Mechanism Of Traditional Chinese Medicine Research Articles

Mechanistic insights into pachymic acid’s action on triple-negative breast Cancer through TOP2A targeting

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and lack of human epidermal growth factor receptor 2 (HER2) expression. Traditional Chinese medicine (TCM) has demonstrated promising efficacy in treating TNBC. This study explored the mechanisms of pachymic acid (PA) on TNBC by merging network pharmacology with experimental validation. We acquired Microarray data of TNBC from the Gene Expression Omnibus (GEO). The related targets of PA were predicted and screened using the following 6 databases: Swiss Target Prediction, HERB (Herbal Medicine Database), ETCM (Encyclopedia of Traditional Chinese Medicine), BATMAN (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine), HIT (Herb Ingredients’ Targets Database), and PharmMapper. The STRING interaction network analysis tool was used to create Protein-Protein Interaction (PPI) networks. Enrichment analysis included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We conducted a pan-cancer analysis, tumor immune microenvironment analysis, and molecular docking. We performed cell experimental, included cytotoxicity assay, apoptosis analysis, proliferation assay, and migration and invasion assays. PA has potential for treating TNBC with the target of TOP2A, and platinum drug resistance possibly serving as the KEGG pathway through which PA exerts its therapeutic effects. PA is involved in processes such as nuclear division, chromosome segregation, mitotic nuclear division, condensed chromosome formation, and protein C-terminus binding. PA probably exert its therapeutic effects through the tumor immune microenvironment, involving elements such as Dendritic cells activated, Eosinophils, Macrophages M0, Macrophages M1, and T cells CD4 memory activated. The therapeutic effects of PA may vary across different subtypes of TNBC such as TNBC-BL1, TNBC-Metaplastic, and TNBC-BL2. This study provides compelling evidence that PA holds significant promise as a therapeutic agent for TNBC, primarily through its action on TOP2A and its influence on the TNBC.

Advanced Carriers for Precise Delivery and Therapeutic Mechanisms of Traditional Chinese Medicines: Integrating Spatial Multi-Omics and Delivery Visualization.

The complex composition of traditional Chinese medicines (TCMs) has posed challenges for in-depth study and global application, despite their abundance of bioactive compounds that make them valuable resources for disease treatment. To overcome these obstacles, it is essential to modernize TCMs by focusing on precise disease treatment. This involves elucidating the structure-activity relationships within their complex compositions, ensuring accurate in vivo delivery, and monitoring the delivery process. This review discusses the research progress of TCMs in precision disease treatment from three perspectives: spatial multi-omics technology for precision therapeutic activity, carrier systems for precise in vivo delivery, and medical imaging technology for visualizing the delivery process. The aim is to establish a novel research paradigm that advances the precision therapy of TCMs.

Therapeutic potential and pharmacological mechanisms of Traditional Chinese Medicine in gout treatment.

Gout is a systemic metabolic disorder caused by elevated uric acid (UA) levels, affecting over 1% of the population. The most common complication of gout is gouty arthritis (GA), characterized by swelling, pain or tenderness in peripheral joints or bursae, which can lead to the formation of tophi. At present, western medicines like colchicine, febuxostat and allopurinol are the primary treatment strategy to alleviate pain and prevent flare-ups in patients with GA, but they have significant side effects and increased mortality risks. Traditional Chinese medicine (TCM) has been utilized for thousands of years for the prevention and treatment of GA, demonstrating effective control over serum UA (SUA) levels with fewer side effects. Herein we summarized a total of 541 studies published from 2000 to 2023 in sources including PubMed, Web of Science, the Cochrane Library and Embase, highlighting the therapeutic potential of TCM in treating gout and GA, particularly in combination with modern medical strategies. This review focuses on TCM formulas, Chinese herbal extracts, and active compounds derived from TCM, providing an overview of recent clinical application and the pharmacological research based on animal models and cellular systems. Particularly, the current review categorized the clinical and experimental evidence into the strategies for improving hyperuricemia, decreasing the sudden onset of acute GA and retarding chronic GA progression, supplied further coherent reference and enlightenment for clinicians, investigators of natural product chemistry, researchers in TCM and pharmacology. We hope this article will inspire the development of novel formulas and molecular entities for the treatment of gout and GA.

