This study was conducted to elucidate the mechanism of action of the Traditional Chinese Medicine XinShuaiNing (XSN) formula in CHF based on network pharmacology. A total of 489 compounds in the XSN formula were screened. These compounds predicted 778 targets. A search of CHF yielded 789 corresponding targets, and 151 intersections between the potential targets of the XSN formula and CHF, involving AKT1, AGT, eNOS, and VEGF. Abdominal aortic coarctation (AAC) was used to establish a CHF rat model, and isoproterenol-induced H9c2 cells to establish a myocardial injury cell model. The results showed that the XSN formula downregulated ET-1, BNP, and Hcy and upregulated the ALB levels and also relieved cardiac histopathological damage. The XSN formula reduced the content of pro-inflammatory factors and inhibited the apoptosis of cardiomyocytes. In addition, the expression of fibronectin, α-SMA, collagen 1, and collagen 3 was downregulated by XSN formula treatment, and the fibrotic areas of myocardial tissue were reduced. The XSN formula promoted phosphorylation of AKT1-induced VEGF and eNOS signaling and inhibited AGT signaling. Besides, the XSN formula can affect the apoptosis of H9c2 cells by affecting AKT1, AGT, eNOS, and VEGF. The XSN formula regulates inflammatory factors by inducing phosphorylation of AKT1, upregulating eNOS and VEGF, and downregulating AGT to protect cardiomyocytes from apoptosis and myocardial fibrosis to alleviate CHF. In conclusion, this study identified the target of XSN prescription through network pharmacology screening and experimental validation and confirmed its anti-inflammatory, antiapoptotic, and antifibrotic effects.

Traditional drug discovery approach is based on one drug-one target, that is associated with very lengthy timelines, high costs and very low success rates. Network pharmacology (NP) is a novel method of drug designing, that is based on a multiple-target approach. NP integrates systems such as biology, pharmacology and computational techniques to address the limitations of traditional methods of drug discovery. With help of mapping biological networks, it provides deep insights into biological molecules' interactions and enhances our understanding to the mechanism of drugs, polypharmacology and disease etiology. This review explores the theoretical framework of network pharmacology, discussing the principles and methodologies that enable the construction of drug-target and disease-gene networks. It highlights how data mining, bioinformatics tools and computational models are utilised to predict drug behaviour, repurpose existing drugs and identify novel therapeutic targets. Applications of network pharmacology in the treatment of complex diseases-such as cancer, neurodegenerative disorders, cardiovascular diseases and infectious diseases-are extensively covered, demonstrating its potential to identify multi-target drugs for multifaceted disease mechanisms. Despite the promising results, NP faces challenges due to incomplete and quality of biological data, computational complexities and biological system redundancy. It also faces regulatory challenges in drug approval, demanding revision in regulatory guidelines towards multi-target therapies. Advancements in AI and machine learning, dynamic network modelling and global collaboration can further enhance the efficacy of network pharmacology. This integrative approach has the potential to revolutionise drug discovery, offering new solutions for personalised medicine, drug repurposing and tackling the complexities of modern diseases.

Andrographolide (AG), one of the main active components of Andrographis paniculata (Burm.f.) Wall. ex Nees, has been proved to possess the pharmacological function of anti-inflammation in multiple disease including asthma. But the potential mechanism is still not clear. In this study, network pharmacology, molecular docking and experimental validation were utilized to explore the molecular mechanism of AG in the treatment of asthma. AG-related targets and asthma-related targets were screened by Swiss Target Prediction, DrugBank, STITCH, OMIM, Genecards and TTD databases. A protein-protein interaction (PPI) network was obtained through the STRING Database. The plug-in of "Network Analyzer" in Cytoscape 3.7.1 software was used to conduct the topological analysis. GO enrichment and KEGG pathway analysis were achieved by Metascape database and Bioinformatics platform. The target-pathway network was acquired by Cytoscape 3.7.1 software. The binding affinity between AG and the target genes was evaluated by Molecular docking with AutoDockTools 1.5.6. Flow cytometry was also used to verify the mechanism behind the treatment of asthma by AG, which was predicted in network pharmacology. In total, 38 targets were identified as potential targets of AG against asthma. The top 10 targets revealed by PPI are: IL-6, IL-1B, NFKB1, MMP9, CDK2, CREBBP, MAP2K1, JAK1, AR, PRKCA. GO and KEGG analysis showed that AG treatment of asthma mainly involved protein phosphorylation, peptidyl-serine phosphorylation, peptidyl-amino acid modification and other biological processes. The main signaling pathways are Th17 cell differentiation, JAK-STAT signaling pathway and PI3K-Akt signaling pathway. Molecular docking showed that AG has higher affinity with MMP9, PRKCA, JAK2, LTGAL and LRRK2. Flow cytometry showed that Th17 cell differentiation may be the potential target of AG in the treatment of asthma. This study successfully revealed the underlying target genes and mechanism involved in the treatment of asthma for AG, providing a reference and guidance for future mechanism research.

The persistently high mortality rates associated with cancer underscore the imperative need for innovative, efficacious, and safer therapeutic agents, as well as a more nuanced understanding of tumor biology. Patient-derived organoids (PDOs) have emerged as innovative preclinical models with significant translational potential, capable of accurately recapitulating the structural, functional, and heterogeneous characteristics of primary tumors. When integrated with cutting-edge genomic tools such as CRISPR, PDOs provide a powerful platform for identifying cancer driver genes and novel therapeutic targets. This comprehensive review delves into recent advancements in CRISPR-mediated functional screens leveraging PDOs across diverse cancer types, highlighting their pivotal role in high-throughput functional genomics and tumor microenvironment (TME) modeling. Furthermore, this review highlights the synergistic potential of integrating PDOs with CRISPR screens in cancer immunotherapy, focusing on uncovering immune evasion mechanisms and improving the efficacy of immunotherapeutic approaches. Together, these cutting-edge technologies offer significant promise for advancing precision oncology.

Drug-induced liver injury (DILI) results from the liver toxicity caused by drugs or their metabolites. Gallic acid (GA) is a naturally occurring secondary metabolite found in many fruits, plants, and nuts. Recently, GA has drawn increasing attention due to its potent pharmacological properties, particularly its anti-inflammatory and antioxidant capabilities. To the best of our knowledge, this is the first review to focus on the pharmacological properties of GA and related molecular activation mechanisms regarding protection against hepatotoxicity. We also provide a thorough explanation of the physicochemical properties, fruit sources, toxicity, and pharmacokinetics of GA after reviewing a substantial number of studies. Pharmacokinetic studies have shown that GA is quickly absorbed and eliminated when taken orally, which restricts its use in development. However, the bioavailability of GA can be increased by optimizing its structure or changing its form of administration. Notably, according to toxicology studies conducted on a range of animals and clinical trials, GA rarely exhibits toxicity or side effects. The antioxidation mechanisms mainly involved Nrf2, while anti-inflammatory mechanisms involved MAPKs and NF-κB signaling pathways. Owing to its marked pharmacological properties, GA is a prospective candidate for the management of diverse xenobiotic-induced hepatotoxicity. We also discuss the applications of cutting-edge technologies (nano-delivery systems, network pharmacology, and liver organoids) in DILI. In addition to guiding future research and development of GA as a medicine, this study offers a theoretical foundation for its clinical application.

