Mechanism Of Traditional Chinese Medicine Research Articles

Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study.

The purpose of this study is to investigate the potential mechanisms of Chinese herbs for the treatment of insomnia using a combination of data mining, network pharmacology, and molecular-docking validation. All the prescriptions for insomnia treated by the academician Qi Wang from 2020 to 2022 were collected. The Ancient and Modern Medical Case Cloud Platform v2.3 was used to identify high-frequency Chinese medicinal herbs and the core prescription. The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were utilized to predict the effective active components and targets of the core herbs. Insomnia-related targets were collected from 4 databases. The intersecting targets were utilized to build a protein-protein interaction network and conduct gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the STRING database, Cytoscape software, and clusterProfiler package. Gene chip data (GSE208668) were obtained from the Gene Expression Omnibus database. The limma package was applied to identify differentially expressed genes (DEGs) between insomnia patients and healthy controls. To create a "transcription factor (TF)-miRNA-mRNA" network, the differentially expressed miRNAs were entered into the TransmiR, FunRich, Targetscan, and miRDB databases. Subsequently, the overlapping targets were validated using the DEGs, and further validations were conducted through molecular docking and molecular dynamics simulations. Among the 117 prescriptions, 65 herbs and a core prescription were identified. Network pharmacology and bioinformatics analysis revealed that active components such as β-sitosterol, stigmasterol, and canadine acted on hub targets, including interleukin-6, caspase-3, and hypoxia-inducible factor-1α. In GSE208668, 6417 DEGs and 7 differentially expressed miRNAs were identified. A "TF-miRNA-mRNA" network was constructed by 4 "TF-miRNA" interaction pairs and 66 "miRNA-mRNA" interaction pairs. Downstream mRNAs exert therapeutic effects on insomnia by regulating circadian rhythm. Molecular-docking analyses demonstrated good docking between core components and hub targets. Molecular dynamics simulation displayed the strong stability of the complex formed by small molecule and target. The core prescription by the academician Qi Wang for treating insomnia, which involves multiple components, targets, and pathways, showed the potential to improve sleep, providing a basis for clinical treatment of insomnia.

Effects of butyrate on intestinal ischemia-reperfusion injury via the HMGB1-TLR4-MyD88 signaling pathway.

This study combined bioinformatics and experimental verification in a mouse model of intestinal ischemia-reperfusion injury (IRI) to explore the protection mechanism exerted by butyrate against IRI. GeneCards, Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine and GSE190581 were used to explore the relationship between butyrate and IRI and aging. Protein-protein interaction networks involving butyrate and IRI were constructed via the STRING database, with hub gene analysis performed through Cytoscape. Functional enrichment analysis was conducted on intersection genes. A mouse model of IRI was established, followed by direct arterial injection of butyrate. The experiment comprised five groups: normal, sham, model, vehicle, low-dose butyrate, and high-dose butyrate. Intestinal tissue observation was done via transmission electron microscopy (TEM), histological examination via hematoxylin and eosin (H&E) staining, tight junction proteins detection via immunohistochemistry, and Western blot analysis of hub genes. Drug-target interactions were evaluated through molecular docking. Butyrate protected against IRI by targeting 458 genes, including HMGB1 and TLR4. Toll-like receptor pathway was implicated. Butyrate improved intestinal IRI by reducing mucosal damage, increasing tight junction proteins, and lowering levels of HMGB1, TLR4, and MyD88. Molecular docking showed strong binding energies between butyrate and HMGB1 (-3.7 kcal/mol) and TLR4 (-3.8 kcal/mol). According to bioinformatics predictions, butyrate mitigates IRI via multiple-target and multiple-channel mechanisms. The extent of IRI can be reduced by butyrate through the inhibition of the HMGB1-TLR4-MyD88 signaling pathway, which is related to senescence.

Yantiao Formula intervention in Rats with Sepsis: Network Pharmacology and Experimental Analysis.

