Traditional Chinese Medicine Systems Research Articles

Predicting and Validating the Mechanism of Action of the Enema Formula in Treating Colorectal Cancer by Using Network Pharmacology, GEO, and TCGA Databases

Background: The GCF, created by Professor Liu Shenlin, an esteemed expert in traditional Chinese medicine, is rooted in principles to improve blood flow, relieve blood congestion, clear heat, and detoxify the body. Developed as an empirical formula, it holds significance in CRC treatment. Objective: This study aimed to predict and confirm the active elements, possible targets, and molecular mechanisms against colorectal cancer (CRC) in the GCF enema formula. Methods: Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we screened active elements and drug targets. Colorectal cancer (CRC)-related targets were collected from the Online Mendelian Inheritance in Man (OMIM) database, Disease Gene Network (DisGeNET) database, and Therapeutic Target Database (TTD). The overlap between action targets of all active elements and CRC-related targets was determined to find common targets. A Protein-Protein Interaction (PPI) network of common targets was built using the String database, and Cytoscape software was used for visual analysis to identify core targets. Simultaneously, the common targets were analyzed using the Metascape database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Additionally, core targets and active elements were tested using Discovery Studio 2019 for molecular docking. Furthermore, the expression differences and prognostic impacts of core targets were examined across various cancer databases. Results: Screening revealed 90 active elements and 251 drug targets in the GCF. There were 6113 disease targets, with 113 common targets between CRC and the GCF. Core targets identified through PPI analysis included AKT1, STAT3, MYC, SRC, EGFR, and IL6. KEGG enrichment analysis uncovered 101 relevant pathways related to these targets. Molecular docking experiments confirmed favorable interactions between core targets and multiple active elements in the GCF. Additionally, examination of the Human Protein Atlas (HPA) database highlighted differential expression of core targets MYC and EGFR in normal colorectal tissue compared to CRC tissue. Conclusion: The GCF, comprising a combination of three drugs, appears to counteract CRC by influencing core targets, such as AKT1, STAT3, MYC, SRC, EGFR, and IL6. This process involves regulating multiple cancer-related signaling pathways, notably the PI3K-AKT pathway.

Exploration of the potential mechanism of Yiyi Tongfeng Formula in the treatment of acute gouty arthritis based on network pharmacology and molecular docking: A review.

The global prevalence of gout is on the rise. Yiyi Tongfeng Formula (YTF), a traditional herbal compound, has gained recognition for its efficacy in managing acute gouty arthritis (AGA). Despite its widespread use, the underlying mechanisms of YTF in AGA treatment remain largely undefined. This study employed network pharmacology and molecular docking to elucidate these mechanisms. We utilized the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, SymMap database, and various literature sources to identify active components and corresponding targets of YTF. Relevant AGA-associated targets were identified through the Genecards, Drugbank, Therapeutic Target Database, and Online Mendelian Inheritance in Man databases. A protein-protein interaction network was constructed to delineate interactions between YTF targets and AGA. Key ingredients and central targets were further analyzed using Cytoscape. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were conducted via Metascape. Additionally, molecular docking studies were performed using PyMOL and AutoDock4. It was found that quercetin, kaempferol, and luteolin may be the main active components of YTF for AGA treatment. Gene Ontology enrichment analysis shows that the main biological processes involved are cellular responses to lipids, and inflammatory responses. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggests the involvement of the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and so on. The findings suggest a multi-faceted therapeutic approach of YTF in treating AGA, involving multiple components, targets, biological processes, and signaling pathways. This comprehensive mechanism offers a foundation for further experimental validation.

Network pharmacology integrated with molecular docking and molecular dynamics simulations to explore the mechanism of Tongxie Yaofang in the treatment of ulcerative colitis.