Rhodiola is a common Chinese herb in the treatment of cerebral small vessel disease (cSVD). Umbelliferone, one of the effective components of Rhodiola, can protect the endothelial barrier. But its mechanisms are still unclear. Therefore, this study is aimed to explore mechanisms of umbelliferone of an effective component of Rhodiola in protecting the cerebral microvascular endothelial barrier in cSVD.

Firstly, ETCM, SwissTargetPrediction and literatures were used to screen components and targets of Rhodiola. GeneCards was used to obtain targets of cSVD. STRING and Cytoscape were utilized for building the PPI and C-T network. Metascape was utilized to construct GO and KEGG enrichment analysis. Then, molecular docking was employed to evaluate the binding ability of the compounds for their respective target molecules. Ultimately, the endothelial cell damage caused by OGD was employed to explore the protective impact of umbelliferone, a bioactive constituent of Rhodiola, on the endothelial barrier. Endothelial cell leakage and migration assays were used to assess the permeability and migration ability of endothelial cells. IF and WB techniques were employed to ascertain the expression of endothelial tight junction protein. The major target proteins and related pathways were validated by WB.

Six effective components and 106 potential targets were identified and 1885 targets of cSVD were obtained. Nine key targets were selected. GO and KEGG enrichment analysis suggested that effects of Rhodiola in cSVD were associated with PI3K-Akt, Ras, Rap1 and MAPK signal pathways. Molecular docking results showed good binding ability between 28 pairs of key proteins and compounds. Umbelliferone of an effective component of Rhodiola can protect tight junction proteins and improve the permeability and migration ability of endothelial cells damaged by OGD through MMP9, MMP2, CCND1, PTGS2 and PI3K-Akt, Ras, Rap1 signaling pathways.

Our study systematically clarified mechanisms of Rhodiola in treating cSVD by network pharmacology and molecular docking, characterized by its multi-component, multi-target and multi-pathway effects. This finding was validated through in vitro tests, which demonstrated that umbelliferone of an effective component in Rhodiola can protect the brain microvascular endothelial barrier. It provided valuable ideas and references for additional research.

S. glabra has been widely used to treat tumors in traditional Chinese medicine (TCM). However, the specific mechanism of action of S. glabra in pancreatic cancer remains unclear. In this study, network pharmacological analysis was used to identify the active components of S. glabra and their corresponding targets for the treatment of pancreatic cancer. Furthermore, molecular docking, molecular dynamic simulations, and in vitro experiments were performed to validate the findings.

The active components of S. glabra and their corresponding targets for the treatment of pancreatic cancer were identified using the TCMSP database and a literature search. Differentially expressed genes were identified using data from the Gene Expression Omnibus (GEO) database, and their protein-protein interaction (PPI) network was constructed using the STRING platform. The target genes of S. glabra were further assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses in the R software. Subsequently, a protein-protein interaction (PPI) network and a composite target-pathway network were established. The target genes were subjected to survival and mutation analyses. Molecular docking and molecular dynamic simulations were used to validate the interaction between the hub target genes and S. glabra in vitro. In addition, cell viability and qRT-PCR verification of S. glabra against pancreatic cancer in vitro.

A total of 20 active components and 70 targets were identified. Based on the PPI network, CASP3, MMP9, CCND1, EGF, MMP2, CASP8, ERBB2, STAT1, and PPARG were identified as hub target genes. Enrichment analysis showed that S. glabra may primarily affect pathways such as p53 signaling, transcriptional dysregulation in cancer, proteoglycans in cancer, pancreatic cancer, and cell cycle. Molecular docking and molecular dynamic simulations indicated stable binding between anhydroicaritin-GSK3B and quercetin-PPARG. In vitro experiments demonstrated that treatment with S. glabra significantly inhibited the growth of PANC-1 cells and downregulated expression of GSK3B and PPARG (P < 0.05).

This study demonstrates the potential of S. glabra, a herb in traditional Chinese medicine, for treating pancreatic cancer. The findings provide insights into the mechanism of action of the active ingredients of S. glabra, offering a strong theoretical foundation for its various clinical applications.

Not applicable.

Chenpi (the dried mature peel of Citrus reticulata Blanco) and Rougui (the dried bark of Cinnamomum cassia Presl) are both edible and medicinal plants, which have therapeutic effects on nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms necessitate further exploration. This study evaluated the prevention effect of Chenpi-Rougui herb pair (CRP) on NAFLD using an integrated strategy that combined network pharmacology with metabolomics.

Initially, the components in CRP decoction were characterized by UPLC-QTOF-MS/MS. Subsequently, a high-fat diet induced NAFLD mouse model was used to assess the efficacy of CRP and its individual constituent, Chenpi and Rougui. Additionally, synergetic pathways and crucial targets for CRP therapy in NAFLD were identified using network pharmacology and serum metabolomics. Finally, real-time polymerase chain reaction (RT-PCR) was utilized to validate relevant genes.

CRP exerted a more extensive prevention effect on NAFLD mice compared to the individual herb of Chenpi and Rougui. A total of 105 compounds were characterized from CRP, which were linked to 70 potential therapeutic targets for NAFLD. Thirty-two differential metabolites were identified by metabolomics, which were co-regulated by Chenpi, Rougui and CRP. Pathways associated with the intervention of herb pair in NAFLD included energy metabolism, fatty acid metabolism, glycerophospholipid metabolism, sphingolipids metabolism, arachidonic acid metabolism, sterol and bile acid metabolism. Finally, eight targets were screened through conjoint analysis and experimental verification showed that six of them including FASN, AKT1, CASP3, F2, PTGS2 and PRKCA, could be modulated by CRP in NAFLD mice. Besides, Chenpi primarily regulated FASN, AKT1, CASP3 and PRKCA, which were associated with reducing apoptosis in hepatocytes, while Rougui exceled in regulating F2 and PTGS2, closely linked to its anti-inflammatory properties. The combination of Chenpi and Rougui resulted in a broader influence on metabolites, pathways, and primary targets compared to their individual application.

These results provided valuable insights into the compatibility mechanism of CRP for treating NAFLD, and could also improve the value of its forthcoming application and development as a natural liver protective agent.

"Jiedu Tongluo Tiaoying Formula" (JDTLTYF) is a kind of traditional Chinese medicine (TCM) prescription for treating hyperthyroidism, which can effectively improve the condition of patients. The main active ingredients of JDTLTYF were collected from the traditional Chinese medicine systems pharmacology (TCMSP) database, and the target was predicted. Genes related to hyperthyroidism were identified using DisGeNET, GeneCards, and Online Mendelian Inheritance in Man (OMIM) databases. Protein-protein interaction (PPI) network and interaction network of "formula-herb-active ingredient-target genes" was constructed. Mass spectrometry was used to identify the components. The binding of key components to the target was verified by molecular docking and molecular dynamics (MD) simulations. A hyperthyroidism mouse model was established by using levothyroxine sodium tablets, and the hormone and expression levels of inflammatory factors were examined by ELISA and Western blot. The key genes of JDTLTYF in the treatment of hyperthyroidism were TNF and AKT1. The results of mass spectrometry also showed that quercetin was one of the main components. The results of molecular docking and MD simulation showed that the binding-free energy between AKT1 and quercetin was the lowest, and the binding was stable. In vivo experimental results showed that gastric lavage with JDTLTYF could target AKT1 and TNF-α, effectively alleviate the pathological features of hyperthyroidism in mice, and reduce inflammation response. This study elucidated the key small molecule compounds and their action targets of JDTLTYF in the treatment of hyperthyroidism. It provides a direction for the development of new drugs for clinical hyperthyroidism.NEW & NOTEWORTHY Based on the network pharmacology and molecular dynamics (MD) simulation, this study elucidated the key small molecule compounds and their action targets of JDTLTYF Chinese herbal prescription (debark peony root, common selfheal fruit-spike, figwort root, thunberg fritillary bulb, and oyster shell) in the treatment of hyperthyroidism, preliminarily analyzed its molecular mechanism, and provided a reference direction for subsequent cell experiments.

