Network Pharmacology Research Articles

Regulation of the Nrf2/HO-1 pathway in chronic obstructive pulmonary disease-induced muscle atrophy using Jinshui Liujian decoction and Bajitian pills: insights from network pharmacology and animal models

Abstract Objective This study aimed to investigate the therapeutic effects of the combination of modified Jinshui Liujian decoction and Bajitian pills (TCM) on chronic obstructive pulmonary disease (COPD)-induced muscle atrophy using network pharmacology and animal model experiments. Methods Network pharmacology technique has been employed to analyze the potential targets of TCM on treating COPD. In vivo, COPD mice model was induced by lipopolysaccharide (LPS) combined with smoke treatment. To comparing the protective effects of TCM on this disease, these parameters including general condition, serum inflammatory factors, protein expression levels, gene copies, and histopathological changes in the lungs and gastrocnemius muscle mass have been further assessed in mouse in different groups. Results Network pharmacology analysis identified 203 intersecting targets, primarily associated with apoptosis, phosphorylation, and inflammatory response. Animal experimental demonstrated that TCM could significantly improve the decreased skeletal muscle mass (p < 0.001), abnormal histopathologic morphology, decreased superoxide dismutase (SOD, p < 0.05), increased levels of serum malondialdehyde (MDA, p < 0.001) and tumor necrosis factor-α (TNF-α, p < 0.001) as compared to model group. Further mechanism exploration showed that a significant increase on the gene and proteins levels of nuclear factor erythroid 2-related factor 2 (NRF2, p < 0.05) and heme oxygenase-1 (HO-1, p < 0.05) have been observed in TCM-treated animals compared with that of in model animals. Interestingly, some indicators (serum MDA/SOD/TNF-α, RNA and protein levels of NRF2 and HO-1) showed more positive changes in TCM combined with western medicine (TCM-WN) - treated animals compared with that of TCM-treated animals. Conclusion Modified Jinshui Liujian decoction and Bajitian pills effectively mitigate muscle atrophy associated with COPD by modulating the Nrf2/HO-1 pathway through multi-target mechanisms. The combined TCM and WM therapy demonstrates enhanced therapeutic efficacy compared to monotherapy.

Dendrobium huoshanense polysaccharide inhibits NSCLC proliferation and immune evasion via FXR1-IL-35 axis signaling pathway

Abstract Dendrobium huoshanense has received special attention for its advantages in the treatment of lung cancer, but the underlying molecular mechanisms are not yet well understood. First, we obtained 8 active ingredients and 159 effective action targets of Dendrobium huoshanense using network pharmacology, and searching target interactions through STRING, constructing the PPI network and KEGG, GO and Hallmark enrichment analysis. Then, we combined target’s enrichment analysis and GSEA enrichment analysis of IL-35, indicating the mechanism of cDHPs for non-small cell lung cancer (NSCLC) may be related to tight junction and NSCLC pathway. Further, FXR1 and ACTR3 were identified as core therapeutic targets, and high expression of FXR1 or ACTR3 was significantly associated with poor prognosis of patients. The analysis of single-cell data also indicated that the percentage of CD4-CTLA4-Treg cells may be increased by the expression of IL-35, resulting in a suppressive immune microenvironment. Next, In vivo experiment, we detected iTr35 by flow cytometry, detected IL-35 level by RT-PCR, Western blotting and ELISA, and detected NK cell activity to explore the immunomodulatory effects and anti-tumor mechanism of cDHPs. After cDHPs administration, the conversion of CD4+ T cells to iTr35 is inhibited, p35 and EBI3 in both protein and mRNA levels, the levels of IL-35 and IL-4 in serum decreased. The levels of IFN-γ, while the activity of NK cells in mice increased, enhancing the anti-tumor immune effect of the organism. Finally, analysis of sequencing data from the immunotherapy cohort of tumor-bearing mice obtained from the TISMO database shows that the combination of cDHPs and PD-1/PD-L1 antibodies improves effector and thus PD-1/PD-L1 antibody efficacy. These findings suggest that cDHPs inhibit NSCLC proliferation and immune escape via the FXR1-IL-35 axis signaling pathway. Graphical abstract

A network pharmacological target mendelian randomization study on the neuroprotective effects ofactive ingredients in mahuang fuzi xixin decoction for multiple sclerosis.