Tongxie Yaofang (TXYF), a classical traditional Chinese medicine, is commonly used in China to treat ulcerative colitis (UC). The aim of this study was to integrate network pharmacology with molecular docking and molecular dynamics simulations to explore the mechanism of Tongxie Yaofang in the treatment of UC. The traditional Chinese medicine systems pharmacology database was used to retrieve the relevant chemical compositions of the herbs contained in TXYF. The DisGeNET, GeneCards, Online Mendelian Inheritance in Man, and Therapeutic Target Database databases were used to retrieve UC-related targets. To construct protein-protein interaction networks and screen for key targets, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses of the key targets of TXYF in the treatment of UC were performed using R 4.3.2 software. AutoDock Tools 1.5.7 was used for molecular docking. Molecular dynamics simulations of protein complexes and complexes of proteins with small-molecule ligands and eutectic ligands were carried out with Gromacs 2022 software. Network pharmacology analysis revealed that TXYF could act on UC through multiple targets and pathways. It may exert therapeutic effects mainly through the AGE/RAGE, TOLL, JAK/STAT, and Th17 signaling pathways. The possible targets of TXYF in the treatment of UC could be AKT1, BCL2, EGFR, HMOX1, HSP90AA1, and TGFβ1. Molecular docking analysis revealed that AKT1 had the highest binding energy (-10.55 kcal/mol). Molecular dynamics simulations revealed that the complexes formed by the AKT1 protein and the chemical compounds MOL001910 and MOL00035 had good stability and high binding strength. AKT1 may be the most critical target of TXYF in treating UC, and the key chemical components of TXYF in treating UC may include β-sitosterol (MOL000358) and 11alpha,12alpha-epoxy-3beta-23-dihydroxy-30-norolean-20-en-28,12beta-olide (MOL00 1910). This study revealed that TXYF may exert therapeutic effects on UC through multiple targets, multiple biological functions, and multiple signaling pathways. This study provides a new insight into the pharmacological mechanism of TXYF in treating UC.

New molecular mechanisms of quercetin in improving recurrent spontaneous abortion based on in-depth network pharmacology and molecular docking.

The increasing prevalence of recurrent spontaneous abortion (RSA) poses significant physical and psychological challenges for affected individuals. Quercetin, a natural plant flavonoid, shows promise in reducing miscarriage rates, yet its precise mechanism remains elusive. This study uses network pharmacology, molecular docking, and experimental validation to explore the molecular pathways through which quercetin mitigates RSA. Quercetin-related target genes were sourced from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and RSA target genes were retrieved from the Comparative Toxicogenomics Database (CTD), with overlapping targets identified using Venn diagrams. All genes were visualized using the STRING database, and core targets were selected with Cytoscape 3.7.3. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the DAVID and Reactome online resources. Subsequently, HTR-8/SVneo cells were stimulated with lipopolysaccharide (LPS) and treated with varying concentrations of quercetin (1, 5, and 10μM), then subjected to CCK-8, wound healing, transwell, and annexin V-FITC/PI apoptosis assays. Reverse-transcription quantitative PCR was used to determine the mRNA expression levels of IL-1β, TNF-α, and IL-6 in LPS-induced cells post-quercetin intervention, and western blotting was used to measure AKT1, MMP9, and caspase-3 protein levels. A total of 139 quercetin-associated target genes were identified from the TCMSP database, and 98 disease-associated target genes were obtained from the CTD, resulting in 25 shared target genes. Gene ontology enrichment highlighted the involvement of these targets in positive regulation of apoptosis, response to hypoxia, and intrinsic apoptotic signaling pathway in response to DNA damage. KEGG pathway analysis indicated enrichment in pathways related to interleukin-4 and interleukin-13 signaling, cytokine signaling in the immune system, and apoptosis. Molecular docking studies revealed robust binding of quercetin with MMP9, AKT1, IL-1β, TNF, and caspase-3. In vitro experiments demonstrated that quercetin enhanced LPS-induced cell activity, fostering proliferation, migration, and invasion, and reducing apoptosis. Moreover, quercetin reduced IL-1β, TNF-α, and IL-6 mRNA expression, increased AKT1 and MMP9 protein levels, and reduced caspase-3 expression. Quercetin could mitigate the incidence of RSA by modulating inflammatory responses and apoptotic processes, through upregulation of AKT1 and MMP9, and downregulation of caspase-3, IL-1β, TNF-α, and IL-6. Quercetin opens up a new way of thinking about treating RSA.