The herbal formula Sinisan (SNS) is a commonly used treatment for depression; however, its mechanism of action remains unclear. This article uses a combination of the GEO database, network pharmacology and molecular docking technologies to investigate the mechanism of action of SNS. The aim is to provide new insights and methods for future depression treatments. The study aims to extract effective compounds and targets for the treatment of depression from the T CMSP database. Relevant targets were searched using the GEO, Disgenet, Drugbank, PharmGKB and T T D databases, followed by screening of core targets. In addition, GO and KEGG pathway enrichment analyses were performed to explore potential pathways for the treatment of depression. Molecular docking was used to evaluate the potential targets and compounds and to identify the optimal core protein-compound complex. Molecular dynamics was used to further investigate the dynamic variability and stability of the complex. The study identified 118 active SNS components and 208 corresponding targets. Topological analysis of P P I networks identified 11 core targets. GO and KEGG pathway enrichment analyses revealed that the mechanism of action for depression involves genes associated with inflammation, apoptosis, oxidative stress, and the MAP K3 and P I3K-Akt signalling pathways. Molecular docking and dynamics simulations showed a strong binding affinity between these compounds and the screened targets, indicating promising biological activity. The present study investigated the active components, targets and pathways of SNS in the treatment of depression. Through a preliminary investigation, key signalling pathways and compounds were identified. These findings provide new directions and ideas for future research on the therapeutic mechanism of SNS and its clinical application in the treatment of depression.

Efficient virtual screening methods can expedite drug discovery and facilitate the development of innovative therapeutics. This study presents a novel transfer learning model based on network target theory, integrating deep learning techniques with diverse biological molecular networks to predict drug-disease interactions. By incorporating network techniques that leverage vast existing knowledge, the approach enables the extraction of more precise and informative drug features, resulting in the identification of 88,161 drug-disease interactions involving 7,940 drugs and 2,986 diseases. Furthermore, this model effectively addresses the challenge of balancing large-scale positive and negative samples, leading to improved performance across various evaluation metrics such as an Area under curve (AUC) of 0.9298 and an F1 score of 0.6316. Moreover, the algorithm accurately predicts drug combinations and achieves an F1 score of 0.7746 after fine-tuning. Additionally, it identifies two previously unexplored synergistic drug combinations for distinct cancer types in disease-specific biological network environments. These findings are further validated through in vitro cytotoxicity assays, demonstrating the potential of the model to enhance drug development and identify effective treatment regimens for specific diseases.

Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder characterized by the absence of organic lesions; it affects nearly one-fifth of the global population. There is currently no specific drug for treating it. Citri reticulatae Pericarpium (CRP) has been utilized in China for millennia as a therapeutic agent for alleviating bloating and spleen-stomach disharmony. Nonetheless, the curative efficacy and precise molecular mechanisms implicated in FD warrant further investigation. This study aims to address this gap by investigating the potential mechanisms of CRP against FD using HPLC-ESI-QTOF-MS, network analysis prediction, and experimental validation. In this study, 90 CRP metabolites were identified by HPLC-ESI-QTOF-MS; 70 common targets of CRP and FD were extracted, and the top ten overlapped targets included MAPK1, MAPK2, and MAPK3. KEGG enrichment analysis revealed that the MAPK pathways were predominant and involved the TLR4 signaling pathway. In vivo experiments demonstrated that after 14 days of treatment, CRP improved body weight, gastric emptying rate, intestinal transit rate, and the pathological structure of the gastric tissue. Serum IL-6, TNF-α, and IL-1β were downregulated, and the expressions of TLR4, MyD88, p-NF-κB, and MAPKs were suppressed in gastric tissue. Furthermore, CRP increased the relative abundance of Patescibateria and Bacteroidota, accompanied by a reduction in the relative abundance of Verrucomicrobota and Proteobacteria. In brief, CRP could attenuate dyspepsia by reducing the activation of inflammation-related TLR4/MyD88 and MAPK signaling pathways and by mediating gut microbial structure and composition. This study provides a unique perspective for further research on drugs for treating FD.

Lumbar disc herniation (LDH) significantly impacts individuals, particularly those aged 40-45. Traditional Chinese Medicine (TCM) formulations such as Taohong Siwu Decoction (TSD), Yaotong Jizheng Decoction (YJD), and Panlong Qi Tablet (PQT) are widely used for treatment. This study introduces dose-weighted network pharmacology, a novel approach that incorporates drug dosage as a quantitative factor into network analysis to evaluate better and compare the therapeutic potential of TCM formulations.

This study combines drug dosage with the PPI network to propose a theoretical algorithm for comparing the therapeutic efficacy of different traditional Chinese medicine formulations. The VIKOR method was used to assess the importance of therapeutic targets, with weights assigned based on both drug and disease perspectives. TSD, YJD, and PQT were evaluated in animal experiments, and the algorithm's feasibility was validated through GO and KEGG pathway analysis, Thermal Hyperalgesia Test, H&E staining, Western blotting (WB), RT-PCR, and ELISA assays.

The computational model indicated that YJD and PQT had higher predicted efficacy compared to TSD. These predictions were confirmed in animal studies, where YJD demonstrated the greatest reduction in thermal hyperalgesia and the most significant decrease in inflammatory markers, surpassing both TSD and PQT. GO and KEGG pathway analyses highlighted key pathways related to oxidative stress and inflammation, providing mechanistic insights into the effectiveness of the treatments.

Incorporating dosage as a reference factor into network pharmacology research proved feasible and effective, emphasizing the importance of precise dosage control in TCM formulations for treating LDH. The new algorithm provided reliable predictions, demonstrating its potential to enhance the design and evaluation of TCM formulations. Future improvements, such as establishing a target acceptance rate database, could further refine the algorithm, expanding its application in personalized medicine and targeted therapy.

To deeply explore the mechanism of pachymic acid (PA) intervention in myocardial ischemia, providing new ideas and methods for the treatment of myocardial ischemia.

Predict the targets of PA for improving myocardial ischemia, and conduct functional enrichment analysis using databases, such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome. To verify these findings, PPI network topology analysis and molecular docking were used to screen key targets and main mechanisms of action and further validated through in vitro experiments on the H9C2 cell line.

PA can significantly alleviate myocardial damage caused by hypoxia/reoxygenation, effectively reversing the abnormalities of oxidative stress indicators such as LDH, MDA, SOD, and ROS. PA may exert its effects through 39 targets, particularly by regulating the downregulation of autophagy-related proteins LC3-II and Beclin-1 expression via MTOR, thereby inhibiting excessive autophagy in cardiomyocytes.

