Luteolin inhibits diffuse large B-cell lymphoma cell growth through the JAK2/STAT3 signaling pathway

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 20, 2025

Luteolin, a flavonoid present in botanical drugs, plants, and dietary sources, has demonstrated anticancer properties against various tumors, yet its role diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to uncover the molecular mechanism of luteolin DLBCL treatment using combination vitro vivo experiments computational analysis. Human cell lines U2932 OCI-LY10 were utilized assess luteolin's impact on growth, apoptosis, cycle progression, modulation JAK2/STAT3 pathway proteins. In vivo, tumor-bearing nude mice model was employed evaluate antitumor efficacy effects protein expression. Additionally, dynamics simulations conducted explore interaction between JAK2. The findings revealed that significantly suppressed proliferation, induced arrested at G2/M phase both lines. mouse model, effectively inhibited tumor growth downregulated expression phosphorylated JAK2 STAT3 without altering total levels STAT3. Computational analysis indicated stable binding Collectively, these results suggest anti-DLBCL activity may be mediated through regulation signaling pathway, positioning it as potential therapeutic agent for DLBCL.

Язык: Английский

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Dihydrotanshinone I Attenuates Diet‐Induced Nonalcoholic Fatty Liver Disease via Up‐Regulation of IRG1

Phytotherapy Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is the most common chronic disease, but effective therapeutic drugs are still lacking. Dihydrotanshinone I (DHTS), a natural product isolated from Salvia miltiorrhiza , has been shown to have ameliorative effects on NAFLD. The aim of this study was investigate hepatoprotective effect DHTS NAFLD and its mechanism. A model treatment established using Western diet observe NAFLD, which were detected by immunohistochemical, immunofluorescence, other experiments. mechanism further explored constructing immune responsive gene 1 (IRG1) knockout mice, RNA sequence, molecular docking. results revealed that significantly improved diet‐induced metabolic disorders in notably alleviating inflammation, oxidative stress, fibrosis. Further analysis intervention associated with activation IRG1. Subsequent experiments confirmed IRG1 deletion reversed above protective Mechanistically, enhanced antioxidant nuclear factor–erythroid 2‐related factor 2 (Nrf2) pathway through IRG1/itaconate blocked stress response liver. In addition, also inhibited NACHT‐, leucine‐rich repeat (LRR)–, pyrin domain (PYD)–containing protein 3 (NLRP3) inflammasome via IRG1/itaconate, blocking inflammatory amplification suggests may be potential drug for exerts regulatory mainly pathway.

Язык: Английский

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Optimal compatibility proportional screening of Trichosanthis Pericarpium - Trichosanthis Radix and its anti - Inflammatory components effect on experimental zebrafish and coughing mice

Journal of Ethnopharmacology, Год журнала: 2023, Номер 319, С. 117096 - 117096

Опубликована: Авг. 25, 2023

Язык: Английский

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Clozapine Induces Agranulocytosis via Inflammatory and Hematopoietic Cytokine Induction of the JAK–STAT Signaling Pathway: Evidence From Network Pharmacology and Molecular Docking

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(1)

Опубликована: Янв. 1, 2025

ABSTRACT Background Clozapine exhibits significant therapeutic efficacy in schizophrenia, especially treatment‐resistant schizophrenia. However, clozapine can cause agranulocytosis, a fatal adverse effect, and the aim of this study is to explore mechanism based on network pharmacology molecular docking. Method Six two databases were used identify targets associated with respectively. The bioinformatics online platform was overlaps between drug disease targets. protein–protein interaction (PPI) characterized using Cystoscope 3.10.1 STRING. Kyoto Encyclopedia Genes Genomes (KEGG) Gene Ontology (GO) analyzed DAVID platform. A drug‐target‐pathway‐disease constructed utilizing 3.10.1. Auto Dock Vina PyMOL software verify docking core Results analysis revealed 188 overlapping PPI KEGG enrichment pathway analyses demonstrated that induces agranulocytosis by modulating hematopoietic cell lineage JAK–STAT signaling pathways via interleukin‐3 (IL3), IL6, IL2 receptor subunit alpha (IL2RA), granulocyte colony‐stimulating factor. Binding energies favorable (< −7.0 kcal/mol). Conclusion Clozapine‐induced may be linked inflammatory through hematopoietic‐related cytokines. Our findings enhance our comprehension potential mechanisms underlying clozapine‐induced agranulocytosis.

Язык: Английский

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Integrative genetics and multiomics analysis reveal mechanisms and therapeutic targets in vitiligo highlighting JAK STAT pathway regulation of CTSS

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 17, 2025

Vitiligo is a complex autoimmune disease characterized by the loss of melanocytes, leading to skin depigmentation. Despite advances in understanding its genetic and molecular basis, precise mechanisms driving vitiligo remain elusive. Integrating multiple layers omics data can provide comprehensive view pathogenesis identify potential therapeutic targets. The study aims delineate using an integrative multiomics strategy. We focus on exploring regulatory influence JAK/STAT pathway Cathepsin S, target vitiligo. Our GWAS-meta analysis pinpointed five druggable genes: ERBB3, RHOH, CDK10, MC1R, NDUFAF3, underwent drug exploration docking. SMR linked CTSS, CTSH, STX8, KIR2DL3, GRHPR through pQTL eQTL associations. Microarray single-cell RNA-seq showed differential expression CTSS STAT1/3 patients' blood lesions. offers novel perspectives vitiligo's highlighting pathway's role regulating for antigen processing melanocytes. Further research needed confirm these results assess related genes.

