Virtual perspectives of sanguinarine on cancer prevention and treatment through molecular dynamic study

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 25, 2025

Language: Английский

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Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals using in silico prospective screening approaches

Saudi Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 31(5), P. 103977 - 103977

Published: March 11, 2024

Atherosclerosis is potentially correlated with several cardiac disorders that are greatly associated cellular oxidative stress generation, inflammation, endothelial cells dysfunction, and many cardiovascular complications. Berberine a natural isoquinoline alkaloid compound widely modulates pathogenesis of atherosclerosis through its different curative potentials. This in silico screening study was designed to confirm the potent restorative properties berberine chloride as multitarget-mediated against CVDs their complications screening, identifying, visualizing, evaluating binding models, affinities, interactions toward CVDs-related targets direct and/or indirect-mediated signals via inhibiting ER apoptotic activating autophagy pathway. The drug-likeness were predicted using computational QSAR/ADMET Lipinski's RO5 analyses well molecular docking simulations. berberine-binding modes, residues-interaction patterns, free energies scores towards estimated tools. Furthermore, pharmacokinetic toxicological features clearly determined. According this virtual study, could restore function improve pathogenic atherosclerotic alleviating signals, autophagy, improving insulin sensitivity, decreasing hyperglycemia dyslipidemia, increasing intracellular RCT signaling, attenuating vascular upregulating antioxidant defenses tissues. In modulated targets, including SIGMAR1, GRP78, CASP3, BECN1, PIK3C3, SQSTM1/p62, LC3B, GLUT3, INSR, LDLR, LXRα, PPARγ, IL1β, IFNγ, iNOS, COX-2, MCP-1, IL10, GPx1, SOD3.

Language: Английский

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Molecular interactions between metformin and D-limonene inhibit proliferation and promote apoptosis in breast and liver cancer cells

BMC Complementary Medicine and Therapies, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 6, 2024

Abstract Background Cancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action agents imperative. Hypothesis/Purpose In this study, we evaluated utility metformin D -limonene, alone or in combination, as potential therapeutics using human liver breast cancer cell lines HepG2 MCF-7. Study design An integrated systems pharmacology approach presented for illustrating molecular interactions between -limonene. Methods We applied systems-based analysis to introduce drug–target–pathway network clarifies different mechanisms treatment. The combination treatment -limonene induced apoptosis both compared with single drug treatments, indicated by flow cytometric gene expression analysis. Results mRNA Bax P53 genes were significantly upregulated while Bcl-2 , iNOS, Cox-2 downregulated all groups normal cells. percentages late apoptotic MCF-7 cells higher groups, particularly group. Calculations index (CI) revealed synergistic effect drugs (CI = 0.14) 0.22). Conclusion Our data show metformin, their combinations exerted significant antitumor effects on inducing modulating genes.

Language: Английский

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Medical and Biological Role of Apigenin: A Comprehensive Review

Pharmacological Research - Modern Chinese Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100576 - 100576

Published: Jan. 1, 2025

Language: Английский

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Phytochemical and antibacterial properties of calyces Hibiscus sabdariffa L.: an in vitro and in silico multitarget-mediated antibacterial study

BMC Complementary Medicine and Therapies, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 18, 2025