PA protects myocardial cells during myocardial ischemia through various pathways, particularly by regulating mTOR to inhibit excessive autophagy.

Luteolin, a flavonoid found in various medicinal plants, has shown promising antioxidant, anti-inflammatory, and anti-aging properties. The cartilaginous endplate (CEP) represents a crucial constituent of the intervertebral disc (IVD), assuming a pivotal responsibility in upholding both the structural and functional stability of the IVD.

Exploring the precise mechanism underlying the protective effects of luteolin against senescence and degeneration of endplate chondrocytes (EPCs).

Relevant targets associated with luteolin and aging were obtained from publicly available databases. To ascertain cellular functions and signaling pathways, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed. Core genes were identified through the construction of a protein-protein interaction (PPI) network. Molecular docking (MD) was utilized to assess the binding affinity of luteolin to these core genes. Finally, the impact of luteolin on the senescence and degeneration of EPCs was evaluated in an in vitro cellular senescence model induced by tert-butyl hydroperoxide (TBHP).

There are 145 overlapping targets between luteolin and senescence. Analysis using GO revealed that these targets primarily participate in cellular response to oxidative stress and reactive oxygen species. KEGG analysis demonstrated that these markers mainly associate with signaling pathways such as p53 and PI3K-Akt. MD simulations exhibited luteolin's binding affinity to P53, Cyclin-dependent kinase (CDK)2, and CDK4. Cell cycle, cell proliferation, and β- galactosidase assays confirmed that luteolin mitigated senescence in SW1353 cells. Western blot assays exhibited that luteolin significantly suppressed the expression of Matrix Metallopeptidase (MMP) 13, P53, and P21, while concurrently promoting CDK2, CDK4, and Collagen Type II Alpha 1 (COL2A1) expression.

In summary, luteolin demonstrated beneficial properties against aging and degeneration in EPCs, offering novel insights to mitigate the progression of intervertebral disc degeneration (IVDD).

Sanguinarine (SAN) has been reported to have antioxidant, antiinflammatory, and antimicrobial activities with potential for the treatment of osteoporosis (OP).

This work purposed to unravel the molecular mechanisms of SAN in the treatment of OP.

OP-related genes and SAN-related targets were predicted from public databases. Differential expression analysis and VennDiagram were adopted to detect SAN-related targets against OP. Protein-protein interaction (PPI) network was served for core target identification. Molecular docking and DeepPurpose algorithm were further adopted to investigate the binding ability between core targets and SAN. Gene pathway scoring of these targets was calculated utilizing gene set variation analysis (GSVA). Finally, we explored the effect of SAN on the expressions of core targets in preosteoblastic MC3T3-E1 cells.

A total of 21 candidate targets of SAN against OP were acquired. Furthermore, six core targets were identified, among which CASP3, CTNNB1, and ERBB2 were remarkably differentially expressed in OP and healthy individuals. The binding energies of SAN with CASP3, CTNNB1, and ERBB2 were -6, -6.731, and -7.162 kcal/mol, respectively. Moreover, the GSVA scores of the Wnt/calcium signaling pathway were significantly lower in OP cases than in healthy individuals. In addition, the expression of CASP3 was positively associated with Wnt/calcium signaling pathway. CASP3 and ERBB2 were significantly lower expressed in SAN group than in DMSO group, whereas the expression of CTNNB1 was in contrast.

CASP3, CTNNB1, and ERBB2 emerge as potential targets of SAN in OP prevention and treatment.

Ischemic stroke is a prevalent and life-threatening cerebrovascular disease that is challenging to treat and associated with a poor prognosis. Astragaloside IV (AS-IV), a primary bioactive component of Astragali radix, has demonstrated neuroprotective benefits in previous studies. This study aimed to explore the mechanisms through which AS-IV may treat cerebral ischemia-reperfusion injury (CIRI).

Network pharmacology was employed to identify key targets and pathways of AS-IV in CIRI therapy, combined with molecular docking to predict binding affinity. Male Sprague-Dawley rats were randomly assigned to sham, MCAO/R, AS-IV, SP600125 (JNK inhibitor), AS-IV + SP600125, and 3-n-Butylphthalide (NBP) groups. Neurobehavioral deficits were assessed, and brain tissue damage was visualized through 2,3,5-triphenyltetrazolium chloride, H&E, and TUNEL staining. Immunohistochemistry was employed to detect CytC- and caspase-3-positive cells, while Western blotting, qPCR, and ELISAs were used to analyze apoptosis-related markers.

A total of 48 key targets of AS-IV predicted to be involved in the treatment of CIRI were identified, enriched in 136 pathways. AS-IV was effectively bound to the top five targets from 48 targets, and those associated with the c-Jun N-terminal kinase (JNK)/Bid pathway, with binding energy values below -5.0 kJ·mol-1. JNK inhibition reduced infarcted brain areas, improved neurological function, reduced pathological brain tissue damage, and inhibited apoptosis, with AS-IV achieving similar neuroprotective effects. Both AS-IV and SP600125 reduced p-JNK, Bid, CytC, Apaf-1, caspase-3, and cleaved caspase-3 levels in rats while decreasing CytC, caspase-3, and caspase-9 levels in serum.

AS-IV may suppress apoptosis partly through the modulation of JNK/Bid signaling, exerting neuroprotective effects. These findings support the potential development of AS-IV-based therapies for stroke treatment.

Many neurological diseases can lead to cognitive impairment in patients, which includes dementia and mild cognitive impairment and thus create a heavy burden both to their families and public health. Due to the limited effectiveness of medications in treating cognitive impairment, it is imperative to develop alternative treatments. Electroacupuncture (EA), a required method for Traditional Chinese Medicine, has the potential treatment of cognitive impairment. However, the molecular mechanisms involved have not been fully elucidated. Considering the current research status, preclinical literature published within the ten years until October 2022 was systematically searched through PubMed, Web of Science, MEDLINE, Ovid, and Embase. By reading the titles and abstracts, a total of 56 studies were initially included. It is concluded that EA can effectively ameliorate cognitive impairment in preclinical research of neurological diseases and induce potentially beneficial changes in molecular pathways, including Alzheimer's disease, vascular cognitive impairment, chronic pain, and Parkinson's disease. Moreover, EA exerts beneficial effects through the same or diverse mechanisms for different disease types, including but not limited to neuroinflammation, neuronal apoptosis, neurogenesis, synaptic plasticity, and autophagy. However, these findings raise further questions that need to be elucidated. Overall, EA therapy for cognitive impairment is an area with great promise, even though more research regarding its detailed mechanisms is warranted.

Premature Ovarian Insufficiency (POI) is a disease suffered by women under the age of 40 when ovarian function has declined, seriously affecting both the physical and mental health of women. Guiluoshi Anzang decoction (GLSAZD) has been used for a long time and has a unique therapeutic effect on improving ovarian function. This study aims to investigate the mechanism of GLSAZD in treating POI through network pharmacology, molecular docking, and experimental verification.

In this study, the active ingredients of Guiluoshi Anzang Decoction and the targets of POI were obtained from TCMSP, BATMANN-TCM, Uniprot, GeneCards, and other databases, and network pharmacology analysis was performed. Molecular docking was conducted to validate the affinity of the main active ingredient of GLSAZD to key POI targets. A POI SD rat model was established, and HE staining, ELISA, Real-time PCR, and Western blot experiments were performed to verify the predicted core targets and the therapeutic effects.