Traditional Chinese Medicine prescribes Yantiao Formula (YTF; peach kernel, mirabilite, Angelica sinensis, Radix Scrophulariae, raw rhubarb, Radix Paeoniae, Flos Lonicerae, Forsythia, and Ophiopogon japonicus) to treat sepsis. Clinically, it reduced the inflammatory response of sepsis. It also reduced lung damage by decreasing the level of TNF-α in septic rats' serum. Using network pharmacology analysis, we investigated the efficacy network and mechanism of YTF in treating sepsis. We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine (BATMAN-TCM) combined with literature to collect the main components in YTF and their targets. DisGeNET and GENECARDS databases were used for sepsis-related targets. Cytoscape 3.7.1 software was used to construct the herbcomponent- target and ingredient-target-disease interaction protein-protein interaction networks of YTF. The jvenn was used to perform the intersection of YTF targets and sepsis targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed． We also created a sepsis rat model using cecal ligation and perforation and stimulated alveolar macrophages (NR8383) with endotoxin to investigate the mechanisms of YTF. GO, and KEGG enrichment analysis revealed that these targets involved mineralocorticoid secretion, aldosterone secretion, active regulation of chronic inflammatory response, the exogenous coagulation pathway, and other pathophysiology. It was linked to various inflammatory factors and the MAPK pathway. YTF inhibits the p38MAPK pathway and decreases TNF- α, IL-6, and CXCL8 levels. YTF has a multi-component, multi-target, and multi-channel role in treating sepsis. The primary mechanisms may involve inhibiting the p38MAPK pathway to reduce the inflammatory response.

Study on the Mechanism of Competing Endogenous Network of 'Scutellaria barbata D.Don-Houttuynia cordata- Radix Scutellariae' in the Treatment of NSCLC based on Bioinformatics, Molecular Dynamics and Experimental Verification.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Traditional Chinese medicine, known for its multi-target and multi-pathway characteristics, offers a potential treatment approach for NSCLC. This study aimed to explore the mechanism of the competitive endogenous network of 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' in treating NSCLC through bioinformatics analysis and in vitro experiments. Various databases and ceRNA networks were utilized to collect and screen components and target genes, molecular docking and molecular dynamics simulations to determine the binding ability of ligand-receptor complexes. In vitro experiments were conducted to validate the effects of active ingredients of 'Scutellaria barbata D.Don-Houttuynia cordata- Radix Scutellariae' on non-small cell lung cancer cell line A549. The key target proteins CCL2, EDN1, MMP9, PPARG, and SPP1 were docked well with their corresponding TCM ligands. Among the ligand-receptor complexes, MMP9-Luteolin and MMP9-Quercetin demonstrated the weaking binding force, while the SPP1-Quercetin complex, associated with NSCLC prognosis, exhibited stable structure formation through hydrogen bond interaction during MD simulation. In vitro experiments confirmed the inhibitory effect of Quercetin on SPP1 expression, as well as the proliferation and migration of A549 cells. The findings suggest that 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' may potentially treat lung cancer by suppressing the expression of SPP1. This study provides valuable insights and novel research directions for understanding the mechanism of traditional Chinese medicine in combating lung cancer.

Clinical evidence and potential mechanisms of traditional Chinese medicine for refractory heart failure: a literature review and perspectives.

Refractory heart failure (RHF), or end-stage heart failure, has a poor prognosis and high case fatality rate, making it one of the therapeutic difficulties in the cardiovascular field. Despite the continuous abundance of methods and means for treating RHF in modern medicine, it still cannot meet the clinical needs of patients with RHF. How to further reduce the mortality rate and readmission rate of patients with RHF and improve their quality of life is still a difficult point in current research. In China, traditional Chinese medicine (TCM) has been widely used and has accumulated rich experience in the treatment of RHF due to its unique efficacy and safety advantages. Based on this, we comprehensively summarized and analyzed the clinical evidence and mechanism of action of TCM in the treatment of RHF and proposed urgent scientific issues and future research strategies for the treatment of RHF with TCM, to provide reference for the treatment of RHF.

Potential application mechanism of traditional Chinese medicine in treating immune checkpoint inhibitor-induced colitis.