Mahuang Fuzi Xixin Decoction (MFX), a traditional Chinese medicine containing 44 volatile components (97.36% total oil), includes key compounds like α-terpenol (13.34%) and 1,2,3-trimethoxy-5-methyl-benzene (22.64%). Using network pharmacology and Mendelian randomization, 24 active compounds were identified targeting MS-related pathways (NF-κB, NLRP3, Toll-like receptor). Genetic variants in CYP450, GSK3B, CYBB, and PON1 correlated with reduced MS risk. In EAE mice, MFX decreased spinal GSK-3B expression (immunofluorescence) and pro-inflammatory factors (ELISA), demonstrating neuroprotection via anti-inflammatory, antioxidative mechanisms and restored GSK-3B levels, highlighting therapeutic potential for MS.

Combining network pharmacology and experimental verification to explore the inhibitory effects of Deoxyelephantopin (DET) Against Non-Small Cell Lung Cancer (NSCLC)

Combining network pharmacology and experimental verification to explore the inhibitory effects of Deoxyelephantopin (DET) Against Non-Small Cell Lung Cancer (NSCLC)

Exploration potential sepsis–ferroptosis mechanisms through the use of CETSA technology and network pharmacology

As an important self-protection response mechanism of the body, inflammation can not only remove the necrotic or even malignant cells in the body, but also take a series of targeted measures to eliminate the pathogen of foreign invasion and block the foreign substances that may affect the life and health of the body. Flavonoids have known anti-inflammatory, anti-oxidation, anti-cancer and other effects, including glycyrrhizin molecules is one of the representatives. Licochalcone D has known anti-inflammatory and antioxidant properties and is effective in the treatment of a variety of inflammatory diseases. However, the underlying mechanism for the treatment of sepsis remains unclear. In this study, the therapeutic potential of Licochalcone D for sepsis was studied by analyzing network pharmacology and molecular dynamics simulation methods. Sepsis-related genes were collected from the database to construct PPI network maps and drug-targeting network profiles. The potential mechanism of Licochalcone D in sepsis was predicted by gene ontology, KEGG and molecular dynamics simulation. Sixty drug-disease genes were subsequently validated. Go analysis showed that monomeric small molecule Licochalcone D could regulate the process of intracellular enzyme system. The KEGG pathway analysis showed that the signal pathway of the main effect was related to the calcium pathway. The results of intersections with iron death-related target genes showed that ALOX5, ALOX15B and other nine targets all had the effect of possibly improving sepsis, while GSE 54,514, GSE 95,233 and GSE 69,528 were used to analyze the survival rate and ROC curve. Five genes were screened, including ALOX5, ALOX15B, NFE2L2 and NR4A1, HIF1A. The results of molecular docking showed that ALOX5 and Licochalcone D had strong binding activity. Finally, the results of molecular dynamics simulation showed that there was good binding power between drug and target. In the present study, we utilized molecular dynamics simulation techniques to assess the binding affinity between the small-molecule ligand and the protein receptor. The simulation outcomes demonstrate that the binding interface between the ligand and receptor remains stable, with a calculated binding free energy (ΔG) of -32.47 kJ/mol. This signifies a high-affinity interaction between the ligand and receptor, suggesting the long-term stability of the small molecule under physiological conditions. These findings provide critical insights for drug development efforts. This study elucidates the therapeutic potential of Licochalcone D, a traditional Chinese medicine monomer, in improving sepsis through the regulation of ferroptosis, thereby providing a new direction and option for subsequent clinical drug development in the treatment of sepsis.