10 core targets and the top 5 ingredients were screened out. Molecular docking showed core targets AKT1, CASP3, TNF, TP53, and IL6 had stable binding with the core 5 ingredients quercetin, kaempferol, beta-sitosterol, luteolin, and Stigmasterol. GO and KEGG enrichment analysis demonstrated the mechanism involved in the positive regulation of gene expression, PI3K-AKT signaling pathway, and apoptosis signaling pathways. Animal experiments indicated GLSAZD could up-regulate the protein expression of p-PI3K and p-AKT1 and the mRNA expression of STAT3 and VEGF, down-regulate TP53 and Cleaved Caspase-3 protein expression in rat`s ovarian tissues and serum TNF-α and IL-6 protein levels, activate PI3K-AKT signaling pathway and inhibit the apoptosis signaling pathway.

GLSAZD treats POI through multi-component, multi-target, and multi-pathway approaches. This study provided evidence for its clinical application in treating POI and shed light on the study of traditional medicine of the Guangxi Zhuang Autonomous Region in China.

Chronic hepatitis (CH) refers to liver inflammation lasting at least 6 months caused by various factors, significantly impacting patients' daily lives. Paeoniae Radix Rubra (CS) is a classic blood-activating and stasis-dissolving herb known for its protective effects on the liver. This research seeks to investigate the underlying mechanisms by which CS treat CH, employing network pharmacology and molecular docking.

The active constituents of CS for CH treatment were identified through the TCMSP database. Targets associated with CH were gathered from GeneCards, the Therapeutic Target Database, and OMIM databases. The intersecting genes between these targets and the components of CS were considered potential therapeutic targets. Protein-protein interaction analysis was performed with the use of the STRING database and Cytoscape software, leading to the identification of core targets. These core targets underwent KEGG and GO enrichment analysis, and the top 10 pathways were chosen for building a drug-compound-target-pathway-disease' network. Finally, molecular docking was utilized to evaluate the binding affinities between the compounds and the core targets.

From the TCMSP database, 29 compounds were screened, and 101 potential intersection targets of CS for treating CH were identified. The protein-protein interaction network analysis revealed that the core targets included EGFR, HSP90AA1, SRC, TNF, ALB, ESR1, CASP3, PTGS2, ERBB2, and FGF2. Pathway analysis indicated that CS's treatment of CH is mainly associated with the pathway in cancer. Molecular docking results indicated that Paeoniflorin and Baicalin exhibited strong binding affinity with EGFR and HSP90AA1.

This research uncovers the possible mechanisms of CS in CH treatment, offering new avenues for future studies.

The mechanisms of Traditional Chinese Medicine (TCM) Guizhi-Gancao Decoction (GGD) remain unknown.

This study explores the mechanisms of GGD against cardiac hypertrophy.

Network pharmacology analysis was carried out to identify the potential targets of GGD. In vivo experiments, C57BL/6J mice were divided into Con, phenylephrine (PE, 10 mg/kg/d), 2-chloroadenosine (CADO, the stable analogue of adenosine, 2 mg/kg/d), GGD (5.4 g/kg/d) and GGD (5.4 g/kg/d) + CGS15943 (a nonselective adenosine receptor antagonist, 4 mg/kg/d). In vitro experiments, primary neonatal rat cardiomyocytes (NRCM) were divided into Con, PE (100 µM), CADO (5 µM), GGD (10-5 g/mL) and GGD (10-5 g/mL) + CGS15943 (5 µM). Ultrasound, H&E and Masson staining, hypertrophic genes expression and cell surface area were conducted to verify the GGD efficacy. Adenosine receptors (ADORs) expression were tested via real-time polymerase chain reaction (PCR), western blotting and immunofluorescence analysis.

Network pharmacology identified ADORs among those of the core targets of GGD. In vitro experiments demonstrated that GGD attenuated PE-induced increased surface area (with an EC50 of 5.484 × 10-6 g/mL). In vivo data shown that GGD attenuated PE-induced ventricular wall thickening. In vitro and in vivo data indicated that GGD alleviated PE-induced hypertrophic gene expression (e.g., ANP, BNP and MYH7/MYH6), A1AR over-expression and A2aAR down-expression. Moreover, CADO exerts effects similar to GGD, whereas CGS15943 eliminated most effects of GGD.

Our findings suggest the mechanism by which GGD inhibits cardiac hypertrophy, highlighting regulation of ADORs as a potential therapeutic strategy for HF.

To investigate the target and mechanism of action of Bushen Huoxue Recipe (BSHX) for the treatment of infertility in polycystic ovary syndrome (PCOS), to provide a basis for the development and clinical application of herbal compounds.

Prediction and validation of active ingredients and targets of BSHX for the treatment of PCOS by using network pharmacology-molecular docking technology. In an animal experiment, the rats were randomly divided into four groups (control group, model group, BSHX group, metformin group, n = 16 in each group), and letrozole combined with high-fat emulsion gavage was used to establish a PCOS rat model. Body weight, vaginal smears, and number of embryos were recorded for each group of rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of ovarian and endometrial tissues, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the serum inflammatory factor levels. Expression levels of transforming growth factor-β (TGF-β), transforming growth factor beta activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), Vimentin, and E-cadherin proteins were measured by western blot (WB).

Ninety active pharmaceutical ingredients were obtained from BSHX, involving 201 protein targets, of which 160 were potential therapeutic targets. The active ingredients of BSHX exhibited lower binding energy with tumor necrosis factor-α (TNF-α), TGF-β, TAK1, and NF-κB protein receptors (< -5.0 kcal/mol). BSHX significantly reduced serum TNF-α levels in PCOS rats (p < .01), effectively regulated the estrous cycle, restored the pathological changes in the ovary and endometrium, improved the pregnancy rate, and increased the number of embryos. The results of WB suggested that BSHX can down-regulate protein expression levels of TGF-β and NF-κB in endometrial tissue (p < .05), promote the expression level of E-cadherin protein (p < .001), intervene in the endometrial epithelial-mesenchymal transition (EMT) process.

TGF-β, TAK1, NF-κB, and TNF-α are important targets of BSHX for treating infertility in PCOS. BSHX improves the inflammatory state of PCOS, intervenes in the endometrial EMT process through the TGF-β/NF-κB pathway, and restores endometrial pathological changes, further improving the pregnancy outcome in PCOS.

Goutengsan (GTS) is a traditional Chinese medicine formula that can improve multiple nervous system diseases, such as methamphetamine (MA) dependence. However, the mechanism how GTS treats MA dependence remains unclear. This study was aimed to investigate the action mechanism of GTS on MA dependence using network pharmacology, in vivo/in vitro experimental validation, pharmacokinetics, and tissue distribution in the brain.

The bioactive ingredients from GTS and possible targeted genes for treating MA dependence were predicted using network pharmacology. The binding of key components of GTS to the predicted proteins was studied using molecular docking, and the key components were verified by HPLC. The effects of GTS on an MA-induced model in rats and SH-SY5Y cells were studied. The regulatory effects of GTS on the expressions of predicted MAPK pathway-related proteins in rat brain tissues and SH-SY5Y cells were validated. Furthermore, the plasma exposure and brain tissue distribution of GTS ingredients for MA dependence treatment and MAPK pathway regulation were studied in mice.