Network pharmacology: Changes the treatment mode of "one disease-one target" in cancer treatment.

The article concluded that network pharmacology provides new ideas and insights into the molecular mechanism of traditional Chinese medicine (TCM) treatment of cancer. TCM is a new choice and hot spot in the field of cancer treatment. We have also previously published studies on TCM and network pharmacology. In this letter, we summarize the new paradigm of network pharmacology in cancer treatment mechanisms.

The Exploration of TCM Therapeutic Mechanism as Evidenced by Houpusanwu Decoction on GI Disorders Treatment using Systems Pharmacology

Background: Gastrointestinal (GI) disorders are a kind of common, but complicated disease that may be triggered by many factors. In Asia, many traditional Chinese herbs are prominent in treating GI disorders, but the pharmacological mechanism still remains vague or unknown due to the multiple-component characteristics of traditional Chinese medicine (TCM). Objective: In order to investigate the therapy mechanism of traditional Chinese medicine (TCM) for Gastrointestinal (GI) diseases, a typical TCM prescription, Houpusanwu Decoction, for the treatment of ileus, a severe GI disease, is used as a probe presently. Method: We performed data mining on all components in Houpusanwu Decoction (HD), established a corresponding component database, and then conducted ADME screening of potentially active compounds in the database. Next, we identify potential targets of HD candidate compounds, followed by the establishment of a series of pharmacological networks. Finally, we conducted SP analysis and mechanism analysis. Results: Through pathway analysis, we found that HD treats ileus mainly through four pathways, i.e., GI motility-related Calcium, inflammation-related SCF/c-kit and p38/MAPK, and thrombosis and diabetes-related JAK2/STAT3 signaling pathways, which indicated that HD is a typical prescription with multichannel and multifunction of TCM characteristics. Conclusion: This study not only expounds the pathogenesis of ileus and, at the same time systematically illuminates the curative mechanism of HD, but also provides a novel SP method to explore the therapeutic mechanism of TCM in treating complicated GI diseases.

Traditional Chinese Medicine for Liver Cancer Treatment: Network Pharmacology Research.

As one of the common malignant tumors nowadays, liver cancer has more risk factors for its development and is characterized by a high recurrence rate, high mortality rate, and poor prognosis, which poses a great threat to people's health. The specific efficacy of traditional Chinese medicine is based on clinical practice, which is a high degree of generalization of the characteristics and scope of the clinical effects of prescription medicines and a special form of expression of the medical effects of the human body within the scope of traditional Chinese medicine. Because of its multi-ingredient, multi-target, and multi-pathway characteristics, it has a great advantage in the treatment of liver cancer. Still, at present, its specific molecular mechanism of action has not yet been clarified. This study reviews the current status and characteristics of network pharmacology research in the treatment of liver cancer, aiming to provide new ideas and methods for traditional Chinese medicine treatment of the disease. This study was searched on the Web of Science and PubMed using keywords, such as "traditional Chinese medicine", "liver cancer," and "network pharmacology." The citation dates of the literature cited in this review are from 2000 to 2024. The discovery of the key molecular mechanisms of traditional Chinese medicine in the treatment of liver cancer through the network pharmacology approach and the in-depth study of the related signaling pathways are conducive to a more in-depth exploration of traditional Chinese medicine. Network pharmacology research plays a key role in the treatment and prevention of liver cancer and deserves deeper exploration in the future.

Exploring the molecular mechanism of Taohong Siwu decoction in the treatment of non-small-cell lung cancer based on network pharmacology and molecular docking.