Integration of network pharmacology, molecular docking and pharmacokinetic investigations of dandelion in rats for the treatment of diabetes mellitus.

Integration of network pharmacology, molecular docking and pharmacokinetic investigations of dandelion in rats for the treatment of diabetes mellitus.

Gut microbial metabolites targeting JUN in renal cell carcinoma via IL-17 signaling pathway: network pharmacology approach.

The gut microbiome plays a crucial role in renal diseases, influencing conditions such as renal cell carcinoma (RCC), acute kidney injuries, and diabetic nephropathy. Recent studies highlight the association between gut microbial metabolites (GMM) and RCC progression. This study employs a computational network pharmacology framework to explore the mechanistic action of gut microbiota-derived metabolites against RCC. GMM were selected from the gutMgene database and analyzed for common targets using DisGeNET, Gene Card, and OMIM. Downstream analysis included gene ontology, KEGG pathway enrichment, metabolite-target-pathway-disease network construction, and protein-protein interaction analysis. Further, key metabolites were evaluated for drug-likeness, ADMET properties, and molecular docking, followed by molecular dynamics simulations (MDS) to assess complex stability. The JUN/AP-1 gene emerged as the prime target, exhibiting the highest binding affinity with Icaritin (-5.9kcal/mol), followed by Quercetin and Luteolin. MDS confirmed the stable binding of Icaritin to the active site throughout the simulation. These GMM may influence anticancer activity through distinct regulatory pathways involving the JUN/AP-1 gene, either by inhibiting or modulating its function. These insights establish a basis for further in vitro and in vivo investigations, supporting the development of microbiome-based therapeutic approaches.

Exploring the Comorbidity Mechanism among Functional Diarrhea, Irritable Bowel Syndrome with Predominant Diarrhea, and Functional Dyspepsia through the Gut-brain Axis and the Pharmacological Mechanisms of Shen-Ling-Bai-Zhu-San Therapy.

Functional Diarrhea (FDr), Irritable Bowel Syndrome with predominant diarrhea (IBS-D), and Functional Dyspepsia (FD) are common functional gastrointestinal disorders (FGIDs) with significant impacts on quality of life. While the gut-brain axis and key regulators like 5-hydroxytryptamine (5-HT), dopamine (DA), and butyrate are known to play crucial roles in these conditions, the mechanisms underlying their comorbidities remain unclear. Shen-Ling-Bai-Zhu-San (SLBZS), a traditional herbal formula, is effective in treating FGIDs. Still, the specific components and mechanisms mediating its therapeutic effects via the gut-brain axis are not well understood. This study identified molecular links among FDr, IBS-D, and FD from the gut-brain axis using integrated biological information. The pharmacological mechanisms of SLBZS were explored through network pharmacology, molecular docking, molecular dynamics simulations, and in vitro bio-layer interferometry (BLI) validation. A total of 328 common targets were identified among FDr, IBS-D, and FD, with 22 hub genes in the protein-protein interaction (PPI) network associated with 5-HT/DA/butyrate pathways. Virtual screening revealed seven key targets (AKT1, CASP3, VEGFA, INS, CTNNB1, PTGS2, and IL1B) and 14 bioactive components (e.g., diosgenin and luteolin) from SLBZS. Molecular docking indicated strong binding affinities between key components and targets, while molecular dynamics simulations confirmed stable interactions, particularly between PTGS2 and diosgenin/luteolin. BLI experiments further validated the strong binding affinity of PTGS2 for diosgenin. This study elucidates potential targets shared by FDr, IBS-D, and FD through the gut-brain axis, highlighting diosgenin's interaction with PTGS2 as a potential mechanism of SLBZS's therapeutic effects. These findings provide valuable insights into the pharmacological mechanisms of SLBZS in treating FGIDs and suggest new avenues for targeted therapies.

Phytochemical analysis of leaf extract of Piper nigrum and investigation of its biological activities.