Cancer ranks among the foremost causes of mortality worldwide, posing a significant threat to human lives. The advent of tumor immunotherapy has substantially transformed the therapeutic landscape for numerous advanced malignancies, notably non-small cell lung cancer and melanoma. However, as immune checkpoint inhibitors (ICIs) are increasingly applied in clinical settings, a spectrum of undesired reactions, termed immune-related adverse events (irAEs), has emerged. These adverse reactions are associated with immunotherapy and can result in varying degrees of harm to the human body. Among these reactions, Immune checkpoint inhibitor-induced colitis (ICIIC) stands out as one of the most prevalent clinical adverse events. In contemporary times, traditional Chinese medicine (TCM) has demonstrated remarkable efficacy in addressing various maladies. Consequently, investigating the potential application and mechanisms of Chinese medicine in countering immune checkpoint inhibitor-induced colitis assumes significant importance in the treatment of this condition.

Prediction of the Molecular Mechanism of Corni Fructus-Epimedii Folium- Rehmanniae Radix Praeparata in the Treatment of Postmenopausal Osteoporosis based on Network Pharmacology and Molecular Docking.

In this study, core drugs of clinical postmenopausal osteoporosis were retrieved using data mining, the drug molecular action target was predicted through network pharmacology, the key nodes of interaction were identified by combining postmenopausal osteoporosis-related targets, and the pharmacological mechanism of Traditional Chinese Medicine (TCM) against postmenopausal osteoporosis and other action mechanisms was explored. TCMISS V2.5 was used to collect TCM prescriptions of postmenopausal osteoporosis from databases, including Zhiwang, Wanfang, PubMed, etc., for selecting the highest confidence drugs. TCMSP and SwissTargetPrediction databases were selected to screen the main active ingredients of the highest confidence drugs and their targets. Relevant targets for postmenopausal osteoporosis were retrieved from GeneCards and GEO databases, PPI network diagrams construction and selection of core nodes in the network, GO and KEGG enrichment analysis, and molecular docking validation. Correlation analysis identified core drug pairs as 'Corni Fructus-Epimedii Folium- Rehmanniae Radix Praeparata' (SZY-YYH-SDH). After TCMSP co-screening and de-weighting, 36 major active ingredients and 305 potential targets were selected. PPI network graph was built from the 153 disease targets and 24 TCM disease intersection targets obtained. GO, KEGG enrichment results showed that the intersectional targets were enriched in the PI3K-Akt signalling pathway, etc. The target organs were mainly distributed in the thyroid, liver, CD33+_Myeloid, etc. Molecular docking results showed that the core active ingredients of the 'SZY-YYH-SDH' were able to bind to the pair core nodes and PTEN and EGFR. The results showed that 'SZY-YYH-SDH' can provide the basis for clinical application and treat postmenopausal osteoporosis through multi-component, multi-pathway, and multitarget effects.

Role of Pollution-Induced Oxidative Stress and Inflammation in Neurodegenerative Diseases, and the Mechanisms of Traditional Chinese Medicine’s Potential Remediation

Role of Pollution-Induced Oxidative Stress and Inflammation in Neurodegenerative Diseases, and the Mechanisms of Traditional Chinese Medicine’s Potential Remediation

Integration of meta-analysis and network pharmacology analysis to investigate the pharmacological mechanisms of traditional Chinese medicine in the treatment of hepatocellular carcinoma.

Background: This study will explore the therapeutic value of traditional Chinese medicine (TCM) in Hepatocellular Carcinoma (HCC) through meta-analysis, combined with network pharmacology analysis. Methods: The results of randomized controlled trials on TCM and HCC were retrieved and summarized from multiple databases. The effective active com-pounds and target genes of the high-frequency TCM were obtained using the TCMSP database, and disease targets of HCC were acquired through the public disease database. The network pharmacology analysis was used to get the core genes and investigate the potential oncogenic molecular mechanism. Results: A total of 14 meta-analysis studies with 1,831 patients suggested that therapy combined TCM is associated with better clinical efficacy and survival prognosis, as well as avoiding many adverse events. A total of 156 compounds, 247 herbal target genes and 36 core genes were identified. The function analysis suggested above genes may participate development in HCC through regulating some pathways, such as HIF-1 pathway and PD-L1 immune-related pathway. Conclusion: TCM, as a novel, safe, and effective multi-mechanism therapy, holds greater value in the treatment of HCC.