Scientific exploration and hypotheses concerning the meridian system in traditional Chinese medicine

The meridian theory is an important component of traditional Chinese medicine, playing a crucial role in disease diagnosis, treatment, and health preservation. Serving as the media for the effects of acupuncture, moxibustion, herbal medicine, and acupressure massage, meridians exert undeniable impact on the human body. However, the essence of meridians remains a topic of debate. Recent research has primarily focused on their anatomical structures, leading to numerous hypotheses. Simultaneously, other researchers have approached this subject from an energetic perspective, discovering information interactions within the meridian system. These findings suggest that meridians possess both physical and information dimensions, indicating that a singular approach to their study is insufficient. To bridge this gap, a shift from purely structural research toward an exploration of the information aspects of meridians is necessary. By integrating this information approach with traditional meridian theory, it may be possible to develop a new, modernized meridian theory that is aligned with contemporary concepts, making it more accessible and applicable in clinical settings.

Exploration of Active Ingredients, Targets, and Potential Mechanisms of Er-Miao-San in the Treatment of Colorectal Cancer Based on Network Pharmacology and Molecular Docking Technology

Background Er-Miao-San (EMS) is a classic prescription in Traditional Chinese Medicine (TCM) for the treatment of colorectal cancer (CRC) and has shown promising therapeutic effects in clinical practice. However, the specific components and molecular mechanisms of EMS remain unclear. Purpose The aim of this study was to analyze the effective components and molecular mechanisms of EMS in treating CRC through network pharmacology techniques and experimental validation. Materials and Methods The Traditional Chinese Medicine Systems Pharmacology database was used to screen the main active chemical components and targets of the EMS formula. The compound structures were verified using the PubChem database, which is an organic small-molecule bioactivity database. GeneCards and OMIM databases were utilized to predict target genes related to CRC. The Cytoscape 3.8 software was used to construct a “Drug-Active Ingredient-Target-Disease” intersection network. The STRING database was employed to analyze the core target protein–protein interaction network shared by EMS and CRC. The core targets were further subjected to Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the R language. Molecular docking between the core targets and the major active chemical components of EMS was performed using AutoDock software. The impact of the core targets on the prognosis of CRC patients was analyzed using the R language. Subsequently, we validated the potential mechanisms predicted by network pharmacology for the inhibition of CRC cell proliferation by the key proteins in the relevant pathways through CCK8 cell proliferation assays and Western blot experiments. Results Molecular docking results showed good docking affinity between the key active components, such as quercetin and baicalein, of EMS and the core targets. Kaplan–Meier survival analysis demonstrated a close correlation between the core targets and the survival prognosis of CRC patients. Cellular experiments showed that EMS significantly inhibited the proliferation of CRC cells and may promote apoptosis and autophagy of CRC cells by suppressing the expression of key proteins in the PI3K/AKT pathway. Conclusion The TCM formula EMS exerts anti-CRC effects through multiple pathways and targets, improving the prognosis and extending the survival period of CRC patients. This study provides preliminary insights into the effective components and molecular mechanisms of EMS in the treatment of CRC, which were preliminarily validated through molecular docking and experimental approaches.

A Network Pharmacological Study on the Treatment of Diminished Ovarian Reserve with Nourishing Yin Formula

Objective To identify the principal constituents of Nourishing Yin Formula, analyze its active substances and effective targets for treating DOR, and explore its potential mechanism of action. Methods The primary active constituents of Nourishing Yin Formula and their putative targets for treating DOR were identified through a search of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (BATMAN-TCM), GeneCards, OMIM, and Uniprot databases. A protein-protein interaction network was constructed using the String database to identify shared targets between the drug and disease. These drug-disease shared targets were then subjected to GO analysis and KEGG pathway enrichment analysis using the DAVID database. Results After screening, the primary chemical constituents of Nourishing Yin Formula for treating DOR were identified, including progesterone, beta-sitosterol, 17-Beta-Estradiol, quercetin, kaempferol, etc Among the 52 critical targets for Nourishing Yin Formula in DOR treatment, the core targets were AKT1, INS, IL6, TNF, EGFR, ESR1, MYC, CTNNB1, NOS3, ERBB2, EDN1, and ESR2. Conclusions The potential mechanism of Nourishing Yin Formula in the treatment of DOR may involve the herbal compound's impact on AKT1, INS, IL6, TNF, and EGFR pathways. It regulates ovarian granulosa cell proliferation and apoptosis, and restores ovarian blood supply.