This study investigates the phytoconstituents of the less explored leaf of Piper nigrum, a common ethnomedicinal plant as an alternate source for multiple bioactivities. Hydro-ethanolic (1:4) extract of Piper nigrum leaves (PNLE) prepared and profiled using liquid chromatography and mass spectrometryfor identification ofphytomolecules. Anti-oxidant activity, intracellular reactive oxygen species (ROS) expression, phagocytosis activity, and cytokine expression were estimated using cell-free and cell-based assays. Anti-cancer activity was determined with cancer cell viability, migration inhibition and colony-formation assay. Apoptosis and membrane depolarizationassay were done using fluorescent microscopic staining methodswhile network pharmacology, and molecular docking analysis were done using open source and online tools. Major phytomolecules identified in PNLE were pentanamide N,N-didecyl, piperettine, curcumin, myristicin, pipernonaline, sesamin, and lupenone. PNLE exhibited anti-bacterial activity with higher activity against Gram-positive bacteria, Staphylococcus aureus. PNLE also showed anti-oxidant and anti-inflammatory activity through neutralization of free radicals; inhibition of intracellular ROS generation; inhibition of phagocytosis and reduction of cytokine (IL-6 and TNF-α) levels. PNLE showed anti-proliferative activity against human breast cancer cells (MDA-MB-231), rat mammary tumor cells (LA7), and mouse melanoma cells (B16-F10) with highest activity against MDA-MB-231 cells. The extract did not inhibit human kidney cells (HEK-293). Further, PNLE treatment significantly inhibited cell migration and colony formation of MDA-MB-231 cells. Fluorescent staining techniques confirmed induction of apoptosis in cancer cells by PNLE. Further, network pharmacology and molecular docking studiesrevealed that the identifiedPNLE phytomolecules share 97 targets of out of potentialbreast cancer and inflammation-related targetgenes with four bestcommon targetproteinsamong thetop hub genes and sesamin showed the highest binding affinity with theseimportant cellular targets. Overall, the phytochemical profile of PNLE showed clear presence ofimportant phytomolecules and their association with critical human cellular mechanistic pathways responsible for exhibited bioactivities. This study further establishes the leaf of P. nigrum as an additional anatomical plant part with potentmedicinal propertiesand as apotential renewable source for bioactive phyomolecules.

Mechanistic study of Lonicerae Japonicae Flos (Caprifoliaceae) in non-small cell lung cancer prevention and treatment through integrative pharmacology, multi-machine learning, artificial intelligence, and in vitro experiments.

Mechanistic study of Lonicerae Japonicae Flos (Caprifoliaceae) in non-small cell lung cancer prevention and treatment through integrative pharmacology, multi-machine learning, artificial intelligence, and in vitro experiments.

Unveiling the therapeutic potential of HZQYF: exploring the inhibitory impact of a clinical herbal formula on gastric cancer through network pharmacology and transcript analysis

Hezi Qingyou Formula (HZQYF) is a clinical formulation known for its efficacy in treating gastrointestinal diseases. Nevertheless, its specific impact and underlying mechanism of action in gastric cancer remain to be fully elucidated. The major components of the formula were precisely identified and characterized using ultra-high-performance liquid chromatography coupled with a tandem mass spectrometer (UHPLC-MS/MS). Network pharmacology and transcript analysis were utilized to identify the targets associated with drug-disease interactions. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses were conducted to unravel the pivotal pathways involved. Furthermore, in vitro experiments were performed to validate the anti-gastric cancer activity of HZQYF, including assessments of cell viability and clonogenic potential. These results revealed that 260 co-expressed targets were identified as shared between HZQYF and gastric cancer. These genes were significantly enriched in biological processes and pathways related to steroid metabolism, gamma-aminobutyric acid (GABA)-A receptor complex, steroid binding activity, extracellular ligand-gated ion channel activity, chemical carcinogenesis-reactive oxygen species, and GABAergic synapse. Furthermore, the principal components of the formula were characterized. Subsequent cell experiments confirmed the formula's ability to inhibit gastric cancer activity and suppress colony formation in vitro. In conclusion, these findings suggest that Hezi Qingyou Formula may exert its anti-gastric cancer activity by influencing reactive oxygen species and modulating GABAergic synapses in-silico methods. This study provides a foundation for further exploration of HZQYF as a potential therapeutic agent for gastric cancer.