This study aimed to explore the mechanism of Taohong Siwu decoction (THSWD) in the treatment of non-small-cell lung cancer (NSCLC) by using comprehensive analysis. The active components and relevant targets of THSWD were analyzed by network analysis to construct the active component-target-disease network diagram. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted on the core targets by the Metascape database. Molecular docking verification was used for molecular visualization. A total of 69 active compounds and 114 targets were filtered in lung cancer treatment with THSWD. KEGG analysis suggested that tumor necrosis factor (TNF) signaling pathway, and apoptosis pathway played critical roles. The results of molecular docking showed that populoside_qt with IL-6, baicalein with epidermal growth factor receptor (EGFR), and luteolin with MAPK8 had the strongest binding ability. Moreover, experiment validation revealed that THSWD regulated the expression of IL-6, AKT, Cyclin D1, E-cadherin, and LC3A/B, thereby inhibiting the proliferation and migration ability, promoting apoptosis, and blocking the cell cycle of NSCLC cells. The potential targets and molecular mechanisms of THSWD in the treatment of NSCLC were preliminarily revealed by a comprehensive analysis in this study, which will provide new ideas and methods for the study of the mechanism of traditional Chinese medicine in treating lung cancer.

Piceatannol-3'-O-β-D-glucopyranoside inhibits neuroexcitotoxicity and ferroptosis through NMDAR/NRF2/BACH1/ACSL4 pathway in acute ischemic stroke.

Neuronal protection is a well-established method of acute ischemic stroke (AIS) treatment. The pharmacodynamic effect of Piceatannol-3'-O-β-D-glucopyranoside (Chinese name: Quzhazhigan, QZZG) on AIS has been reported, but the molecular mechanism of this effect remains unknown. The purpose of this study is to elucidate the pharmacodynamic effects and mechanisms of QZZG in the treatment of AIS. A combined network pharmacology and metabolomics approach was used to predict the key targets and pathways of QZZG in the treatment of AIS and to elucidate the mechanism of QZZG through experimental validation. In this study, QZZG improved histopathologic features and reduced infarct volume and neurologic deficit scores. Integrated network pharmacology and metabolomics revealed that QZZG may protect neurons by regulating glutamate and its receptors, and that glutamate is closely related to NMDAR1, NRF2, and Caspase-3. Pathway analysis results suggested that NMDAR-mediated Ca2+ inward flow is one of the critical pathways. In terms of neuroexcitotoxicity QZZG inhibited glutamate content, reduced Ca2+ inward flow, protected mitochondrial function, and reduced ROS, as well as being able to effectively inhibit the expression of NMDAR1, Caspase-3, Bax, and promote the expression of Bcl-2, NMDAR2A. In terms of ferroptosis QZZG promoted NRF2, HO-1, GPX4 and nuclear-NRF2, inhibited the expression of BACH1 and ACSL4, and suppressed Fe2+ accumulation and lipid peroxidation. Silencing of BACH1 resulted in elevated expression of NRF2 and decreased expression of ACSL4, which inhibited the sensitivity of neurons to ferroptosis. QZZG was able to further increase NRF2 expression under conditions of silencing BACH1. QZZG induced NRF2 and inhibited BACH1, ACSL4 was inhibited by ML385, and inhibition of NRF2 induced the expression of BACH1 and ACSL4, QZZG protects neurons in an NRF2-dependent manner. In summary, QZZG inhibited neuroexcitotoxicity and ferroptosis by regulating the NMDAR/NRF2/BACH1/ACSL4 pathway. The study provided a relatively novel perspective on the mechanism of traditional Chinese medicine (TCM) treatment of the disease.

Network Pharmacology and In Vivo Experimental Verification of the Mechanism of the Qing'e Pill for Treating Intervertebral Disc Degeneration.

The Qing'e Pill (QEP) is widely used to alleviate low back pain and sciatica caused by Intervertebral Disc Degeneration (IDD). However, its active components, key targets, and molecular mechanisms are not fully understood. The aim of this study is to elucidate the molecular mechanisms through which the QEP improves IDD using database mining techniques. Active components and candidate targets of the QEP were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine. IDD-related targets were obtained from the GeneCards database, and liver- and kidney-specific genes were retrieved from the BioGPS database. The intersection of these candidate targets was analyzed to identify potential targets for the QEP in IDD. A protein-protein interaction network analysis was performed using STRING and Cytoscape 3.7.2 software. Core targets were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to assess the binding affinity of active components to candidate targets, and animal experiments were conducted for validation. We identified 65 potentially active components of the QEP that corresponded to 1,093 candidate targets, 2,108 IDD-related targets, and 1,113 liver- and kidney-specific genes. Key components included quercetin, berberine, isorhamnetin, and emodin. The primary candidate targets were Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3. The GO and KEGG analyses revealed the involvement of these targets in Wnt signaling, TNF signaling, Wnt receptor activation, Frizzled binding, and Wnt-protein interactions. Molecular docking showed strong binding between these components and their targets. Animal experiments demonstrated that the QEP treatment significantly reduced the expression of Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3 at high, medium, and low doses compared with the model group. The QEP alleviated IDD by modulating the Wnt/MAPK/MMP signaling pathways and reducing the release and activation of key factors.