Identification of Hedyotisdiffusa Willd-specific mRNA–miRNA–lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification

Hedyotisdiffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA–miRNA–lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW’s regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA’s progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.

Qifu Yixin Formula Improves Heart Failure by Enhancing β-Arrestin2 Mediated the SUMOylation of SERCA2a.

This study aimed to elucidate the protective mechanism of Traditional Chinese Medicine (TCM) Qifu Yixin formula (QFYXF) to improve heart failure (HF) by promoting β-arrestin2 (β-arr2)-mediated SERCA2a SUMOylation. The transverse aortic constriction (TAC)-induced HF mice were treated with QFYXF or carvedilol for 8 weeks. β-arr2-KO mice and their littermate wild-type (WT) mice were used as controls. Neonatal rat cardiomyocytes (NRCMs) were used in vitro. Cardiac function was evaluated by echocardiography and serum NT-proBNP. Myocardial hypertrophy and myocardial fibrosis were assessed by histological staining. β-arr2, SERCA2a, SUMO1, PLB and p-PLB expressions were detected by Western blotting, immunofluorescence and immunohistochemistry. SERCA2a SUMOylation was detected by Co-IP. The molecular docking method was used to predict the binding ability of the main active components of QFYXF to β-arr2, SERCA2a, and SUMO1, and the binding degree of SERCA2a to SUMO1 protein. The HF model was constructed 8 weeks after TAC. QFYXF ameliorated cardiac function, inhibiting myocardial hypertrophy and fibrosis. QFYXF promoted SERCA2a expression and SERCA2a SUMOylation. Further investigation showed that QFYXF promoted β-arr2 expression, whereas Barbadin (β-arr2 inhibitor) or β-arr2-KO reduced SERCA2a SUMOylation and attenuated the protective effect of QFYXF improved HF. Molecular docking showed that the main active components of QFYXF had good binding activities with β-arr2, SERCA2a, and SUMO1, and SERCA2a had a high binding degree with SUMO1 protein. QFYXF improves HF by promoting β-arr2 mediated SERCA2a SUMOylation and increasing SERCA2a expression.

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.

Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology.

Placental syndromes, which include pregnancy loss, preterm birth, gestational diabetes mellitus (GDM), and hypertensive disorders in pregnancy (HDP), have a strong association with disorder inflammatory reactions. Nonetheless, the exact causal relationship has not been established. This study aims to investigate the causal relationship between placental syndromes and inflammatory cytokines utilizing Mendelian randomization (MR). Additionally, we examined the interaction between small molecular compounds derived from traditional Chinese medicine and inflammatory cytokines using molecular docking method. After obtaining the data of inflammatory cytokines and placental syndromes, as well as establishing single nucleotide polymorphisms (SNPs), we employed the inverse variance weighted (IVW) method to assess the causal relationship. We also accessed the heterogeneity and the horizontal pleiotropy of these data. The "ClusterProfiler" R package was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analyses. The protein-protein interaction (PPI) network was constructed using STRING database. AutoDock Vina software was used for molecular docking, and Discovery Studio 2019 was used for visualization purposes. We found that the growth regulated oncogene A (GROA) and interleukin-9 (IL-9) were associated with the development of pregnancy hypertension, whereas interleukin-10 (IL-10) and hepatocyte growth factor (HGF) were linked to the occurrence of preeclampsia. Moreover, there were correlations observed between interleukin-18 (IL-18), IL-10, macrophage colony-stimulating factor (MCSF), and platelet-derived growth factor BB (PDGFbb) in cases of chronic hypertension combined with pregnancy (CHP). Additionally, macrophage migration inhibitory factor (MIF) exhibited a connection with GDM, and TNF related apoptosis inducing ligand (TRAIL) demonstrated a causal relationship with preterm birth. It is plausible to suggest that interleukin-1β (IL-1β) might contribute to the promotion of pregnancy loss. All of the binding free energy values of small molecular compounds with inflammatory cytokines were below -5.0 kcal/mol. Furthermore, all of the RMSD values were less than 2. GROA, IL-1β, IL-9, IL-10, IL-18, MIF, MCSF, HGF, PDGFbb and TRAIL were found to be causally associated with placental syndromes. Molecular docking analysis revealed that small molecular compounds, such as puerarin, magnolol, atractylenolide I, paeoniflorin, tumulosic acid and wogonin, are closely bound to these inflammatory cytokines.