Uncovering the anti-cancer mechanism of cucurbitacin D against colorectal cancer through network pharmacology and molecular docking

Colorectal cancer is a significant global health challenge due to chemoresistance, necessitating new treatments. Cucurbitacin D, with its anti-cancer properties, shows promise, but its effects on colorectal cancer are not well understood. We investigated the impact of cucurbitacin D on colorectal cancer cell lines using MTT assays and Annexin V/7-AAD staining followed by flow cytometry for apoptosis analysis. Public databases helped identify cucurbitacin D and colorectal cancer-related gene targets for network pharmacology analysis. Protein–protein interaction networks were constructed using STRING and analyzed in Cytoscape. Gene ontology and KEGG pathway enrichment analyses were performed using ClueGo. Molecular docking studies were conducted via Autodock Vina and visualized in Discovery Studio. Western blot assessed protein expression changes in key targets under cucurbitacin D. Cucurbitacin D dose-dependently reduced colorectal cancer cell viability and induced apoptosis. Network pharmacology pinpointed crucial targets like STAT3, AKT1, CCND1, and CASP3. Molecular docking confirmed strong interactions with these targets. Enrichment analysis highlighted involvement in the 'PI3K-AKT,' 'JAK-STAT,' and 'ErbB' signaling pathways. These findings suggest cucurbitacin D as a potential anti-colorectal cancer agent, demonstrating significant effects on cell viability and apoptosis, and engaging critical cancer-related pathways, making it a promising candidate for further colorectal cancer therapeutic research.

Anti-inflammatory activity of Curcuma wanenlueanga Saensouk, Thomudtha & Boonma rhizomes and the search for its bioactive markers by harmonizing bioassay-guided isolation and network pharmacology

BackgroundRhizomes of Curcuma wanenlueanga Saensouk, Thomudtha & Boonma have been used in Thai traditional medicine and are included as an ingredient in a Thai traditional liniment formula listed by the Ministry of Public Health of Thailand for treating symptoms related to joints and muscle inflammation. However, anti-inflammatory activity and bioactive constituents of C. wanenlueanga have not yet been investigated. Thus, this study aimed to investigate the anti-inflammatory activity and underlying mechanism of C. wanenlueanga rhizome extract and its responsible bioactive components.MethodsThe fractionation of bioactive compounds from C. wanenlueanga extract was guided by antioxidant activity on DPPH and Griess assays, and anti-inflammatory activity on LPS-induced RAW 264.7 cells. The biological activities of isolated compounds were first predicted by network pharmacology and further confirmed in cell-based assay with LPS-induced RAW 264.7 cells and enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6).ResultsThe ethanolic extract of C. wanenlueanga rhizomes was proved to show anti-inflammatory activity on LPS-induced RAW 264.7 cells. Three curcuminoids including curcumin (1), demethoxycurcumin (2), dihydrodemethoxycurcumin (3), and two sesquiterpenoids, namely curcumenone (4), and zedoarondiol (5) were separated from anti-inflammatory fractions of C. wanenlueanga extract. The anti-inflammatory activity of these compounds to attenuate the productions of TNF-α and IL-6 was predicted by pharmacological network. The inflammatory assays, including the Griess assay for NO and ELISA for TNF-α and IL-6, confirmed that all isolated compounds reduced the production of these inflammatory mediators.ConclusionThe present study shows the accordance between the results from pharmacological network and cell-based assays, which indicate the anti-inflammatory activity of C. wanenlueanga rhizomes and their bioactive constituents. This suggests the potential of bioactive compounds 1–5 to be used for quality assessment of C. wanenlueanga extract in the development of herbal products.