Mechanism of traditional Chinese medicine in treating vascular calcification in chronic kidney disease based on BMP and SIRT signaling pathways

Vascular calcification significantly increases the incidence of cardiovascular disease and all-cause mortality patients with chronic kidney disease(CKD), severely affecting their health and lifespan. However, the mechanisms underlying vascular calcification in CKD remain incompletely understood, and the available therapeutic agents are limited. Research has found that the transformation of vascular smooth muscle cells(VSMCs) from a contractile phenotype to an osteoblast-like phenotype is a key step in CKD-related vascular calcification. As research on the pathogenesis of calcification progresses, it has been demonstrated that bone morphogenetic protein(BMP) and silent information regulator(SIRT) signaling pathways can participate in the process of vascular calcification by regulating the osteogenic transdifferentiation of VSMCs. Traditional Chinese medicine(TCM) has accumulated a wealth of valuable experience in the prevention and treatment of kidney diseases over centuries. Modern research indicates that TCM, with its multi-pathway, multi-target, and low-toxicity properties, has shown certain advantages in the prevention and treatment of CKD-related vascular calcification and in improving patients' quality of life. Therefore, in this study, we will introduce the latest research progress of TCM in preventing and treating CKD-related vascular calcification, particularly focusing on the BMP and SIRT signaling pathways, with the aim of providing ideas for the clinical diagnosis and treatment of CKD-related vascular calcification with TCM and related basic research.

Evaluation of the Potential Targets of Shenxian-Shengmai Oral Liquid in Treating Sick Sinus Syndrome Based on Network Pharmacology and Molecular Docking.

Shenxian-Shengmai (SXSM) is a Chinese patent medicine used in the treatment of sick sinus syndrome (SSS). However, its active chemical compounds and the underlying molecular mechanisms remain unclear. In this study, we researched the underlying mechanisms of SXSM in treating SSS. We conducted network analysis and molecular docking to identify the small molecules and core targets responsible for the therapeutic efficacy of SXSM on SSS. Invitro experiments were performed to verify the potential therapeutic mechanism. Network pharmacological analysis identified 17 core targets. Among these, BMP4, KCNH2, KCNMA1, and KCNQ1 were identified to be involved in various biological processes, such as the formation and regulation of the cardiac pacemaking system and potassium ion transmembrane transport. The experimental analysis revealed that SXSM could upregulate the expression of the Bmp4/Tbx3/Hcn4 pathway and the expression of Kcnh2, Kcnma1, and Kcnq1 channels, which protected and improved the pacemaking function of pacemaker cells (P cells) and increased the heart rate. These findings provide a scientific basis in the study of the mechanism of traditional Chinese medicine in the treatment of SSS.

Anti-tumor mechanism of traditional Chinese medicine via Hedgehog signaling pathway: a review

The Hedgehog(Hh) signaling pathway has the functions of improving embryogenesis and maintaining tissue homeostasis. By influencing the tumor microenvironment, intervening in cell apoptosis, and regulating angiogenesis, it is pivotal in the occurrence, progression, and recovery of various tumors. Therefore, targeting and inhibiting the abnormal activation of the Hh pathway has become a potential research strategy for alleviating and treating cancer. Currently, traditional Chinese medicine(TCM) is highly favored for treating cancer and other challenging and severe diseases due to its advantages, such as minimal side effects, high efficacy, lack of dependency, and the ability to address both symptoms and underlying causes. This review aimed to provide a scientific foundation and research ideas for the prevention and treatment of cancer with TCM by summarizing and reviewing the correlation between the Hh pathway and tumors, as well as the feasibility of using TCM to modulate the Hh pathway for anti-tumor effects.

