Integrated bioinformatics, network pharmacology, molecular docking, and molecular dynamics simulation to explore the potential pharmacological mechanism of Erigeron breviscapus (Vant.) Hand-Mazz regulating ferroptosis for the treatment of Alzheimer's disease

Journal of Molecular Structure, Год журнала: 2024, Номер 1314, С. 138698 - 138698

Опубликована: Май 21, 2024

Ferroptosis plays a role in Alzheimer's disease (AD) development. Erigeron breviscapus (Vant.) Hand-Mazz (EBHM) shows promising effects treating cognitive impairment-related diseases. However, the mechanisms by which EBHM regulates ferroptosis AD treatment are not fully understood. This study used bioinformatics, network pharmacology, molecular docking, and dynamics simulation to explore how treatment. The results identified four key genes—HSPA8, GSK3B, CTSB, YWHAG—that involved this regulation, constructed multigene diagnostic model for AD. demonstrated moderate accuracy (area under curve [AUC] = 0.636) distinguishing from non-demented (ND) was further validated with external datasets showing good capabilities (AUC values of 0.898, 0.889, 0.746, 0.712). Additionally, CIBERSORT analysis revealed significant correlation between immune cell infiltration these genes, highlighting their potential immunity. Molecular docking studies indicated that 3,4,5-tricaffeoylquinic acid (TCQA) had highest binding affinity HSPA8, suggesting TCQA HSPA8 components core targets EBHM's regulation therapy. simulations confirmed stability strong TCQA-HSPA8 complex. These findings enhance our understanding underlying may offer new avenues developing effective treatments.

Язык: Английский

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Target-centric analysis of hepatitis B: identifying key molecules and pathways for treatment

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 6, 2024

Hepatitis B virus (HBV) poses a significant global health challenge, potentially leading to severe liver conditions, with currently limited effective treatment options available. Xiao-Chai-Hu-Tang (XCHT), well-known Traditional Chinese Medicine (TCM) prescription, shows promise in clinical trials for treating HBV. Therefore, screening the complex components of XCHT, identifying active compounds, and closely exploring targets associated hepatitis may constitute an strategy development new therapeutic drugs this disease. A systematic pharmacology GEO chip analysis identified key pathways ingredients. Molecular docking molecular dynamics simulation techniques were used explore affinity stability compounds core targets, while assessing druggability safety compounds. The effect compound protoporphyrin XCHT on mediated through such as AKT1, MAPK1, LCK, well signaling like PI3K-Akt pathway Ras pathway. Protoporphyrin effectively bond pockets demonstrated favorable high threshold. study provided valuable insights into treatments B.

Язык: Английский

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FT-IR Analysis and Acute Toxicity of the Extracts of Wild-Growing Saussurea sordida, Saussurea alpina Native to Kazakhstan

Опубликована: Фев. 29, 2024

Natural products from medicinal plants, either as pure compounds or standardized extracts, provide unlimited opportunities for new drug leads because of the unmatched availability chemical diversity. The objects study are plant raw materials Saussurea sordida Kar&Kir and alpina DC. collected South Kazakhstan during flowering period in spring-summer months 2021. present was aimed to investigate toxic effects acute administration ethanol extracts plants S. male Wistar rats. extract by subjected Phytochemical Screening, Fourier transform infrared spec-troscopy (FTIR) analysis. screening revealed presence phenolic compounds. FT-IR spectroscopic analysis various characteristic band values with functional groups formulation such amines, alcohol, phenol, alkane, alkene, conjugated acid groups. peak alcohols, phenols, carboxylic acids, aldehydes, amides, amino anhydrides, esters, ketones, unsaturated aliphatic, aromatics, heterocycles, nitro compound, alkanes, al-kenes sugars. Histological examination organ samples after studying chronic toxicity ex-tracts two species (S. . alpina) no pathological changes. lethal behavioral signs at tested doses indicating that LD50 is greater than 2000 mg/kg. These results show low on short-term use liver long-term use. This helps predict formula structure active molecules which can be used drugs. result also enhances traditional usage , possesses a number bioactive

Язык: Английский

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Zangsiwei prevents particulate matter-induced lung inflammation and fibrosis by inhibiting the TGF-β/SMAD pathway

Journal of Ethnopharmacology, Год журнала: 2024, Номер 337, С. 118752 - 118752

Опубликована: Сен. 2, 2024

Zangsiwei(ZSW) is a traditional Tibetan medicine from China consisting of extracts Rhododendron anthopogonoides Maxim, Gentiana Tourn, Corydalis hendersonii Hemsl and Berberis kansuensis C.K.Schneid. Traditionally, ZSW has been used by physicians to treat chronic respiratory diseases. The role in particulate matter-induced lung inflammation fibrosis remains unclear.