Network pharmacology screened 53 active ingredients, and 287 potential targets of GTS, and showed the MAPK pathway was among the most relevant pathways. Molecular docking showed that key active ingredients (e.g., 6-gingerol, liquiritin and rhynchophylline) bound strongly with MAPK core targets, such as MAPK3, and MAPK8. Five compounds of GTS were detected by HPLC, including 6-gingerol, chlorogenic acid, liquiritin, 5-o-methylviscumaboloside and hesperidin. GTS had a therapeutic effect on MA-dependent rats, and reduced hippocampal CA1 damage and relative expressions of p-MAPK3/MAPK3, p-MAPK8/MAPK8 in brain tissues induced by MA. GTS counteracted aberrant alterations in cAMP, 5-TH and cellular morphology induced by MA induction and exerts therapeutic effects on MA-induced SH-SY5Y cell models. GTS also can antagonize the high expressions of MAPK-related proteins in MA-induced SH-SY5Y cells. Pharmacokinetic experiment revealed the four ingredients of GTS (e.g., chlorogenic acid, 5-o-methylviscumaboloside, hesperidin and rhynchophylline) were exposed in the plasma and brain, which demonstrates its pharmacological effect on MA dependence.

GTS treats MA dependence by regulating the MAPK pathway via multiple bioactive ingredients. The network pharmacology, experimental validation and pharmacokinetics integrated strategy is efficient in discovering the key pharmacological mechanism of herbal formulae.

The biological targets of traditional Chinese medicine (TCM) are the core effectors mediating the interaction between TCM and the human body. Identification of TCM targets is essential to elucidate the chemical basis and mechanisms of TCM for treating diseases. Given the chemical complexity of TCM, both in silico high-throughput compound-target interaction predicting models and biological profile-based methods have been commonly applied for identifying TCM targets based on the structural information of TCM chemical components and biological information, respectively. However, the existing methods lack the integration of TCM chemical and biological information, resulting in difficulty in the systematic discovery of TCM action pathways. To solve this problem, we propose a novel target identification model NP-TCMtarget to explore the TCM target path by combining the overall chemical and biological profiles. First, NP-TCMtarget infers TCM effect targets by calculating associations between herb/disease inducible gene expression profiles and specific gene signatures for 8233 targets. Then, NP-TCMtarget utilizes a constructed binary classification model to predict binding targets of herbal ingredients. Finally, we can distinguish TCM direct and indirect targets by comparing the effect targets and binding targets to establish the action pathways of herbal component-direct target-indirect target by mapping TCM targets in the biological molecular network. We apply NP-TCMtarget to the formula XiaoKeAn to demonstrate the power of revealing the action pathways of herbal formula. We expect that this novel model could provide a systematic framework for exploring the molecular mechanisms of TCM at the target level. NP-TCMtarget is available at http://www.bcxnfz.top/NP-TCMtarget.

Ototoxicity is a common side effect of cisplatin cancer treatment, potentially leading to hearing loss. This study demonstrated the significant protective activity of Acanthopanax sessiliflorus (A. sessiliflorus) leaves against cisplatin-induced ototoxicity (CIO), investigated the active compounds, and elucidated their mechanisms in countering CIO. UPLC-Q/TOF-MS analysis identified 79 compounds. Network pharmacology and activity screening determined that chiisanoside (CSS) plays a crucial role in combating CIO. Transcriptomics combined with network pharmacology analysis and experiments revealed that CSS activates the Dock1/PIP5K1A pathway to suppress the actin-severing protein gelsolin, protecting hair cells from cisplatin-induced cytoskeleton damage. CSS also activates the SLC7A11/GPX4 pathway via TGFBR2, reducing lipid peroxidation and intracellular iron accumulation to suppress cisplatin-induced ferroptosis. This study discovers that the major component CSS in A. sessiliflorus leaves reverses CIO by regulating actin homeostasis via Dock1 and inhibiting ferroptosis through TGFBR2, providing a theoretical basis for expanding CIO treatment targets and related drug development.

Hepatocellular Carcinoma (HCC) is commonly treated with surgery, liver transplantation, and chemotherapy, but recurrence and metastasis remain challenges. Natural complementary therapies like propolis, known for its hepatoprotective properties, are gaining interest due to limited efficacy and toxicity of conventional chemotherapy. This study aims to identify core targets for HCC, assess the therapeutic potential of East Kalimantan propolis (EKP) from stingless bees, and analyze the molecular interactions.

EKP compounds were analyzed using target prediction tools related to HCC, alongside clinical data from the Gene Expression Omnibus (GEO) database, to identify overlapping genes with clinical relevance. The selected genes were then subjected to protein-protein interaction (PPI), GO and KEGG enrichment, immunohistochemical comparison and survival analysis to identify potential core targets and related pathways for HCC therapy. Furthermore, molecular docking and dynamics were conducted to verify the molecular interactions and stability of EKP compounds with targets.

108 genes have been selected as HCC potential targets, which mostly associated with MicroRNAs in cancer, chemical carcinogenesis, and viral carcinogenesis pathways. These targets were obtained by overlapping genes from GEO clinical databases and target predictors. PPI network analysis revealed 4 main targets of propolis in HCC. Furthermore, differential expression genes, survival analysis, and Immunohistochemical analysis from databases suggested that AKR1C3 and MAPK1 promote HCC progression and shorten survival rate of HCC patients. Molecular docking and dynamic studies confirmed strong binding affinity and stability of Baicalein, Chrysin, Quercetin, and Myricetin with receptor targets within simulation time.

This study provides insight into the mechanism of action of EKP on HCC and identifies AKR1C3 and MAPK1 as candidate target treatments for future drug development.

This study focused on examining the protection of QiShenYiQi dripping pills (QSYQ) against myocardial infarction (MI) and investigating its potential mechanisms. Ultra high performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was employed to analyze potential active compounds of QSYQ. The targets of these compounds were predicted using an integrated in silico method and cross-referenced with relevant databases to identify associated pathways. Experimental validation was then conducted to confirm the accuracy of the systems pharmacology findings. In the end, network analysis combined with UHPLC screened 13 potential active compounds and obtained 99 targets for the intersection of potential active compounds and diseases. The enrichment analysis results indicated that the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway might be the mechanism of action of QSYQ in the treatment of MI. Experimental verification demonstrated that QSYQ could alleviate oxidative stress, promote vasodilation, and activate proteins related to the mitochondrial ATP-sensitive potassium channel (KATP) and nitric oxide (NO)-cGMP-PKG signaling pathway. This study provides insights into both the pathogenic mechanisms underlying MI and the molecular mechanisms through which QSYQ may confer protection. Given the role of PKG in regulating myocardial stiffness, it emerges as a promising therapeutic target for myocardial remodeling. We propose that the NO-cGMP-PKG and mitochondrial KATP pathways may serve as candidate therapeutic targets for the development of new interventions for MI.