Application status and challenges of molecular docking in development of traditional Chinese medicine

Traditional Chinese medicine is precious treasure of ancient Chinese science and a key to unlocking the treasure trove of Chinese civilization. To elucidate the efficacy and mechanism of traditional Chinese medicines, scientists have been engaged in the research on the molecular basis and regulatory targets. Molecular docking is a computer-aided drug design method capable of visualizing the interaction between components and target proteins. With the progress in the modernization of traditional Chinese medicine and the advancement of algorithms and computing power, molecular docking has become an essential approach in the development of new traditional Chinese medicines. This article summarizes the recent research progress in molecular docking in the development of traditional Chinese medicine, aiming to provide valuable references for further screening of active components and offering insights for improving the development of new traditional Chinese medicines.

The potential mechanism of Aidi injection against neuroblastoma-an investigation based on network pharmacology analysis.

Background: Aidi injection, a classic traditional Chinese medicine (TCM) formula, has been used on a broader scale in treating a variety of cancers. In this study, we aimed to explore the potential anti-tumor effects of Aidi injection in the treatment of neuroblastoma (NB) using network pharmacology (NP). Methods: To elucidate the anti-NB mechanism of Aidi injection, an NP-based approach and molecular docking validation were employed. The compounds and target genes were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database. The protein-protein interaction network was constructed using the STRING database. clusterProfiler (R package) was utilized to annotate the bioinformatics of hub target genes. The gene survival analysis was performed on R2, a web-based genomic analysis application. iGEMDOCK was used for molecular docking validation, and GROMACS was utilized to validate molecular docking results. Furthermore, we investigated the anticancer effects of gomisin B and ginsenoside Rh2 on human NB cells using a cell viability assay. The Western blot assay was used to validate the protein levels of target genes in gomisin B- and ginsenoside Rh2-treated NB cells. Results: A total of 2 critical compounds with 16 hub target genes were identified for treating NB. All 16 hub genes could potentially influence the survival of NB patients. The top three genes (EGFR, ESR1, and MAPK1) were considered the central hub genes from the drug-compound-hub target gene-pathway network. The endocrine resistance and estrogen signaling pathways were identified as the therapeutic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gomisin B and ginsenoside Rh2 showed a good binding ability to the target protein in molecular docking. The results of cell experiments showed the anti-NB effect of gomisin B and ginsenoside Rh2. In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells. Conclusion: In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research.

Integration of 16 S rRNA gene sequencing, metabonomics and metagenome analysis to investigate the mechanism of Sparganium stoloniferum-Curcuma phaeocaulis in treating of endometriosis in rats

BackgroundEndometriosis is a gynecological disease that causes severe chronic pelvic pain and infertility in women. The therapeutic efficacy of the traditional herbal combination of Sparganium stoloniferum-Curcuma phaeocaulis (Sangleng-Ezhu, SL-EZ) in the treatment of endometriosis has been established. However, the precise mechanism by which this treatment exerts its effects remains elusive. MethodsTo gain further insights, UPLC-MS/MS was employed to identify the primary chemical constituents of SL-EZ in serum. Additionally, network pharmacology was utilized to analyze the active ingredients and their corresponding targets. Furthermore, the impact of SL-EZ on ectopic endometrial growth in endometrial implants was assessed using a rat model. The therapeutic mechanism of SL-EZ in rats with endometriosis was further investigated through the application of 16 S rRNA gene sequencing, metagenomic sequencing, and metabolomics. ResultsThe primary compounds in serum were zederone, p-coumaric acid, dehydrocostus lactone, curdione, curcumol. The growth of ectopic lesions in a rat model was effectively inhibited by SL-EZ. In comparison to the control group, the endometriotic rats exhibited a decrease in α-diversity of the gut microbiota, an increase in the Firmicutes/Bacteroidetes ratio, and a reduction in the abundance of Ruminococcaceae. Following SL-EZ intervention, the potential probiotic strains Lactobacillus gasseri and Lactobacillus johnsonii were able to restore the intestinal microenvironment at the species level. The altered metabolites were significantly correlated with Verrucomicrobia, Proteobacteria, and Bacteroidetes. The metabolomic analysis demonstrated significant alterations in intestinal metabolites. And SL-EZ intervention also exerted regulatory effects on various metabolic pathways in gut microbiota, including aminoacyl-tRNA biosynthesis, monobactam biosynthesis, cyanoamino acid metabolism, glycine, serine and threonine metabolism, plant secondary metabolite biosynthesis, and amino acid biosynthesis. ConclusionThe identification of novel treatment formulations for endometriosis was achieved through the utilization of network pharmacology and gut microbiota analyses. Our findings revealed simultaneous alterations in the microbiota within the rat model of endometriosis. The therapeutic efficacy of SL-EZ in treating endometriosis is attributed to its ability to restore the gut microbiota and regulate metabolism. This investigation offers valuable insights into the therapeutic mechanisms of traditional Chinese medicine (TCM) for endometriosis.

Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment.

Ferroptosis, distinct from apoptosis, is a novel cellular death pathway characterized by the build-up of lipid peroxidation and reactive oxygen species (ROS) derived from lipids within cells. Recent studies demonstrated the efficacy of ferroptosis inducers in targeting malignant cells, thereby establishing a promising avenue for combating cancer. Traditional Chinese medicine (TCM) has a long history of use and is widely used in cancer treatment. TCM takes a holistic approach, viewing the patient as a system and utilizing herbal formulas to address complex diseases such as cancer. Recent TCM studies have elucidated the molecular mechanisms underlying ferroptosis induction during cancer treatment. These studies have identified numerous plant metabolites and derivatives that target multiple pathways and molecular targets. TCM can induce ferroptosis in tumor cells through various regulatory mechanisms, such as amino acid, iron, and lipid metabolism pathways, which may provide novel therapeutic strategies for apoptosis-resistant cancer treatment. TCM also influence anticancer immunotherapy via ferroptosis. This review comprehensively elucidates the molecular mechanisms underlying ferroptosis, highlights the pivotal regulatory genes involved in orchestrating this process, evaluates the advancements made in TCM research pertaining to ferroptosis, and provides theoretical insights into the induction of ferroptosis in tumors using botanical drugs.

Network pharmacology and molecular docking approach to investigate the mechanism of a Chinese herbal formulation Yougui pills against steroid-related osteonecrosis of the femoral head

Yougui pills (YGPs) is a classical prescription formula for treating steroid-related osteonecrosis of the femoral head (SONFH) in traditional Chinese medicine (TCM). However, its key ingredients and mechanisms of action are still unknown. In the study, we used molecular docking and network pharmacology to comprehensively investigate the mechanism by YGPs impact on SONFH. TCMSP was used to identify the effective active components of YGPs. Targets associated with SONFH were extracted from GEO datasets in conjunction with GeneCards, OMIM, and DisGeNET databases. Protein-protein interaction (PPI) networks were built using the intersection targets by importing them into the STRING database. Furthermore, DAVID was used to conduct a pathway enrichment analysis for both GO and KEGG. Finally, molecular docking and molecular dynamics simulation was performed to verify the binding ability between key targets and active compound. Screening using relevant databases revealed 126 active compounds with 1078 targets in YGPs, mainly including helenalin, quercetin, stigmasterol, sesamin, etc. The topological analysis of the PPI network revealed that key targets included VEGFA, IL6, IL1B, TNF, ALB, and TP53. According to the findings of the GO enrichment analysis, genes were most significantly enriched in the inflammatory response, response to hypoxia, and positive regulation of angiogenesis. The effects of YGPs have been mostly linked to the HIF-1 signaling pathway and the PI3K-Akt signaling pathway, according to a KEGG pathway enrichment analysis. In addition, the results of molecular docking and molecular dynamics simulations demonstrated that the active chemicals in YGPs have high affinity with the relevant targets. This investigation integrates molecular docking and network pharmacology to identify the effective compounds, related targets, and potential mechanism of YGPs in the treatment of SONFH. This research may provide an integrative strategy to clarify the pharmacological mechanisms of traditional Chinese medicines.