Research progress on indirect action and mechanism of traditional Chinese medicine based on gut-gut microbiota-target organ talks

Traditional Chinese medicine(TCM) has been treating diseases for thousands of years and still holds an irreplaceable position in modern disease treatment. The composition of TCM is complex, and its mode of action features multi-pathway and multi-target characteristics, making its pharmacological actions and mechanisms complicated. The principles and mechanisms of TCM have always been a hot topic among scholars from various fields. Increasingly, studies show that indirect action plays an important role in the mode of action of TCM. The gut microbiota is regarded as a new invisible metabolic organ, and TCM can treat diseases by targeting the gut microbiota, thereby exerting an indirect effect across organs based on the connection between organs. Therefore, this paper summarized the indirect regulatory mechanisms of TCM based on the visceral manifestation theory and the organ axis of modern medical research. It also discussed the talks and communication mechanisms between the gut microbiota and target organs such as the liver, brain, kidney, and lungs, providing references for research on the mechanisms of indirect action of TCM and the development of innovative drugs.

Integrative multi-omics and network pharmacology reveal the mechanisms of Fangji Huangqi Decoction in treating IgA nephropathy

Ethnopharmacological relevanceFangji Huangqi Decoction (FJHQD), a classical Chinese herbal formulation, has demonstrated significant clinical efficacy in the treatment of IgA nephropathy (IgAN), although its mechanisms remain poorly understood. Aim of the studyThis study aims to investigate the renal protective mechanisms of FJHQD using an integrated approach that combines transcriptomics, proteomics, and network pharmacology. MethodsRenal glomerular structure changes were assessed via hematoxylin and eosin (H&E) and Masson staining. IgA expression in the glomeruli was quantified using immunofluorescence. Furthermore, the potential mechanisms underlying the effects of FJHQD were explored through a combined strategy of network pharmacology, transcriptomics, and proteomics. The expression of signaling pathway-related proteins was detected using Western blot. ResultsFJHQD inhibited mesangial cell proliferation and renal interstitial fibrosis, and significantly reduced excessive IgA deposition in the glomerular mesangium. Network pharmacology identified 113 important active components and 8 common active components in FJHQD, with quercetin, isorhamnetin, jaranol, and kaempferol having the highest number of target interactions. Integration of network pharmacology with multi-omics approaches revealed that 44 active components regulated numerous immune and inflammatory signaling pathways through 17 hub targets. These pathways include the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. Subsequent in vivo experiments demonstrated that FJHQD effectively regulates the identified pathways in IgAN mice. Ultimately, molecular docking results further validated the reliability of the network pharmacology combined with multi-omics analyses. ConclusionThe findings suggest that FJHQD exerts a renal protective effect, potentially through modulation of the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. These insights offer valuable support for the clinical use of FJHQD and open new avenues for exploring the active compounds and molecular mechanisms of Traditional Chinese Medicines (TCMs).

A Mendelian analysis of the causality between inflammatory cytokines and digestive tract cancers.