Abstract Background Multidrug-resistant (MDR) bacteria pose a significant threat to human health worldwide by increasing the harmful impact of traditional synthetic antibiotics. Traditional medicinal plants have bioactive metabolites that can significantly modulate growth rate, cell survival, and pathogenicity antibiotic-resistant bacteria. Hibiscus sabdariffa L., known as Roselle or Karkade, belongs Malvaceae family. It is well-known for its edible aromatic red/purple calyces extensively utilized in food industry pharmacological applications. H. calyx phytocompounds potent therapeutic activities such antimicrobial, antidiabetic, antiobesity, antioxidant, anti-inflammatory, anticancer properties. Methods This study gas chromatography-mass spectrometry (GC-MS) analysis determine volatile compounds found hydroethanolic extract calyces. The purpose was verify antibacterial properties against selective MDR clinical bacterial isolates, including A. baumanii , E. coli K. pneumoniae P. aeruginosa . Results GC-MS spectrum profile revealed presence twenty-seven organic components, fatty acid derivatives, ester compounds, sugar terpene components. major fractionations main active chemical compositions flowers were ( E )-10-Octadecenoic methyl (59.23%), 8,11-Octadecadienoic acid, (11.51%), Butanedioic 3-hydroxy-2,2-dimethyl-, diethyl (6.22%), Diethyl succinate/Butanedioic (2.35%), Heptadecanoic 16-methyl-, ester/Methyl isostearate (2.31%). dried demonstrated (zones diameter inhibition growth, MIC, MBC, MBC/MIC) determined phytochemical screening (TAC, TFC, TPC) antioxidant activity (DPPH). surface morphological characteristics treated isolates been affected comparison untreated forms calyces, scanning electron microscopy (SEM). In silico predictive investigation components exhibited scoring functions, binding affinities, non-covalent intermolecular interactions with MenB lyase DNA gyrase targets These enhanced pathogenicity, differentiation isolates. Conclusions According vitro findings, has shown potentials an effective treatment. contains Gram-negative

Language: Английский

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Exploring The Molecular Impact of Achillea arabica on Hepatocellular Carcinoma: A Computational Study

Journal of Computational Biophysics and Chemistry, Journal Year: 2025, Volume and Issue: 24(07), P. 909 - 931

Published: Jan. 9, 2025

Hepatocellular carcinoma, presenting a significant health challenge, requires innovative approaches for treatment and prevention. Therefore, this study aimed to comprehensively characterize the potential of compounds from Achillea arabica on mTOR, Akt ERK signaling pathways using in silico methods. The drug likeness ADME/T properties were investigated online tools. Molecular docking molecular dynamics simulations used examine key interactions selected with target proteins along known inhibitors. Three phenolic demonstrated strong binding affinity as top candidates. Compounds quercetin, luteolin apigenin exhibit nontoxic alternatives hepatocellular carcinoma treatment, typically synthetic chemical

Language: Английский

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Phytochemical baicalin potentially inhibits Bcl-2 and VEGF: an in silico approach

Frontiers in Bioinformatics, Journal Year: 2025, Volume and Issue: 5

Published: Feb. 19, 2025

The rising prevalence of cancer cells exhibits uncontrolled growth and invasive aggressive properties, leading to metastasis, which poses a significant challenge for global health. Central development are proteins such as NF-kB, p53, VEGF, BAX/Bcl-2, play important roles in angiogenesis, cell apoptosis regulation, tumor growth. This silico study evaluates the activity six different natural well novel therapeutic strategies against cancer. Using computational approach, i.e., virtual screening, molecular docking, dynamics (MD) simulations, binding affinities interactions selected phytochemicals with cancer-specific were analyzed. Key criteria selection included affinity, stability, pharmacokinetic toxicological properties. Post-selection, ligand-protein further examined through MD simulations conducted using Desmond-Maestro 2020-4 on Linux-based HP Z2 workstation, providing an insight into conformational changes stability inhibitor-protein complexes. was complemented by ADMET predictions assess pharmacokinetics profiles. Our findings reveal that out phytochemicals, baicalin exhibited most promising results, docking scores -9.2 kcal/mol -9.0 Bcl-2 VEGF receptors, respectively. simulation (100 ns) confirmed baicalin-protein interactions, supported hydrophobic intermolecular hydrogen bonds. RMSD RMSF values exhibit acceptable minimum (3.5-6 Å) BAX/Bcl-2. highlights potential baicalin, phytochemical known anti-cancerous, anti-apoptotic, anti-proliferative candidate treatment. Further exploration validation its inhibitory mechanisms could open avenue approaches oncology.