In biomedical research, the fruit fly (Drosophila melanogaster) is among the most effective and flexible model organisms. Through the use of the Drosophila model, molecular mechanisms of human diseases can be investigated and candidate pharmaceuticals can be screened. White rot fungus Inonotus obliquus is a member of the family Hymenochaetaceae. Due to its multifaceted pharmacological effects, this fungus has been the subject of scientific investigation. Nevertheless, the precise mechanisms by which Inonotus obliquus treats diseases remain unclear. In this study, we prepared an aqueous extract derived from Inonotus obliquus and demonstrated that it effectively prevented the negative impacts of inflammatory agents on flies, including overproliferation and overdifferentiation of intestinal progenitor cells and decreased survival rate. Furthermore, elevated reactive oxygen species levels and cell death were alleviated by Inonotus obliquus aqueous extract, suggesting that this extract inhibited intestinal inflammation. Additionally, Inonotus obliquus aqueous extract had an impact on the insulin pathway, as it alleviated growth defects in flies that were fed a high-sugar diet and in chico mutants. In addition, we determined the composition of Inonotus obliquus aqueous extract and conducted a network pharmacology analysis in order to identify prospective key compounds and targets. In brief, Inonotus obliquus aqueous extract exhibited considerable potential as a therapeutic intervention for human diseases. Our research has established a foundational framework that supports the potential clinical implementation of Inonotus obliquus.

This study explores the mechanism of AAC in intervening heart failure (HF) using network pharmacology, molecular docking, and in vitro experimental validation.

The "active component-target" network and the "drug-disease target" protein interaction network were constructed using Cytoscape 3.9.0 and STRING Database. GO and KEGG enrichment analysis was performed using DAVID database. Then, the molecular docking of major compounds and target proteins was carried out using Autodock 1.5.7, and visualized with PyMOL 2.4.0 software. Finally, in vitro experimental validation was performed to explore the potential targets of AAC in treating HF.

The study revealed significant targets implicated in a variety of GO bioprocess programs and KEGG signaling networks. The primary chemicals to have strong binding ability with target proteins in molecular docking, with quercetin having the best binding energy with MAPK at -6.72 Kcal/Mol.Validation of cellular experiments showed that AAC might reduce the apoptosis that doxorubicin causes in AC16 cells by controlling the levels of PIK3CA, AKT1, and MAPK1.

This study preliminarily reveals that AAC can treat HF through multiple components and multiple targets by using network pharmacology, molecular docking, and experimental validation.

We used evidence-based medicine, bioinformatics and experimental verification to comprehensively analyze the efficacy and pharmacological mechanism of Xuefu Zhuyu decoction (XFZYD) in the treatment of idiopathic pulmonary fibrosis (IPF).

Major databases were retrieved for randomized controlled trials (RCTs) of XFZYD treating IPF to perform meta-analysis. Active ingredients and target genes of XFZYD were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). IPF-related differentially expressed genes (DEGs) were identified from the Gene Expression Omnibus (GEO) database. The RGUI software was utilized for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The ingredient-target and protein-protein interaction (PPI) networks were achieved through Cytoscape software and the STRING database to identify the key compounds and target proteins. Molecular docking was performed using AutoDockTool and AutoDock Vina software. The effect between key compounds and target proteins was verified in animal experiments.

Six RCTs were included for meta-analysis, which uncovered that the total effective rate of clinical efficacy was higher in the experimental group than control group. Then, 156 active ingredients and 254 target genes of XFZYD, and 1,566 IPF-related DEGs were identified. The intersection analysis identified 48 target genes correlating with 130 active ingredients of XFZYD treating IPF. GO functional enrichment, KEGG pathway enrichment, ingredient-target network and PPI network were achieved. Following the identification of key compounds and target proteins, we performed molecular docking. Ultimately, our research focused on the key compound quercetin for experimental validation to assess its interactions with two key target proteins, JUN and PTGS2.

The effectiveness of XFZYD on IPF has been substantiated through evidence-based medicine. The pharmacological mechanism of XFZYD for IPF treatment involves a complex interplay of various compounds and targets, with quercetin exerting pronounced impacts on JUN and PTGS2 proteins.

Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs.

Abdominal aortic aneurysms (AAA) is a life-threatening disease and the incidence of AAA is still on the rise in recent years. Numerous studies suggest that dietary moderate consumption of polyphenol exerts beneficial effects on cardiovascular disease. Apigenin (API) is a promising dietary polyphenol and possesses potent beneficial effects on our body. Although our previous study revealed protective effects of API on experimental AAA formation, up till now few studies were carried out to further investigate its involved molecular mechanisms. In the present study, network pharmacology combined molecular docking and experimental validation was used to explore API-related therapeutic targets and mechanisms in the treatment of AAA. Firstly, we collected 202 API-related therapeutic targets and 2475 AAA-related pathogenetic targets. After removing duplicates, a total of 68 potential therapeutic targets were obtained. Moreover, 5 targets with high degree including TNF, ACTB, INS, JUN, and MMP9 were identified as core targets of API for treating AAA. In addition, functional enrichment analysis indicated that API exerted pharmacological effects in AAA by affecting versatile mechanisms, including apoptosis, inflammation, blood fluid dynamics, and immune modulation. Molecular docking results further supported that API had strong affinity with the above core targets. Furthermore, protein level of core targets and related pathways were evaluated in a Cacl2-induced AAA model by using western blot and immunohistochemistry. The experimental validation results demonstrated that API significantly attenuated phosphorylation of JUN and protein level of predicted core targets. Taken together, based on network pharmacological and experimental validation, our study systematically explored associated core targets and potential therapeutic pathways of API for AAA treatment, which could supply valuable insights and theoretical basis for AAA treatment.

This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein-protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.

Traditional Chinese Medicine Network Pharmacology (TCM-NP) is an interdisciplinary discipline that integrates information science, systems biology, network science and pharmacology, providing a systematic research methodology for TCM studies. With the development of artificial intelligence (AI) and multi-omics technologies, TCM-NP has entered a new era and can incorporate multimodal and high-dimensional data in the context of big data to enhance both theoretical foundations and technical capabilities. Despite its advancement, TCM-NP still faces challenges, particularly in ensuring the quality of data and research, as well as achieving more profound scientific discoveries. The field needs further innovation to obtain more precise and biomedically meaningful results. Overall research progress in TCM-NP depends on developing more accurate algorithms together with utilizing higher-quality and larger-scale data. This paper gives a perspective on the trends and characteristics of TCM-NP development and application in the era of AI.

Safflower, phellodendron, scutellaria baicalensis, coptis, and gardenia (SPSCG) are medicinal plants with a wide range of anti-inflammatory and antioxidant effects. However, the related mechanism of SPSCG against hand-foot syndrome (HFS) has yet to be revealed.

To investigate the mechanisms of SPSCG in the treatment of HFS using the Network Pharmacology.

Active ingredients and targets of SPSCG for HFS were screened by the Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction databases. Potential therapeutic targets were collected from the GeneCards and OMIM databases. Subsequently, protein-protein interactions (PPI), Gene Ontology (GO) annotations, and pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to investigate the potential mechanism of the SPSCG in HFS. Then, molecular docking and molecular dynamics simulations were performed to predict the binding interactions between the active compound and the core target. Finally, vitro experiments were used to verify the repair effect of key ingredients of SPSCG on cell damage caused by 5-Fluorouracil.

