NETWORK PHARMACOLOGY BASED COMPUTATIONAL STUDY TO INVESTIGATE THE POTENTIAL MECHANISM OF SYZYGIUM CARYOPHYLLATUM AGAINST COLON CANCER

International Journal of Applied Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 161 - 173

Published: Jan. 7, 2025

Objective: Syzygium caryophyllatum, a traditional medicinal plant from the Myrtaceae family, is rich in potential phytoconstituents. Based on its ethnobotanical uses and documented pharmacological activities, present work was conducted to evaluate probable mechanism of action S. caryophyllatum manage colon cancer by integrating network pharmacology computational studies. Methods: The extract prepared Soxhlet extraction method vitro screening performed using Sulforhodamine (SRB) Assay HT 29 cell lines. We have used super-PRED database, Cytoscape analyser tool, string database CytoHubba for performing analysis compounds reported GC-MS analysis. Kyoto Encyclopedia Genes Genomes (KEGG) pathway DAVID databases were gene set enrichment Schrödinger suite Version 11.4's perform Results: has demonstrated significant cytotoxic activity (IC50 value 49.01 µg/ml) identified seventy-six distinct compounds. Gene Ontology (GO) KEGG that shared targets strongly associated with key processes involved cancer. current study Estrogen Receptor Alpha (ESR1), Heat Shock Protein 90 Family Class A Member 1 (HSP90AA1), Mitogen-activated protein kinase 3 (MAP3K), Epidermal Growth Factor (EGFR) Signal transducer activator transcription (STAT3) proteins as essential 5,7-Dihydroxy-2-undecyl-4H-chromen-4-one, 7a,12-Dihydroindolo[2,3-a] quinolizine, 5-hydroxy-7-methoxy-2-methyl-8-(3-methylbutyl) chromen-4-one Docking studies core completely supplemented their binding affinity suggested strong interactions at site. Conclusion: These outcomes highlight multi-target, multi-compound, multi-pathway approaches against

Language: Английский

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Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Sept. 30, 2023

Abstract Background Spinal cord injury (SCI), which causes loss of sensory and motor function in the body below level injury, is a devastating disease central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), characterized by increased susceptibility infection further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS an independent risk factor for poor prognosis. predominantly occurs following above T5 levels eventually systemic immune failure, possibly via sympathetic–adrenal medullary axis hypothalamic‒pituitary‒adrenal (HPA) axis. However, mechanism remains unclear. Methods objectives The concentrations adrenocorticotropic hormone cortisol plasma, as well changes sympathetic activity (blood pressure catecholamine plasma), were assessed rats high-level (T3) spinal (T3-SCI) group low-level (T10) (T10-SCI) group. Second, differential regulation gene network between HPA was explored histology multitissue transcriptomics, neuroendocrine–immune associated with elucidated. Results spleen thymus gland, are organs, significantly atrophied T3-SCI group, white pulp atrophied. cortisol, mediated adrenal glands, markedly elevated, but norepinephrine decreased. There no difference expression any groups. transcriptome analysis results showed downregulated differentially expressed genes (DEGs) enriched GO term immunoregulation, indicating splenic impaired after SCI. upregulated DEGs hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, Mapkapk2 ) inflammatory pathways, Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, Chrm2 pathways related inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons neuropeptide changes. glands Ciart, per2, per3, cry1, cry2 secretion circadian rhythm changes, IL7r, rt1-bb, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, IL8 MHC-mediated responses. Conclusions To explore possible underlying SCI-IDS, this study neuroendocrine immunity Progressive neuroinflammation spreads neurotransmission through receptors production inhibited. Disruption connection autonomous disturbance finally hypercortisolemia, leading general suppression peripheral adaptive immunity. Neuraxial nerve inflammation caused persists indefinitely, blocking repair; persistent system-wide immunosuppression periphery infection,

Language: Английский

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Chemical Characterization, Antioxidant, Insecticidal and Anti-Cholinesterase Activity of Essential Oils Extracted from Cinnamomum verum L.