In this study, we performed a two-sample Mendelian randomization (MR) analysis to assess the causality between inflammatory cytokines and the risk of digestive tract cancers (DTCs). Furthermore, we conducted a molecular docking study to predict the therapeutic mechanisms of traditional Chinese medicine (TCM) compounds in the treatment of DTCs. In our MR analysis, genetic variations associated with eight types of DTCs were utilized, which were sourced from a large publicly available genome-wide association study dataset (7929 cases and 1 742 407 controls of European ancestry) and inflammatory cytokines data from a genome-wide association study summary of 8293 European participants. Inverse-variance weighted method, MR-Egger, and weighted median were performed to analyze and strengthen the final results. We investigated the effects of 41 inflammatory molecules on 8 types of DTCs. Subsequently, the effect of DTCs on positive inflammatory factors was analyzed by means of inverse MR. Molecular docking was exploited to predict therapeutic targets with TCM compounds. Interleukin-7, interleukin-16, macrophage colony-stimulating factor, monokine induced by interferon-gamma, and vascular endothelial growth factor may be significantly associated with various types of DTCs. Five TCM compounds (baicalin, berberine, curcumin, emodin, and salidroside) demonstrated better binding energies to both interleukin-7 and vascular endothelial growth factor than carboplatin. This study provides strong evidence to support the potential causality of some inflammatory cytokines on DTCs and indicates the potential molecular mechanism of TCM compounds in the treatment of DTCs. Key message What is already known on this topic The increasing evidence indicates that inflammatory cytokines are implicated in the pathogenesis of digestive tract cancers (DTCs). Nevertheless, the causal relationship between inflammatory cytokines and DTCs remains indistinct. Additionally, certain traditional Chinese medicine compounds have been demonstrated to treat DTCs by influencing inflammatory factors, yet their underlying potential mechanisms remain ambiguous. What this study adds In this study, Mendelian randomization analysis was performed for the first time regarding the causality between human inflammatory cytokines and eight types of DTCs, which revealed that inflammatory factors may play different roles in different types of DTCs. Moreover, molecular docking of key inflammatory factors was implemented, indicating the targets for drug actions. How this study might affect research, practice, or policy This research has the potential to reveal the causality between 41 inflammatory factors and 8 DTCs, offering novel perspectives for the prevention and management strategies of DTCs. Additionally, it indicates the targets for the actions of traditional Chinese medicine on the key inflammatory factors of these cancers.

Pachymic acid promotes ferroptosis and inhibits gastric cancer progression by suppressing the PDGFRB-mediated PI3K/Akt pathway

Gastric cancer (GC) is a common malignant tumour with high incidence and mortality rates worldwide. Despite current treatment modalities, including surgical resection and chemotherapy, challenges such as postoperative recurrence, metastasis and drug resistance persist. Therefore, investigating the feasibility and mechanism of traditional Chinese medicine in treating gastric cancer is crucial for discovering new anti-gastric cancer drugs or adjuvant therapies. Pachymic acid (PA) is a natural triterpenoid found in the traditional Chinese medicinal herb Poria cocos (PC) (Schw. Wolf). Recent studies have reported its inhibitory effects on various cancer cells, including liver, cervical, breast and gastric cancer. Our in vitro and in vivo experiments confirmed that PA inhibits the proliferation, migration and invasion of gastric cancer cells. The treatment of gastric cancer cells with various death inhibitors revealed that PA may suppress gastric cancer progression by inducing ferroptosis. Malondialdehyde, Fe2+, reactive oxygen species and glutathione assays were performed to validate the effects of PA on ferroptosis in gastric cancer. High-throughput sequencing combined with analysis of the TCGA database identified PDGFRB as a potential downstream target of PA. In vivo experiments indicated that the PDGFRB overexpression could counteract the antitumour effects of PA, while ferroptosis induced by the PI3K/Akt signalling pathway may play a key role in this process. This study provides initial evidence that PA, through its interaction with PDGFRB, alters the PI3K/Akt signalling pathway, leading to ferroptosis in gastric cancer cells, thus manifesting its antitumour properties. This discovery holds promise for the development of novel therapeutic strategies for gastric cancer patients.

Exploring the potential mechanism of Radix Bupleuri in the treatment of sepsis: a study based on network pharmacology and molecular docking