Язык: Английский

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Sanguinarine identified as a natural dual inhibitor of AURKA and CDK2 through network pharmacology and bioinformatics approaches

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Ноя. 28, 2024

Cervical cancer (CA) continues to be a female malignant tumor with limited therapeutic options, resulting in high mortality rate. Sanguinarine (SANG), naturally occurring alkaloid, has demonstrated notable efficacy preclinical treatment of CA. However, the mechanism through which SANG acts against CA is not fully understood. To address this, utilizing nine drug target prediction databases, we have successfully identified 379 potential targets for SANG. Venn diagram analysis compared 2367 CA-related from GeneCards disease database, 2618 CA-closely related derived multiple datasets GEO WGCNA analysis, and SANG, 35 shared targets. Subsequently, by employing PPI network Cytohubba plugin, Human Protein Atlas, TCGA database data, ROC curve AURKA CDK2 as key combating Single-gene GSEA results suggest that overexpression closely correlated DNA replication, cell cycle progression, various repair pathways Molecular docking molecular simulation dynamics analyses confirmed stable binding both In summary, integrating diverse methodological approaches, this study discovered potentially inhibits features targeting CDK2, thereby regulating pathways. This lays solid foundation further exploring pharmacological role therapy. in-depth vitro vivo experiments are required corroborate our findings.

Язык: Английский

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Network pharmacology and experimental evaluation strategies to decipher the underlying pharmacological mechanism of Traditional Chinese Medicine CFF-1 against prostate cancer

Aging, Год журнала: 2024, Номер 16(6), С. 5387 - 5411

Опубликована: Март 13, 2024

Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 clinical treatments for PCa several years. Here, we aimed to identify the underlying mechanism of on using network pharmacology and experimental validation. Active ingredients, potential targets were acquired from public databases. Subsequently, protein-protein interaction (PPI) herbs-active ingredients-target was constructed. A prognostic model also constructed based key targets. In vitro experiments cell lines CWR22Rv1 PC-3 carried out validate PCa. total 112 bioactive compounds 359 screened PPI analysis determined 12 genes as main Molecular docking studies indicated that primary active ingredients possess strong binding affinity top five hub DNMT3B, RXRB HPRT1 found be involved immune regulation vitro, inhibit proliferation, migration, invasion induce apoptosis via PI3K-Akt, HIF-1, TNF, EGFR-TKI resistance PD-1 checkpoint signaling pathways. This study comprehensively elucidates molecular against PCa, offering rationale application treatment.

Язык: Английский

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Identification and analysis of co-disease genes between COVID-19 and osteoarthritis

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 11, 2024

Abstract Background: The molecular mechanisms of corona virus disease 2019 (COVID-19) and osteoarthritis (OA) are unclear, there is an urgent need to identify new biomarkers explore their potential in COVID-19 OA . Methods : GSE57218, GSE157103 training sets the GSE82107, GSE171110 validation were acquired via gene expression omnibus (GEO) database. First, differentially expressed genes (DEGs) between normal samples GSE57218 respectively sifted out by differential analysis. modules with highest correlation normal, non gained weighted co-expression network analysis (WGCNA), individually. Then, OA-DEGs intersected module that had significant OA, COVID-19-DEGs which dramatically correlated yield OA-intersected genes, respectively. candidate they analyzed for function enrichment Next, seven algorithms (Closeness, MCC, Degree, MNC, Radality, Stress EPC) performed on sift biomarkers. Finally, we constructed competing endogenous RNA (ceRNA), transcription factor (TF)/miRNA-mRNA drug-target regulatory networks. Results: There 1135 4336 sets, pink, blue brown correlations set, while pink notably COVID-19. We finally 715 2282 COVID-19-intersected genes. After intersecting above two 106 involved ADP metabolic process, nucleoside diphosphate phosphorylation, etc.. 7 biomarkers, namely AK1, APP, ENO1, TPI1, HSP90B1, HSPB1 ESR1, based algorithms. successfully ceRNA, TF/miRNA-mRNA Conclusion Through bioinformatic methods, explored (AK1, ESR1) combined providing ideas studies related treatment comorbidity.