Effect and Mechanisms of Huangqi-Shanzhuyu in the Treatment of Diabetic Nephropathy based on Network Pharmacology and In Vitro Experiments.

Huangqi-Shanzhuyu (HS), a classic combination of Chinese herbal formulae, has been widely used for the treatment of diabetic nephropathy (DN). However, its pharmacological mechanism of action is still unclear. The active ingredients of HS and their potential targets were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the DN-related targets were determined from GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGkb, and Therapeutic Target Database (TTD). The Cytoscape software was used to construct a herb-disease-target network and screen core genes. STRING was employed to generate a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the mechanism of action of HS in DN. Animal experiments and molecular docking were used to verify the potential mechanism. In total, 40 active ingredients and 180 effective targets of HS in DN were identified and 1115 DN-related targets were retrieved. From the PPI network, VEGFA, AKT1, IL6, IL1B, TP53, MMP9, PTGS2, CASP3, EGF and EGFR were identified as core genes. The anti-DN mechanism mainly involved multiple signaling pathways such as AGEs-RAGE. Animal experiments and molecular docking analysis confirmed that HS downregulated the expression of IL-1 and IL-6 via kaempferol-mediated inhibition of JNK1 phosphorylation. HS exhibits a therapeutic effect in DN through its multiple ingredients that act on several targets and multiple signaling pathways, including AGEs-RAGE.

Network pharmacology, molecular docking, and molecular dynamics simulations shed light on the mechanism behind Gynostemma pentaphyllum's efficacy against osteosarcoma.

Osteosarcoma (OS) is the most common type of malignant bone tumor, that poses a serious threat to the lives and health of children and adolescents. Traditional Chinese medicines (TCM) have gained attention for treating OS because of their potent anti-cancer effects and fewer side effects. It is commonly understood that Gynostemma pentaphyllum (Thunb.) Makino (GP) exhibits inhibitory effects on most tumors. However, the knowledge of the systematic mechanisms involved is limited. In this study, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was searched to screen the effective ingredients and corresponding target genes of GP, and disease target databases were searched to identify relevant targets for OS. Venn analysis was used to visualize overlapping genes, which were further extracted using the protein-protein interaction network. R software was used to conduct gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis, molecular docking and molecular dynamics simulation further validate the binding efficacy of potential therapeutic targets to compound molecules. In total, 161 and 1981 proteins were identified as target genes of GP and OS, respectively, and 104 overlapping genes were identified. Through analysis of the core subnetwork, 12 hub genes were identified, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the PI3K/Akt signaling pathway was the most significant. Molecular docking and molecular dynamics simulations show that a high affinity between quercetin and these targets, especially with the combination of TNF free energy (Δ Gbind) minimum, MM/PBSA and MM/GBSA is 42.85 kcal/mol, respectively, and 45.29 kcal/mol. The active ingredients Rhamnazin and Quercetin in Gypenoylum play a therapeutic role in OS through several key targets and pathways. This study provides ideas and references for further research on drug development.

Efficacy of Qi-Gen powder for immunity enhancement and investigation of its therapeutic mechanisms through gene expression profiling

Infection with different viruses threatens the health of animals in the livestock and poultry industry. Immunopotentiators can increase natural immunity and vaccination efficacy; however, most are expensive chemical and biological compounds with questionable safety. Traditional Chinese medicines (TCMs) such as Yupingfeng (YPF), a well-known immunomodulatory remedy, provide healthy alternatives to such agents. The aim of this study was to examine the therapeutic properties of Qi-Gen powder (QG) and compare them with those of YPF. The immune organ index, cytokine levels, and other indicators were utilized to evaluate the effects of QG in an immunosuppression mouse model. QG was further assessed for its ability to enhance vaccine effectiveness in chickens immunized for Newcastle disease virus (NDV). Potential therapeutic mechanisms and targets of QG were examined in the breast cancer cell line MCF-7 using microarray technology combined with the TCM systems pharmacology database of known targets. Compared with model controls, QG improved immunological function, outperforming YPF in mice. QG also enhanced the immunological response to NDV vaccine in immune organs and increased feed intake of chickens. Further research is needed to validate the link between the PI3K/Akt/GSK-3 pathway and the immune-boosting effects of QG.