Mechanistic and metabolic exploration of neohesperidin against lung cancer cell lines through ROS-mediated mitochondrial apoptosis: An in-silico and in-vitro approach.

Mechanistic and metabolic exploration of neohesperidin against lung cancer cell lines through ROS-mediated mitochondrial apoptosis: An in-silico and in-vitro approach.

Investigating Network and Experimental Effect of Silibinin on Lipin-1 and Lipin-2 Gene Expression during Ischemia-reperfusion of the Liver in Rats.

This study aims to investigate the impact of silibinin (SILI) on the expression of the Lipin-1 and Lipin-2 genes during warm ischemia-reperfusion (I/R) of the liver. Network pharmacology was employed to identify potential targets of SILI in the context of liver inflammation and to elucidate the mechanism underlying the regulation of Lipin gene expression. The rats were allocated into four groups, each comprising eight individuals: vehicle group: These rats underwent a median laparotomy, and were administered normal saline. (2) SILI group: Rats in this group received 50 mg/kg of SILI after laparotomy. (3) I/R group: Rats in this group experienced I/R and were administered normal saline. (4) I/R+SILI group: In this group, rats were treated with SILI in conjunction with the I/R procedure. Western and real-time PCR were used to measure protein levels, and assess Lipin-1 and Lipin-2 gene expression. The analysis identified 18 shared targets between SILI (Severe Acute Liver Injury) and liver inflammation, linking them to 107 KEGG pathways, with the mTOR signaling pathway standing out as a critical connection to Lipin. Docking studies of targets in the mTOR signaling pathway revealed binding energies of -9.7 kcal/mol for PIK3CA and -10.4 kcal/mol for mTOR protein. Furthermore, the protein level and gene expression of Lipin-1 and Lipin-2 genes were significantly elevated during I/R compared to the vehicle group (P < 0.001). However, SILI was observed to reduce their expression during I/R (P < 0.05). The beneficial effects of SILI can be attributed to the modulation of Lipin-1 and Lipin-2 gene expression during I/R, which is likely one of the mechanisms underlying its beneficial effects during I/R.

Isorhapontigenin: exploring a promising resveratrol analog for disease management through diverse signaling pathways-a review with computational insights.

Plants are a meticulous sourceof biologically active substances that have positive health effects. Recent studies demonstrated the existence of Isorhapontigenin, a stilbene derivative,differs by its methoxylation pattern but shares a structure identical to resveratrol. Through a review of the literature and an in silico interpretation, the current review will be centeredon the anti-inflammatory, anti-cancer, anti-obesity, and other medicinal properties of Isorhapontigenin. The Gnetum genus has species that have a very significant amount of Isorhapontigenin, such as Gnetum parvifolium. Tropical zones of Africa, Asia, and South America are home to the majority of the Gnetaceae family. Several investigations have reported the compound's benefits for health. Isorhapontigenin is very effective against anti-inflammatory, anticancer, antibacterial, antifungal, neuroprotective, antiviral, and antioxidant effects andcould be a possible treatmentdrug. Using network pharmacology (ADME, Networking and Docking), the bioavailability of compound about disorders was examined. KeGG analysis and gene ontology (GO) demonstrated that Isorhapontigenin works via many immune system and cancer pathways. Human COX-1 receptor protein 6Y3C and receptor protein 1CX2 that had the best fit with the drug were used for docking analysis: Docking scores of - 8.2 and - 8.4 for Isorhapontigenin, respectively. In conclusion, Isorhapontigenin is a novel compound in the context of drug development.