Язык: Английский

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Revealing the role of metformin in gastric intestinal metaplasia treatment

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 19, 2024

Objective Gastric intestinal metaplasia (IM) is a precancerous stage associated with gastric cancer. Despite the observed beneficial effects of metformin on IM, its molecular mechanism remains not fully elucidated. This study aims to reveal and potential mechanisms in treating IM based both bioinformatics vivo investigations. Methods The seven public databases (GeneCards, DisGeNET, OMIM, SuperPred, Pharm Mapper, Swiss Target Prediction, TargetNet) were used this work identify targeted genes related metformin. shared between further analyzed by network pharmacology, while interactions in-between investigated docking. In parallel, therapeutic effect was evaluated mice model, core targets pathways effected verified . Results We screened out 1,751 IM-related 318 metformin-targeted genes, 99 common identified visualized constructing protein-protein interaction (PPI) network. top ten EGFR , MMP9 HIF1A HSP90AA1 SIRT1 IL2 MAPK8 STAT1 PIK3CA ICAM1 functional enrichment analysis confirmed that carcinogenesis HIF-1 signaling primarily involved treatment IM. Based docking dynamics, we found affected function inhibiting receptor binding. Furthermore, administration reduced progression lesions Atp4a −/− model significantly. Notably, enhanced expression level MUC5AC inhibited CDX2 Our results also showed modulated reducing activity NF-κB PI3K/AKT/mTOR/HIF-1α pathway. Conclusion confirms improves efficacy regulating complex Metformin plays role inflammation/apoptosis-related progression. provides foundation for understanding other guanidine medicines treatment.

Язык: Английский

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Unraveling the relevance of SARS-Cov-2 infection and ferroptosis within the heart of COVID-19 patients

Heliyon, Год журнала: 2024, Номер 10(17), С. e36567 - e36567

Опубликована: Авг. 24, 2024

The coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome 2 (SARS-CoV-2), which led to a huge mortality rate and imposed significant costs on the health system, causing damage cells of different organs such as heart. However, exact details mechanisms behind this are not clarified. Therefore, we aimed identify cell molecular mechanism heart SARS-Cov-2 infection.

Язык: Английский

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Pharmacoinformatic screening of phytoconstituent and evaluation of its anti-PDAC effect using in vitro studies

Journal of Biomolecular Structure and Dynamics, Год журнала: 2022, Номер 41(20), С. 10627 - 10641

Опубликована: Дек. 12, 2022

With no prominent treatment for pancreatic ductal adenocarcinoma (PDAC) in conventional chemotherapy, recent studies have focused on uniting and traditional medicines including plant phytoconstituents. Herein, we used pharmacoinformatic to identify potent phytoconstituent as ligand having inhibition activities against canonical anticancer targets, evaluated its effect PDAC cell lines. SwissTargetPrediction SuperPred tools were utilized segregate protein targets of humans, following which FunRich was applied garner PDAC. STRING analysis predicted protein–protein interactions dynamic simulation confirmed stability ligand–protein complex. For vitro cytotoxic potential, at different concentrations given lines both alone combined with gemcitabine, followed by evaluation effects migration. Differential gene expression checked using PCR evaluating mechanism cytotoxicity. Results showed pentagalloylglucose (PGG) highest docking MMGBSA scores Cyclooxygenase 2 (Cox2) site. detected 40 PGG Simulation data protein–ligand In experiments Mia-PaCa-2 more sensitive than Panc-1. successfully inhibited migration combination gemcitabine. Additionally, induced apoptosis the lines; but antagonism when conclusion, our report demonstrates has good binding Cox2 anti-PDAC activity inhibiting inducing apoptosis, thus it can be a therapy option. But further are required confirm behaviour drug.Communicated Ramaswamy H. Sarma

Язык: Английский

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