Studies on the Anti-Inflammatory Effect of Xiaoyao Pills in The Treatment of Postmenopausal Osteoporosis in Mice.

Osteoporosis is a common metabolic disease of elderly and postmenopausal women, with no obvious symptoms during its early stages. In the latter stages of this condition, the patients are prone to fractures, and this can seriously affect their health and quality of life. The worldwide increase in life expectancy has made osteoporosis a global concern. The Xiaoyao pills were previously used in the treatment of depression. In addition, the drug appeared to have estrogen-like activity, which affected the expression of ALP, an early osteoblast-specific marker, and COL-1, a major component of bone extracellular matrix. Xiaoyao pills were assessed for their effects on postmenopausal osteoporosis (PMOM) in mice. The target information of each herbal component of Xiaoyao pills was accessed through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Information from GeneCards, OMIM, PharmGkb, TTD, DrugBank, and other websites was used to construct the regulatory network of the herbal complex through Cytoscape and String network to assess the protein interactions. Mice were ovariectomized, and treated with high and low doses of Xiaoyao pills and these were compared to controls. Their symptoms were assessed by immunocytochemistry of bone tissues. The results suggested that Xiaoyao pills had the ability to alleviate the symptoms of PMOM in ovariectomized mice through the IL-17 signaling pathway. This drug has the potential to become a novel therapeutic agent for the treatment of osteoporosis.

Network pharmacology and molecular docking reveal potential mechanisms of ginseng in the treatment of diabetes mellitus-induced erectile dysfunction and asthenospermia.

Diabetes mellitus (DM) is a chronic metabolic disease that predisposes to chronic damage and dysfunction of various organs, including leading to erectile dysfunction (ED) and asthenospermia. Literature suggests that ginseng plays an important role in the treatment and management of DM. Ginseng may have a therapeutic effect on the complications of DM-induced ED and asthenospermia. The study aimed to explore the mechanisms of ginseng in the treatment of DM-induced ED and asthenospermia following the Traditional Chinese Medicine (TCM) theory of "treating different diseases with the same treatment." This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of Ginseng for the treatment of DM-induced ED and asthenospermia. The chemical ingredients and targets of ginseng were acquired using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. The targets of DM, ED, and asthenospermia were extracted with the GeneCards and Online Mendelian Inheritance in Man databases. A protein-protein interaction network analysis was constructed. The Metascape platform was applied for analyzing the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. AutoDock Vina was used to perform molecular docking. Network pharmacology revealed that the main active components of the target of action were kaempferol, beta-sitosterol, ginsenoside rh2, stigmasterol, and fumarine. Core targets of the protein-protein interaction network included TNF, IL-1β, AKT1, PTGS2, BCL2, and JUN. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that they were mainly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, Lipid and atherosclerosis. The interactions of core active components and targets were analyzed by molecular docking. Ginseng may play a comprehensive therapeutic role in the treatment of DM-induced ED and asthenospermia through "multicomponent, multi-target, and multi-pathway" biological mechanisms such as inflammation and oxidative stress.

Analysis of core functional components in Yinchenhao Decoction and their pathways for treating liver fibrosis

To analyze the core functional component groups (CFCG) in Yinchenhao Decoction (YCHD) and their possible pathways for treating hepatic fibrosis based on network pharmacology. PPI data were extracted from DisGeNET, Genecards, CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1. The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction. A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets. In cultured human hepatic stellate cells (LX-2 cells), the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay; the effects of these compounds on collagen α1 (Col1a1) mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting. A total of 1005 pathogenic genes, 226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained. Benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid were selected for CCK-8 verification, and they all showed minimal cytotoxicity below the concentration of 200 μmol/L. Clorius, polydatin, lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation. At the concentration of 200 μmol/L, all these 4 components inhibited PI3K, p-PI3K, AKT, p-AKT, ERK, p-ERK, P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells. The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate, vanillic acid, clorius, polydatin, lauric acid and ferulic acid, which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

The potential of Gynostemma pentaphyllum in the treatment of hyperlipidemia and its interaction with the LOX1-PI3K-AKT-eNOS pathway.