AimTo explore, using network pharmacology and RNA-seq technologies, potential active targets and mechanisms underpinning Radix Bupleuri’s effectiveness during sepsis treatment.MethodsFollowing the Sepsis-3.0 criteria, the research cohort, comprising 23 sepsis patients and 10 healthy participants, was obtained from public databases. Peripheral blood samples were collected and subjected to RNA-seq analysis. Active ingredients and potential targets of Radix Bupleuri were identified using the Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine 2.0 (BATMAN-TCM 2.0) database and TCMSP database. Subsequently, protein-protein interaction (PPI) network construction, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted to explore cross-targets between disease and drugs. Survival analysis of key targets was performed using the GSE65682 dataset, and single-cell RNA-seq was employed for cellular localization analysis of key genes. Finally, molecular docking and Molecular dynamics simulation of the core target was conducted.ResultsDifferential expression analysis revealed 4253 genes associated with sepsis. Seventy-six active components and 1030 potential targets of Radix Bupleuri were identified. PPI, GO, and pathway enrichment analyses indicated involvement in the regulation of transmembrane transport, monatomic ion transport, and MAPK signaling. Survival curve analysis identified PIK3CD, ARRB2, SUCLG1, and SPI1 as key targets associated with lower mortality in the high expression group, while higher mortality was observed in the high PNP and FURIN expression groups. Single-cell RNA sequencing unveiled the cellular localization of PIK3CD, PNP, SPI1, and FURIN within macrophages, while ARRB2 and SUCLG1 exhibited localization in both macrophages and T-cells. Subsequent molecular docking and Molecular dynamics simulation indicated a potential binding interaction for Carvone-PIK3CD, Encecalin-ARRB2, Lauric Acid-SUCLG1, Pulegone-FURIN, Nootkatone-SPI1, and Saikogenin F-PNP.ConclusionRadix Bupleuri could modulate immune function by affecting PIK3CD, ARRB2, SUCLG1, FURIN, SPI1, and PNP, thereby potentially improving the prognosis of sepsis.

A Dataset for Constructing the Network Pharmacology of Overactive Bladder and Its Application to Reveal the Potential Therapeutic Targets of Rhynchophylline

Objectives: Network pharmacology is essential for understanding the multi-target and multi-pathway therapeutic mechanisms of traditional Chinese medicine. This study aims to evaluate the influence of database quality on target identification and to explore the therapeutic potential of rhynchophylline (Rhy) in treating overactive bladder (OAB). Methods: An OAB dataset was constructed through extensive literature screening. Using this dataset, we applied network pharmacology to predict potential targets for Rhy, which is known for its therapeutic effects but lacks a well-defined target profile. Predicted targets were validated through in vitro experiments, including DARTS and CETSA. Results: Our analysis identified Rhy as a potential modulator of the M3 receptor and TRPM8 channel in the treatment of OAB. Validation experiments confirmed the interaction between Rhy and these targets. Additionally, the GeneCards database predicted other targets that are not directly linked to OAB, corroborated by the literature. Conclusions: We established a more accurate and comprehensive dataset of OAB targets, enhancing the reliability of target identification for drug treatments. This study underscores the importance of database quality in network pharmacology and contributes to the potential therapeutic strategies for OAB.

Ferroptosis: a new mechanism of traditional Chinese medicine for treating hematologic malignancies.

Ferroptosis is a recently identified form of cell death characterized by lipid peroxidation and elevated iron levels. It is closely associated with hematologic malignancies, including leukemia, multiple myeloma (MM), and myelodysplastic syndromes (MDS). Research indicates that ferroptosis could represent a novel therapeutic target for these hematologic malignancies. Furthermore, traditional Chinese medicine (TCM) has been shown to modulate hematologic malignancies through the ferroptosis pathway. This paper aims to elucidate the mechanisms underlying ferroptosis and summarize the current research advancements regarding ferroptosis in hematologic malignancies, as well as the role of traditional Chinese medicine in the prevention and treatment of ferroptosis, with the goal of enhancing treatment efficacy.

The regulatory effect and mechanism of traditional Chinese medicine on the renal inflammatory signal transduction pathways in diabetic kidney disease: A review.

Inflammatory injury is a critical factor in the occurrence and development of diabetic kidney disease (DKD). Signal transduction pathways such as the nuclear factor kappa beta (NF-κB), mitogen-activated protein kinase (MAPK), NOD-like receptor protein 3, and Smads are important mechanisms of inflammatory kidney injury in DKD, and the NF-κB pathway plays a key role. The inflammatory factor network formed after activation of the NF-κB pathway connects different signaling pathways and exacerbates renal inflammatory damage. Many traditional Chinese medicine compounds, single agents, effective components and active ingredients can regulate the expression of key molecules in the signaling pathways associated with inflammatory injury, such as transforming growth factor-β activated kinase 1, NF-κB, p38MAPK, NOD-like receptor protein 3, and Smad7. These treatments have the characteristics of multiple targets and have multiple and overlapping effects, which can treat DKD kidney inflammation and injury through multiple mechanisms and apply the "holistic concept" of traditional Chinese medicine.