Язык: Английский

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Qingfei Jiedu Huatan Formula Inhibits NLRP3 Inflammasome Activation to Attenuates Inflammation and Pyroptosis in Severe Pneumonia: Integrating Experimental Verification, Network Pharmacology and Transcriptomics

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119449 - 119449

Опубликована: Фев. 1, 2025

Язык: Английский

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Strategies for Reducing the Homogenization Phenomenon in the Screening of Key Components in Network Pharmacology Based on the Detectability of Components

Rapid Communications in Mass Spectrometry, Год журнала: 2025, Номер 39(12)

Опубликована: Март 25, 2025

The ingredients of traditional Chinese medicine (TCM) are complex and diverse often identified using the TCM systems pharmacology (TCMSP) database. However, in this database exhibit significant homogeneity, which limits comprehensive understanding TCM's ingredient diversity biological activity. Consequently, liquid chromatography-mass spectrometry (LC-MS) has become a key tool for precise identification components. In study, LC-MS was used to identify components herb. were then compared with component data TCMSP A network pharmacological prediction subsequently performed. An analysis four herb formula prescriptions (Ganmai Dazao decoction, Bazhen granule, Shaoyao Gancao Zixue san) conducted, revealing discrepancies between results found be highly homogeneous. This study underscores pivotal function TCM, particularly addressing issues homogeneity. employment technology enhances precision streamlines potential pharmacodynamic ingredients, thereby propelling toward more contemporary standing.

Язык: Английский

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Anti-vitiligo Mechanisms of Traditional Chinese Medicine Compound Baqia Danshen Liniment: Network Pharmacology, Molecular Docking, and Animal Model Insights

Pharmacognosy Magazine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Background Vitiligo is a skin condition characterized by depigmentation and has proven difficult to treat. Traditional Chinese medicine (TCM) offers potential therapeutic alternatives. Compound Baqian Danshen Liniment (CBDL) multicomponent herbal formula used in TCM. This study aimed investigate its mechanism of action treating vitiligo using network pharmacology, molecular docking, animal experiments. Purpose The purpose this was explore the interactions between CBDL components vitiligo-related biological pathways, confirm binding active compounds key protein targets, assess efficacy an model, measure serum levels inflammatory oxidative stress markers treated mice. Methods Network pharmacology utilized pathways. Molecular docking then employed targets. To CBDL, experiments involving mouse model were conducted. Finally, enzyme-linked immunosorbent assay (ELISA) performed Results exerted effects on modulating pathways such as immune response regulation [tumor necrosis factor (TNF) mitogen-activated kinase (MAPK) signaling], melanogenesis (tyrosinase activation), [nuclear erythroid 2-related 2 (Nrf2) pathway], targeting specific proteins like tyrosinase promote melanocyte activity pigmentation. revealed that particularly luteolin, showed strong affinity core including tyrosinase. treatment significantly promoted proliferation, luteolin demonstrated potent activation. In models, vitiligo-affected substantial improvement, with white plaques receding hair follicles regenerating. ELISA results indicated reduced cytokines [TNF-α interleukin (IL)-6] [acetylcholinesterase (AChE), malondialdehyde (MDA), monoamine oxidase A (MAOA)] while enhancing serum. Conclusion exerts through multitarget promotes activity, likely due activation compounds. These findings suggest could be promising alternative for vitiligo, offering insights into TCM managing condition.

Язык: Английский

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Echinatin inhibits the growth and metastasis of Human hepatocellular carcinoma cells through p38 and JNK signaling pathways

Tissue and Cell, Год журнала: 2025, Номер 95, С. 102907 - 102907

Опубликована: Апрель 6, 2025

Язык: Английский

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Integrating Serum Pharmacochemistry With Network Pharmacology to Elucidate the Mechanism of Wushen Decoction in the Prevention and Treatment of Lower Extremity Erysipelas

Biomedical Chromatography, Год журнала: 2025, Номер 39(5)

Опубликована: Апрель 10, 2025

ABSTRACT Lower extremity erysipelas (LEE), a frequently seen skin and soft tissue infection caused predominantly by streptococci, usually presents with fever, erythema pain. Wushen Decoction (WSD), Compound traditional Chinese medicine, has been used historically to treat LEE, though its exact mechanism of action remains unclear. In this study, we explored the therapeutic mechanisms WSD in treating LEE employing combination serum pharmacochemistry, network pharmacology, molecular docking techniques. Initially, using UPLC‐Q‐Exactive Orbitrap‐MS/MS, 39 candidate active compounds rats treated were identified. Subsequently, pharmacology analysis identified 35 overlapping targets between components, 23 related signaling pathways. Further studies have confirmed that key components (rutin, hyperoside luteoloside) possess potential for effective effects core (PTGS 2 TNF). Furthermore, vitro experiments demonstrated significantly downregulated expression PTGS TNF, thereby validating findings providing insights into mechanisms. Results suggested may exert on modulating TNF NF‐kappa B pathway, offering promising approach prevention treatment LEE.

Язык: Английский

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