, epidermal growth factor receptor, and Janus kinase 2. Gene ontology and Kyoto encyclopedia of genes and genomes analysis showed that Qing’E pills treatment of postmenopausal osteoporosis involves signaling pathways that mainly include the tumor necrosis factor signaling pathway, osteoclast differentiation, Wnt signaling pathway and estrogen signaling pathway. We revealed the active ingredients and potential molecular mechanism of Qing’E pills in the treatment of postmenopausal osteoporosis and provided a reference for subsequent basic research