Separations, Journal Year: 2023, Volume and Issue: 10(6), P. 348 - 348

Published: June 9, 2023

This study is aimed at evaluating the potential of essential oil Cinnamomum verum (EOCV) as an antioxidant, insecticide against Callosobruchus maculatus and for its anti-acetylcholinesterase activity. To this end, EOCV was extracted via hydrodistillation from plant, identification phytochemicals performed using gas chromatography–mass spectrometry (GC–MS). The antioxidant power determined in vitro tests, insecticidal ability tested exposing C. to EOCV, molecular docking used evaluate anti-cholinesterase ability. results these GC–MS analyses show that main composition comprises Cinnamaldehyde dimethyl acetal (64.50%), cinnamicaldehyde (35.04%) α-Copaene (0.11%). studied OEs, by inhalation test, expressed concentration EOs required death 50% insects (LC50) 95% adults (LC95) after 96 h exposure, 3.99 ± 0.40 14.91 0.10 μL/L air, respectively. In contact exposure gave LC50 LC95 3.17 0.28 8.09 0.05 A comparison activity ascorbic acid DPPH free radical scavenging Ferric Reducing Antioxidant Power (FRAP) revealed IC50 EC50 values be much higher than obtained acid, simulation Coumarin, Piperonal, alpha-Copaene possessing inhibitory activities human acetylcholinesterase. However, further experimental validation needed enhance prospects study.

Language: Английский

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Study on the mechanism of Gastrodiae Rhizoma, Lycii Fructus, and Ziziphi Spinosae Semen in sedation and tranquillising mind

Molecular Diversity, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

Language: Английский

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Structure–Activity Relationship Target Prediction Studies of Clindamycin Derivatives with Broad-Spectrum Bacteriostatic Antibacterial Properties

Molecules, Journal Year: 2023, Volume and Issue: 28(21), P. 7357 - 7357

Published: Oct. 31, 2023

This study investigated the potential of clindamycin derivatives with broad-spectrum antibacterial properties. The main goal was to identify new targets lay foundation for developing novel antimicrobial agents. research used molecular docking and dynamics simulations explore how could combat bacterial resistance widen their capabilities. Three different were studied against 300 target proteins. Among these, 26 proteins found be common all three derivatives. After further screening through simulations, four specific protein identified. Notably, one these targets, cell division FtsZ, primarily located in cyto cyto_nucl compartments. These findings suggest that have address broaden effectiveness identified targets.

Language: Английский

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Elucidating the protective mechanism of ganoderic acid DM on breast cancer based on network pharmacology and in vitro experimental validation

Biotechnology and Applied Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

Abstract Ganoderma lucidum , a popular medicinal fungus, has been utilized to treat variety of diseases. It possesses unique therapeutic and pharmacological reputation in suppressing cancer/tumor progression, especially breast cancer, due its embedded rich bioactive chemical constituents, mainly triterpenoids (ganoderic acids). The most prevalent malignant tumor women with high mortality morbidity rate is cancer. Ganoderic acids A, D, DM, F, H are evidenced previous research have cancer–preventive properties by exhibiting autophagic apoptosis, anti‐proliferative, anti‐angiogenesis effects. However, the anti‐breast cancer mechanism remains unclear. putative targets ganoderic were further determined using bioinformatics techniques molecular docking calculation. Finally, key verified vitro. A total 53 potential target proteins associated 202 pathways predicted be related narrowed down six (AKT1, PIK3CA, epidermal growth factor receptor [EGFR], STAT1, ESR1, CTNNB1), different algorithms CytoHubba plugin, which validated analysis. acid DM (GADM) (PIK3CA EGFR) strongest interactions via MDA‐MB‐231 MCF7 cells. expression level PIK3CA both cells was dose‐dependently suppressed GADM, whereas EGFR unexpectedly increased, warrants investigation. These data indicated that network pharmacology–based prediction GADM for treating human could reliable.

Language: Английский

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Potential Targets and Signaling Mechanisms of Cinnamaldehyde Enhancing Intestinal Function and Nutritional Regulation in Fat Greenling (Hexagrammos otakii)