Quercetin, kaempferol, β-sitosterol, and stigmasterol were identified as the major active components of SPSCG. GO analysis showed a total of 1,127 biological processes, 42 terms cellular components, and 57 molecular functions. KEGG analysis showed that the MAPK, TNF, and IL-17 signaling pathways were significantly enriched. The PPI analysis discovered that EGFR, CASP3, AKT1, CCND1, and CTNNB1 shared the highest centrality among all target genes. The experimental results confirmed that these SPSCG active ingredients could treat HFS by reducing inflammation reaction and promoting cell damage repair.

SPSCG may alleviate HFS by exerting antioxidative effects and suppressing inflammatory responses.

There are numerous uses for the pharmacological effects of thiazolo-pyridine and its derivatives. The main objective of the study was to synthesis 10 novel derivatives of thiazolo[3,2-a] pyridine-6,8-dicarbonitrile with a 22-78% yield, with a focus on their potential anti-diabetic properties. We investigated the interactions between these compounds and the enzyme α-amylase through an in silico study involving molecular docking. According to the docking analysis results, the resulting compounds had advantageous inhibitory properties. With a docking score of -7.43 kcal/mol against the target protein, compound 4e performed best. The stability root-mean-square deviation (RMSD) showed that the complex stabilizes after 25 ns and with minor perturbation at 80. The RMSF values of the ligand-protein complex indicate that the following residues have interacted with compound 4e during the MD simulation: Trp58, Trp59, Tyr62, Gln63, His101, Val107, lle148, Asn152, Leu162, Thr163, Gly164, Leu165, Asp197, Ala198, Asp 236, Leu237, His299, Asp300, and His305. Moreover, the pharmacokinetic and drug-like properties of the synthesized derivatives of 2-arylamino-dihydroindeno[1,2-b] pyrrol-4(1H)-one suggest that they have the potential to be effective inhibitors of α-amylase and should be considered for further research. Nevertheless, it is crucial to ascertain the in vivo and in vitro effectiveness of these compounds through biochemical and structural investigations.

FFBZL is composed of three herbs: Scutellaria barbata D. Don (SBD), Astragali Radix (AR), and Ligusticum chuanxiong Hort (CX). FFBZL has been reported to be effective in the treatment of oral squamous cell carcinoma (OSCC). However, the molecular mechanism involved remains unclear. Based on network pharmacology combined with bioinformatics and molecular docking, the effect and molecular mechanism of action of FFBZL in treating OSCC were explored.

This study employed an integrated approach using various databases and literature sources to identify the effective components of FFBZL, with a specific emphasis on screening active ingredients that align with traditional Chinese medicine principles. The TCMSP, ETCM, and SymMap databases were utilized to collect information on the active constituents and targets of FFBZL, while the PharmMapper database was used to predict targets. Key components were selected based on the degree value of the 'active component-target' network. Transcriptome data for OSCC samples were obtained from the TCGA and GEO databases. Differential gene expression analysis was conducted to identify targets associated with OSCC, and these targets were subsequently aligned with targets of the effective components of FFBZL to identify common targets. Subsequently, the STRING database was utilized to construct a protein‒protein interaction (PPI) network of these common targets, which was subsequently visualized using Cytoscape. Next, 71 targets were rescreened using the PPI network, and GO and KEGG enrichment analyses were performed; the PI3K-Akt signaling pathway was the top-ranking pathway related to cell apoptosis. Next, the expression of 19 genes enriched in the PI3K-Akt signaling pathway was analyzed using OSCC transcriptome data from the TCGA and GEO databases. The targets were subsequently mapped to the PI3K-Akt signaling pathway using the KEGG database, and the GSEA algorithm was used to assess the overall expression trend of the genes in this pathway. The 71 common targets were subsequently imported into the STRING database and visualized using Cytoscape. The DEGREE and MCC algorithms were used to select the corresponding targets within the PPI network. The intersection of these targets and the 19 targets mapped to the PI3K-Akt signaling pathway led to the identification of 6 key targets associated with cell apoptosis: GSK3B, PIK3CA, FN1, MET, SPP1, and MAPK3. Subsequently, the UALCAN database was utilized to analyze the expression levels and survival associations of the key genes related to cell apoptosis, and the transcriptome data from the GEO database were used to assess the correlations among the 6 key genes. Finally, molecular docking studies were conducted to explore the relationships between these targets and the active components with predicted associations.

This study identified six key components of FFBZL (quercetin, wogonin, carthamidin, scutellarein, senkyunolide K and astragalosidei: astragaloside I) as well as 820 potential target genes of these components. Intersection of these targets with those related to OSCC yielded 151 common targets. GO and KEGG enrichment analyses revealed that most of the top-ranked functions and pathways were associated with apoptosis, with the PI3K-Akt signaling pathway playing a critical role. Transcriptome analysis of data from the TCGA and GEO databases indicated that the genes enriched in the PI3K-Akt signaling pathway were strongly upregulated, and the GSEA algorithm indicated an overall upregulation trend for the PI3K-Akt signaling pathway. By intersecting the targets with the 19 genes mapped to the PI3K-Akt signaling pathway using the DEGREE and MCC algorithms, six key targets related to cell apoptosis were identified. The mRNA and protein expression levels of most these targets in head and neck squamous cell carcinoma were higher than those in normal tissues. Survival analysis revealed that low expression of SPP1 and FN1 was associated with increased patient survival time. Additionally, the molecular docking results indicated strong binding potential between the six identified key components and the six key targets.

Network pharmacology is an emerging interdisciplinary research method. The application of network pharmacology to reveal the nutritional effects and mechanisms of active ingredients in food is of great significance in promoting the development of functional food, facilitating personalized nutrition, and exploring the mechanisms of food health effects. This article systematically reviews the application of network pharmacology in the field of food science using a literature review method. The application progress of network pharmacology in food science is discussed, and the mechanisms of functional factors in food on the basis of network pharmacology are explored. Additionally, the limitations and challenges of network pharmacology are discussed, and future directions and application prospects are proposed. Network pharmacology serves as an important tool to reveal the mechanisms of action and health benefits of functional factors in food. It helps to conduct in-depth research on the biological activities of individual ingredients, composite foods, and compounds in food, and assessment of the potential health effects of food components. Moreover, it can help to control and enhance their functionality through relevant information during the production and processing of samples to guarantee food safety. The application of network pharmacology in exploring the mechanisms of functional factors in food is further analyzed and summarized. Combining machine learning, artificial intelligence, clinical experiments, and in vitro validation, the achievement transformation of functional factor in food driven by network pharmacology is of great significance for the future development of network pharmacology research.

As a traditional tonic Chinese medicine, Polygonum multiflorum is widely used in clinical practice. However, with the deepening of modern pharmacological research, its drug toxicity, especially hepatotoxicity, has become increasingly prominent. Based on a large number of clinical and experimental evidence, it has been confirmed that Polygonum multiflorum and its main active ingredients such as anthraquinones and diphenylethylene glucoside can cause different degrees of hepatotoxicity. Further studies have shown that the toxicological mechanisms involved in the hepatotoxicity of different extracts and components of Polygonum multiflorum may include oxidative phosphorylation, bile acid excretion, different metabolic pathways, genetic and metabolic factors, immune homeostasis, etc. By sorting out and summarizing the literature related to hepatotoxicity of Polygonum multiflorum in recent years, this paper discussed the hepatotoxicity mechanism of Polygonum multiflorum and its main components and some contradictions in related reports.

Orostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown.

We used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation.

Drosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds.

We demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE.

In summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.