Gynostemma pentaphyllum, a traditional Chinese medicine, is widely used to treat various diseases, but its therapeutic effects and mechanisms of action on hyperlipidemia remain unclear. This study aims to investigate the effects of Danshen leaf on hyperlipidemia through network pharmacology, molecular docking, and cellular experiments, elucidating its multifaceted mechanism of action within the LOX1-PI3K-AKT-eNOS pathway. First, the active ingredients and targets of G. pentaphyllum were screened using the Traditional Chinese Medicine Systems Pharmacology database. Then, targets for hyperlipidemia were identified using the OMIM and GeneCards databases, and potential therapeutic targets for G. pentaphyllum in treating hyperlipidemia were determined. An active ingredient-target network was constructed using Cytoscape software, and a protein-protein interaction (PPI) network was built and visualized using the STRING database and Cytoscape software. Finally, GO functional and KEGG pathway enrichment analyses were performed, and the predicted mechanisms were validated through molecular docking and cell experiments. 85 targets for G. pentaphyllum and 1556 for Hyperlipidemia were screened, with 53 common targets. Twenty-four active ingredients of G. pentaphyllum were found to be involved in the treatment of hyperlipidemia. Key nodes such as Rhamnazin, Isofucosterol, and quercetin, and targets NCOA2, NR3C2, PGR, and PPARG showed high relevance. In the PPI network, 8 nodes, including IL6, PPARG, and VEGFA, exhibited high centrality. GO functional and KEGG pathway enrichment analyses indicated that G. pentaphyllum may treat hyperlipidemia by influencing various biological functions and pathways, such as DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and lipid and atherosclerosis. Cell experiments demonstrated that G. pentaphyllum significantly regulated the expression of key proteins in the LOX1-PI3K-AKT-eNOS pathway, thereby improving hyperlipidemia. G. pentaphyllum improves hyperlipidemia by mediating the LOX1-PI3K-AKT-eNOS pathway. This study provides a new theoretical basis and experimental evidence for applying G. pentaphyllum to treating hyperlipidemia.

Exploration of novel human neutrophil elastase inhibitors from natural compounds: Virtual screening, in vitro, molecular dynamics simulation and in vivo study

BackgroundHuman neutrophil elastase (HNE) is an important contributor to lung diseases such as acute lung injury (ALI) or acute respiratory distress syndrome. Therefore, this study aimed to identify natural HNE inhibitors with anti-inflammatory activity through machine learning algorithms, in vitro assays, molecular dynamic simulation, and an in vivo ALI assay. MethodsBased on the optimized Discovery Studio two-dimensional molecular descriptors, combined with different molecular fingerprints, six machine learning models were established using the Naïve Bayesian (NB) method to identify HNE inhibitors. Subsequently, the optimal model was utilized to screen 6925 drug-like compounds obtained from the Traditional Chinese Medicine Systems Pharmacy Database and Analysis Platform (TCMSP), followed by ADMET analysis. Finally, 10 compounds with reported anti-inflammatory activity were selected to determine their inhibitory activities against HNE in vitro, and the compounds with the best activity were selected for a 100 ns molecular dynamics simulation and its anti-inflammatory effect was evaluated using Poly (I:C)-induced ALI model. ResultsThe evaluation of the in vitro HNE inhibition efficiency of the 10 selected compounds showed that the flavonoid tricetin had the strongest inhibitory effect on HNE. The molecular dynamics simulation indicated that the binding of tricetin to HNE was relatively stable throughout the simulation. Importantly, in vivo experiments indicated that tricetin treatment substantially improved the Poly (I:C)-induced ALI. ConclusionThe proposed NB model was proved valuable for exploring novel HNE inhibitors, and natural tricetin was screened out as a novel HNE inhibitor, which was confirmed by in vitro and in vivo assays for its inhibitory activities.