Aquaculture Nutrition, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

Cinnamaldehyde is an ideal feed additive with good immune enhancement and anti‐inflammatory regulation effects. However, the mechanism in fat greenling ( Hexagrammos otakii , H. ) remains unclear. The nine targets of cinnamaldehyde were gathered identified by Traditional Chinese Medicine Systems Pharmacology database Uniprot database, 1,320 intestinal inflammation disease (IIF)‐related proteins screened from DrugBank, Online Mendelian Inheritance Man (OMIM), Genecards, Pharmacogenetics Pharmacogenomics Knowledge Base (PHARMGKB) Databases. According to Gene Ontology enrichment results Kyoto Encyclopedia Genes Genomes pathway results, may regulated responses bacteria, lipopolysaccharide, inflammatory cytokine, external stimuli via nuclear factor kappa‐B (NF κ B) signaling within on network. In addition, protein–protein interaction analysis assisted obtaining closely related regulatory proteins, including C5a anaphylatoxin chemotactic receptor 1 (C5aR1), transcription p65 (RELA), prostaglandin G/H synthase 2 (PTGS2), toll‐like 4 (TLR4), which confirmed as bottleneck nodes network be more deeply verified molecular docking. Moreover, a feeding model was established for evaluating effect vivo . current findings implied that play protective role against IIF reducing through C5 complement (C5)/C5aR1/interleukin‐6 (IL‐6) TLR4/NF B/PTGS2 pathway. study focused investigating action combining pharmacology experimental verification provided fresh perspective promoting fish.

Language: Английский

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Napthyridine-derived compounds as promising inhibitors for Staphylococcus aureus CrtM: a primer for the discovery of potential anti-Staphylococcus aureus agents

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 24, 2023

The disease-free existence of humans is constantly under attack by a variety infections caused organisms including bacteria. Notable among the bacteria Staphylococcus aureus which an etiological organism for impetigo, folliculitis, and furuncles. response human immune system against this disease often neutralized production pigment called Staphyloxanthin (STX) via series reactions mediated several enzymes. Among these enzymes, dehydrosqualene synthase, also known as CrtM, has emerged viable drug target due to its role in mediating first step pathway. Consequently, study employs molecular modeling approaches docking, quantum mechanical calculations, dynamics (MD) simulations others investigate potential napthyridine derivatives serve inhibitors CrtM. results revealed high binding affinities compounds demonstrated their docking scores, while further subjection screening pipeline aimed at determining fitness development into drugs just one compound namely 6-[[1-[(2-fluorophenyl) methyl]triazol-4-yl]methoxy]-4-oxo-1H-1,5-naphthyridine-3-carboxylic acid with good drug-like, pharmacokinetics, toxicity properties profiles. A 100 ns-long MD simulation complexes formed after stable interaction target. Ultimately, can be promising outlet discover weapon fight clinically resistant bacteria, however, experimental studies are suggested carry out wet lab, pre-clinical, clinical levels.

Language: Английский

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Clindamycin Derivatives: Unveiling New Prospects as Potential Anti-Tumor Agents

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 19, 2024

Abstract This study investigates the anti-tumor potential of Clindamycin derivatives, compounds 3 and 3e, through a multidisciplinary approach. Screening 200 Clindamycin-associated targets identified Family A G-protein-coupled receptor as prominent target. Subsequent analyses revealed 16 relevant proteins, with compound demonstrating strong association specific protein via stable hydrogen bonding. Molecular dynamics simulations adrenergic β critical target, predominantly localized in plasma membrane endoplasmic reticulum. These findings suggest that may enhance natural defense mechanisms against tumors by regulating immune responses tumor microenvironment, offering avenue for novel drug development.

Language: Английский

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FMS-like tyrosine kinase 3 inhibitory potentials of some phytochemicals from anti-leukemic plants using computational chemical methodologies

Open Chemistry, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 1, 2024

Abstract Acute myeloid leukemia (AML) takes center stage as a highly prevalent and aggressive clonal disorder affecting hematological stem cells. FMS-like tyrosine kinase 3 (FLT3) mutations were in nearly 30% of the AML cases. However, efforts have led to development anti-mutant FLT3 drugs, such midostaurin, gilteritinib, quizartinib, improve treatments. Currently, we are exploring ability compounds from anti-leukemic plants be used therapies, focusing on mutant inhibition. Employing computational techniques drug-likeness assessment, molecular docking, pharmacokinetics properties profiling, dynamics simulations (MDS), free energy calculations, identified 43 out 57 with oral drug potential. Notably, 7 compounds, including flavopiridol, sanggenol Q, norwogonin, oblongixanthones A, B, apigenin, luteolin exhibited strong binding affinities ranging −9.0 −9.8 kcal/mol, surpassing control gilteritinib (−6.3 kcal/mol). flavopiridol norwogonin displayed favorable low toxicity profiles. MDS confirmed stability their through parameters root mean square deviation, fluctuation, radius gyration ( R g ) over 100 ns simulations. Flavopiridol emerge promising candidates for inhibitors. Therefore, experimental studies warranted validate therapeutic

Language: Английский

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