Language: Английский

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Network pharmacology and in vivo evidence of the pharmacological mechanism of geniposide in the treatment of atherosclerosis

BMC Complementary Medicine and Therapies, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 24, 2024

Abstract Background Atherosclerosis (AS) is a fundamental pathological state in various cardiovascular diseases. Geniposide, which the main active component of Gardenia jasminides , effective against AS. However, underlying molecular mechanisms remain unclear. Here, we sought to elucidate them. Methods The targets AS and geniposide were collected from online public databases. potential mechanism Geniposide treating was predicted by constructing protein–protein interaction (PPI) network conducting Gene Ontology (GO) Kyoto Encyclopaedia Genes Genomes (KEGG) pathway enrichment analyses. Hub proteins core pathways verified docking vivo experiments. Moreover, effect on assessed measuring atherosclerotic plaque area thoracic aorta mice. ApoE −/− mice used establish models randomly divided into different groups. Two doses administered Hematoxylin eosin (HE) staining performed evaluate effects Oil Red O Sirius stability. protein expression key markers involved signalling examined using western blotting immunofluorescence. Results A total 239 targets, 3418 AS-related disease 129 overlapping identified. genes detected, revealed that strongly interacted with hub (AKT1, VEGFA, CTNNB1, MMP9, EGFR). 109 pathways, including Rap1 pathway, identified analysis. results experiments demonstrated reduced body weight blood lipid levels, alleviated formation plaques, enhanced stability, inhibited inflammation, at least partially, activating Rap1/PI3K/Akt Conclusion can alleviate enhance stability plaques regulating pathway.

Language: Английский

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Integrating Computational Methods in Network Pharmacology and In Silico Screening to Uncover Multi-targeting Phytochemicals against Aberrant Protein Glycosylation in Lung Cancer

ACS Omega, Journal Year: 2023, Volume and Issue: 8(23), P. 20303 - 20312

Published: May 30, 2023

Glycoproteins are an underexploited drug target for cancer therapeutics. In this work, we integrated computational methods in network pharmacology and silico docking approaches to identify phytochemical compounds that could potentially interact with several cancer-associated glycoproteins. We first created a database of phytochemicals from selected plant species, Manilkara zapota (sapodilla/chico), Mangifera indica (mango), Annona muricata (soursop/guyabano), Artocarpus heterophyllus (jackfruit/langka), Lansium domesticum (langsat/lanzones), Antidesma bunius (bignay), performed pharmacokinetic analysis determine their drug-likeness properties. then constructed phytochemical-glycoprotein interaction characterized the degree interactions between glycoproteins other glycosylation-related proteins. found high α-pinene (Mangifera indica), cyanomaclurin (Artocarpus heterophyllus), genistein (Annona muricata), kaempferol bunius), norartocarpetin quercetin muricata, bunius, zapota, rutin domesticum), ellagic acid (Antidesma indica). Subsequent confirmed these bind EGFR, AKT1, KDR, MMP2, MMP9, ERBB2, IGF1R, MTOR, HRAS proteins, which known biomarkers. vitro cytotoxicity assays extracts showed n-hexane, ethyl acetate, methanol leaf A. L. M. gave highest growth inhibitory activity against A549 lung cells. These may help further explain reported cytotoxic activities select species.

Language: Английский

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Insights into the dynamic interactions of RNase a and osmolytes through computational approaches

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(11), P. 5903 - 5911

Published: June 26, 2023

Osmolytes are small organic molecules that known to stabilize proteins and other biological macromolecules under various stressful conditions. They belong categories such as amino acids, methylamines, polyols. These substances commonly 'compatible solutes' because they do not disrupt cellular processes help regulate the osmotic balance within cells. In case of ribonuclease A (RNase A), which is prone aggregation, presence osmolytes can maintain its structural stability prevent unwanted interactions leading protein aggregation. this study, we investigated interaction between RNase several using molecular docking dynamics (MD) simulations. We performed predict binding mode affinity each osmolyte with A. MD simulations were then carried out investigate A-osmolyte complexes. Our results show two osmolytes, glucosylglycerol sucrose have favorable affinities The possible role these in stabilizing prevention aggregation also explored. By providing computational insights into study offers valuable information could aid comprehending mechanisms by protect designing therapeutics for protein-related disorders based on osmolytes. findings may significant implications development novel strategies aimed at preventing misfolding diverse disease conditions.Communicated Ramaswamy H. Sarma

Language: Английский

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