Molecular Mechanisms of Reversal of Multidrug Resistance in Breast Cancer by Inhibition of P-gp by Cytisine N-Isoflavones Derivatives Explored Through Network Pharmacology, Molecular Docking, and Molecular Dynamics

Molecular Mechanisms of Reversal of Multidrug Resistance in Breast Cancer by Inhibition of P-gp by Cytisine N-Isoflavones Derivatives Explored Through Network Pharmacology, Molecular Docking, and Molecular Dynamics

Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathway

ObjectiveColorectal cancer (CRC), as a highly prevalent malignant tumor globally, faces the dual challenges of drug resistance of cancer stem cells and immune escape in its treatment. Although the traditional Chinese medicine Yigong San (YGS) shows potential in improving the clinical adverse reactions of CRC, its core active components and mechanism of action remain unclear. Based on network pharmacology screening, this study for the first time discovered that Gomisin B might regulate the progression of CRC through the Toll-like receptor 4/Nuclear Factor-kappa B (TLR4/NF-κB) signaling pathway, and aimed to systematically reveal the molecular mechanisms by which YGS and Gomisin B inhibited the malignant phenotypes and immune escape of CRC cells.MethodsThe The Cancer Genome Atlas (TCGA) database was integrated with network pharmacology analysis to screen for the key target of CRC, Gomisin B, and its associated TLR4/NF-κB pathway. Through in vitro CRC stem cell models and mouse xenograft tumor models, techniques such as CCK-8, Transwell, flow cytometry, qPCR/WB were used to evaluate the effects of YGS and Gomisin B on proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT), and to detect the expression of TLR4 and downstream inflammatory factors.ResultsBoth YGS and Gomisin B inhibited the proliferation, migration and invasion of CRC stem cells and tumor tissues. Meanwhile, they promoted apoptosis but reduced the expression of the inflammatory factor TLR4 and proteins associated with the NF-κB pathway, thereby exerting suppressive effects on tumorigenesis and disease progression. YGS might also impede EMT progression through modulation of the NF-κB pathway.ConclusionThis study for the first time elucidated the dual anti-tumor mechanisms of YGS, which sensitized CRC stem cells and inhibited immune escape by targeting the TLR4/NF-κB pathway through Gomisin B. It provides a pharmacological basis for the modern research of traditional Chinese medicine compound against CRC.Clinical trial numberNot applicable.

20-Acetylsinularolide B (ASB) from Lobophytum crassum Exhibits Anti-Cancer Activity in vitro through IGF1R/PI3K/AKT/mTOR Pathway.

As lung cancer remains the leading cause of cancer-related deaths worldwide, the development of novel therapeutic drugs is essential. 20-Acetylsinularolide B (ASB) is a diterpene isolated from marine soft coral Lobophytum crassum. Our previous studies demonstrated that ASB exhibits growth-inhibitory effects on non-small cell lung cancer (NSCLC) cells. This study employed network pharmacology to predict ASB's potential targets in NSCLC treatment. The predicted target was validated using the cellular thermal shift assay (CETSA). In vitro anticancer activity was assessed through MTT and crystal violet assays for proliferation, along with Western blotting, cell cycle and apoptosis analysis, mitochondrial membrane potential, ROS levels, and nuclear morphology evaluation. Migration and invasion were evaluated using wound healing and Transwell assays.The results showed that ASB significantly arrests the cell cycle of H1299 cells at the G2/M phase by modulating the IGF1R/PI3K/AKT/mTOR signaling pathway, thereby inhibiting cell mitosis. Simultaneously, ASB promoted intracellular reactive oxygen species (ROS) production, reduced mitochondrial membrane potential, and ultimately induced cell apoptosis. Additionally, ASB significantly inhibited the colony formation, migration, and invasion abilities of H1299 cells, which are closely associated with the function of IGF1R target. These findings highlight the significant potential of ASB as a lead anticancer compound for NSCLC therapy.

Effects of Asiatic acid on brain cancer by altering astrocytes and the AKT1-PRKCB signaling pathway: A genomic and network pharmacology perspective.

Effects of Asiatic acid on brain cancer by altering astrocytes and the AKT1-PRKCB signaling pathway: A genomic and network pharmacology perspective.