The comprehensive evaluation and mechanism of HOUTTUYNIA CORDATA (Thunb) injection as a complementary therapy for infantile pneumonia

BackgroundHouttuynia cordata injection (HCI), a commercialized product made from the active ingredients extracted from Houttuynia cordata Thunb, has been used clinically in China for >50 years with significant therapeutic effects on pseudorabies herpesvirus infection in vitro and H1N1 influenza virus in mice. Purpose of studyThis work is to evaluate the complementary therapeutic effect of HCI on infantile pneumonia (IP) and to explore its mechanism of action. Study designFirst, the complementary efficacy of HCI in improving IP was evaluated by meta-analysis, with only randomized controlled trials from 5 electronic databases were included in this study. Second, network pharmacology was employed to predict the underlying mechanism of HCI in improving IP. Finally, molecular docking, surface plasmon resonance (SPR) and lipopolysaccharide (LPS)-induced rat IP model were used to verify the predicted results. ResultsMeta-analysis indicated that HCI can complementarily improve pneumonia by increasing cure rate and reducing the duration of fever, cough, and wheezing. Network pharmacology analysis using databases such as Traditional Chinese Medicine Systems Pharmacology (TCMSP), Swiss target prediction, Therapeutic target database and Genecards showed that quercetin, houttuynin and kaempferol in HCI are the main compounds that improve IP and regulate 96 pneumonia-related protein targets. Protein-protein interaction (PPI) network analysis indicated that interleukin-6, tumor necrosis factor α (TNF-α), interleukin-1 β (IL-1β), protein kinase B-1, matrix metalloproteinase 9, interleukin-10, tumor protein 53, epidermal growth factor receptor, C-X-C motif chemokine 8 and interferon gamma are the ten most relevant targets of HCI in improving IP. In the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, 96 targets are involved in 706 GO functions and 148 KEGG pathways. Among them, TNF-α/IL-1β signaling associated with inflammatory response is considered to be an important mechanism in IP. Molecular docking, SPR and LPS-induced IP model confirmed the predicted results. ConclusionsHCI has a complementary therapeutic effect on IP, and its mechanism may be related to the inhibition of TNF-α/IL-1β inflammatory response by two flavonoid compounds.

Elucidating the Mechanism of Jisheng Shenqi Pills in the Treatment of Diabetic Kidney Disease: Network Pharmacology Combined with Experimental Verification.

While the annual incidence of diabetic kidney disease (DKD) has been soaring, the exact mechanisms underlying its onset and progression remain partially understood. The present study delved into the underlying mechanisms of Jisheng Shenqi Pill (JSP) in the treatment of DKD. The active constituents and prospective targets of JSP were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), while DKD-associated disease targets were obtained from the GeneCards database. Subsequently, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to assess the overlapping segment of drugs and disease targets. Meanwhile, a component-target-pathway network was constructed to identify pivotal components, targets, and pathways. Molecular docking and molecular dynamics simulation were also carried out to validate the binding efficacy of the pivotal components with the targets. Finally, animal experiments were conducted to corroborate the efficacy of the aforementioned targets and pathways. According to bioinformatics analysis, the primary targets included JUN, TNF, and BAX, while the pivotal pathways involved were AGE/RAGE and PI3K/AKT signaling cascades. In vivo experiments demonstrated that JSP effectively mitigated renal impairment in DKD by reducing renal inflammation and apoptosis. This effect was presumably achieved by modulating the AGERAGE axis and the PI3K/AKT signaling pathway. Our findings imply that JSP could ameliorate renal inflammation and apoptosis in DKD mice by modulating the AGE/RAGE axis and the PI3K/AKT signaling pathway. These findings provide valuable insights into traditional Chinese medicine-based treatments for DKD.

Research and Analysis on the Pathogenesis of Allergic Rhinitis in Children and Its Treatment by Chinese and Western Medicine

Allergic rhinitis in children is a common allergic disease, when it recurs, the symptoms are significant, long-lasting, to children's daily life and learning has brought a huge burden.Western medicine has abundant clinical experience in treating this kind of disease, but the unique dialectical thinking and treatment system of traditional Chinese medicine also show undeniable advantages.The purpose of this study was to explore the etiology of allergic rhinitis in children, the relationship between allergic rhinitis and TCM syndrome types, and the advantages and disadvantages of TCM and WM treatment.It is found that allergen, heredity, environmental factors and immune imbalance are the common causes leading to high incidence of diseases. On the whole, TCM can classify different syndrome types and apply corresponding treatment methods, effective relief of the disease, improve the quality of life.We hope this paper can provide a new perspective and guidance for clinical diagnosis and treatment.