Multi-technology integrated network pharmacology-based study on phytochemicals, active metabolites, and molecular mechanism of Psoraleae Fructus to promote melanogenesis

Ethnopharmacological relevanceAccording to the Compendium of Materia Medica (Shizhen Li, Ming dynasty) and Welfare Pharmacy (Song dynasty), Psoraleae Fructus (PF), a traditional Chinese medicine (TCM) has a bitter taste and warm nature, which has the effect of treating spleen and kidney deficiency and skin disease. Although PF has been widely used since ancient times and has shown satisfactory efficacy in treating vitiligo, the active substances and the mechanism of PF in promoting melanogenesis remain unclear. Aim of the studyTo explore the active substances and action mechanisms of PF in promoting melanogenesis. Materials and methodsFirstly, UPLC-UV-Q-TOF/MS was used to characterize the components in PF extract and identify the absorption components and metabolites of PF after oral administration at usual doses in rats. Secondly, the active substances and related targets and pathways were predicted by network pharmacology and molecular docking. Finally, pharmacodynamic and molecular biology experiments were used to verify the prediction results. ResultsThe experimental results showed that 15 compounds were identified in PF extract, and 44 compounds, consisting of 8 prototype components and 36 metabolites (including isomers) were identified in rats' plasma. Promising action targets (MAPK1, MAPK8, MAPK14) and signaling pathways (MAPK signaling pathway) were screened and refined to elucidate the mechanism of PF against vitiligo based on network pharmacology. Bergaptol and xanthotol (the main metabolites of PF), psoralen (prototype drug), and PF extract significantly increased melanin production in zebrafish embryos. Furthermore, bergaptol could promote the pigmentation of zebrafish embryos more than psoralen and PF extract. Bergaptol significantly increased the protein expression levels of p-P38 and decreased ERK phosphorylation in B16F10 cells, which was also supported by the corresponding inhibitor/activator combination study. Moreover, bergaptol increased the mRNA expression levels of the downstream microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells. Our data elucidate that bergaptol may promote melanogenesis by regulating the p-P38 and p-ERK signaling pathway. ConclusionsThis study will lay a foundation for discovering potential new drugs for treating vitiligo and provide feasible ideas for exploring the mechanism of traditional Chinese medicine.

A novel enzyme-based functional correlation algorithm for multi-omics reveals the potential mechanisms of traditional Chinese medicines: Taking Jian-Pi-Yi-Shen formula as an example

The integrated analysis of host metabolome and intestinal microbiome is an opportunity to explore the complex therapeutic mechanisms of traditional Chinese medicines. Currently, researchers mainly employ various statistical correlation analytical methods to investigate metabolome-microbiome correlations. However, these conventional correlation techniques often focus on statistical correlations and their biological meanings are always ignored, especially the functional relevance between them. Here, we developed a novel enzyme-based functional correlation (EBFC) algorithm to further improve the interpretability and the identified scope of microbe-metabolite correlations based on the conventional Spearman’s analysis. The proposed EBFC algorithm is successfully utilized to reveal the therapeutic mechanisms of Jian-Pi-Yi-Shen (JPYS) formula on the treatment of adenine-induced chronic kidney disease (CKD) rats. JPYS, a TCM formula for treating CKD, has beneficial clinical effects. We tentatively revealed the potential mechanism of JPYS for treating CKD rats from the perspective of the serum metabolome, gut microbiome, and their interactions. Specifically, 11 metabolites and 19 bacterial genera in the CKD rats were significantly regulated to approaching normal status after JPYS treatment, suggesting that JPYS could ameliorate the pathological symptoms of CKD rats by reshaping the disturbed metabolome and gut microbiota. Further correlation analysis between the significantly perturbed metabolites, microbiota, and the related enzymes provided more strong evidence for the study of host metabolism-microbiota interactions and the therapeutic mechanism of JPYS on CKD rats. In conclusion, these findings will help us to deeply understand the pathogenesis of CKD and provide new insights into the therapeutic mechanism of JPYS.