Exploring the pharmacological mechanism of Xianlingubao against diabetic osteoporosis based on network pharmacology and molecular docking: An observational study.

Xianlinggubao formula (XLGB), is a traditional Chinese compound Medicine that has been extensively used in osteoarthritis and aseptic osteonecrosis, but its curative effect on diabetic osteoporosis (DOP) and its pharmacological mechanisms remains not clear. The aim of the present study was to investigate the possible mechanism of drug repurposing of XLGB in DOP therapy. We acquired XLGB active compounds from the traditional Chinese medicine systems pharmacology and traditional Chinese medicines integrated databases and discovered potential targets for these compounds by conducting target fishing using the traditional Chinese medicine systems pharmacology and Swiss Target Prediction databases. Gene Cards and Online Mendelian Inheritance in Man® database were used to identify the DOP targets. Overlapping related targets between XLGB and DOP was selected to build a protein-protein interaction network. Next, the Metascape database was utilized to enrich the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. In addition, Auto-Dock Vina software was used to verify drug and target binding. In total, 48 hub targets were obtained as the candidate targets responsible for DOP therapy. The anti-DOP effect mediated by XLGB was primarily centralized on the advanced glycation end products (AGEs)-receptor for AGE signaling pathway in diabetic complications and osteoclast differentiation. In addition, AKT serine/threonine kinase 1, tumor necrosis factor, Interleukin-6, vascular endothelial growth factor A and peroxisome proliferator activated receptor gamma, which were considered as potential therapeutic targets. Furthermore, molecular docking results confirm the credibility of the predicted therapeutic targets. This study elucidates that XLGB may through regulating AGEs formation and osteoclast differentiation as well as angiogenesis and adipogenesis against DOP. And this study provides new promising points to find the exact regulatory mechanisms of XLGB mediated anti-DOP effect.

Mechanism of Chaihuang-Yishen formula to attenuate renal fibrosis in the treatment of chronic kidney disease: Insights from network pharmacology and experimental validation

Renal fibrosis represents a pivotal characteristic of chronic kidney disease (CKD), for which effective interventions are currently lacking. The Src kinase activates the phosphatidylinositol-3 kinases (PI3K)/Akt1 pathway to promote renal fibrosis, casting a promising target for anti-fibrosis treatment. Chaihuang-Yishen formula (CHYS), a traditional Chinese medicinal prescription, has a validated efficacy in the treatment of CKD, however, with the underlying mechanism unresolved. This study aimed to uncover the pharmacological mechanisms mediating the effect of CHYS in treating renal fibrosis using network pharmacology followed by experimental validation. The chemical compounds of CHYS were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database or published literature, followed by the prediction of their targets using SwissTargetPrediction software. Disease (CKD/renal fibrosis)-related targets were retrieved from the Genecards database. Protein-protein interaction (PPI) network was generated using the drug-disease common targets and visualized in Cytoscape software. The drug-disease targets were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by Metascape software. Additionally, the compound-target-pathway network was established in Cytosape to identify key compounds, targets, and pathways. Network pharmacology analysis screened out 96 active compounds and 837 potential targets within the 7 herbal/animal medicines of CHYS, among which 237 drug-disease common targets were identified. GO and KEGG analysis revealed the enrichment of fibrosis-related biological processes and pathways among the 237 common targets. Compound-target-pathway network analysis highlighted protein kinases Src and Akt1 as the top two targets associated with the anti-renal fibrosis effects of CHYS. In UUO mice, treatment with CHYS attenuates renal fibrosis, accompanied by suppressed expression and phosphorylation activation of Src. Unlike Src, CHYS reduced Akt1 phosphorylation without affecting its expression. In summary, network pharmacology and in vivo evidence suggest that CHYS exerts its anti-renal fibrosis effects, at least in part, by inhibiting the Src/Akt1 signaling axis.