Search Results (2,603)

Treatment for acute liver failure (ALF) is constrained by shortages of liver transplant donors and immune rejection. Porcine bone marrow mesenchymal stem cells (pBMSCs) demonstrate clinical potential in xenotransplantation due to their abundant availability, low immunogenicity, and strong proliferative activity. This study is the first to investigate the reparative effects and mechanisms of pBMSCs derived from Luopan Mountain pigs in a D-galactosamine (D-GalN)-induced ALF rat model. The results demonstrated that tail-vein transplantation of pBMSCs significantly improved survival rates in ALF rats; reduced serum ALT, AST, and TBIL levels; enhanced hepatic glycogen metabolism; and mitigated histopathological liver damage. Additionally, pBMSC transplantation upregulated serum HGF, IGF-1, and VEGF levels while inhibiting hepatocyte apoptosis. Mechanistic studies indicate that pBMSCs promote liver function recovery and regeneration by activating the PI3K/Akt/mTOR signaling pathway and suppressing its key negative regulator, PTEN, by regulating the expression of key genes involved in inflammation, fibrosis, proliferation, and apoptosis. This study provides crucial experimental evidence for the use of pBMSCs in treating acute liver failure (ALF) and lays the groundwork for its clinical translation in the field of xenotransplantation. Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major causes of morbidity and mortality, yet no targeted pharmacological therapy is available. Excessive neutrophil and macrophage infiltration drives reactive oxygen species (ROS) production and cytokine release, leading to alveolar–capillary barrier disruption and fatal respiratory failure. Methods: We applied an integrative multi-omics strategy combining single-cell transcriptomics, peripheral blood proteomics, and lung tissue proteomics in a lipopolysaccharide (LPS, 10 mg/kg)-induced mouse ALI model to identify key signaling pathways. Harpagide, an iridoid glycoside identified from our natural compound screen, was evaluated in vivo (40 and 80 mg/kg) and in vitro (0.1–1 mg/mL). Histopathology, oxidative stress markers (SOD, GSH, and MDA), cytokine levels (IL-6 and IL-1β), and signaling proteins (HIF-1α, p-PI3K, p-AKT, Nrf2, and HO-1) were quantitatively assessed. Direct target engagement was probed using surface plasmon resonance (SPR), the cellular thermal shift assay (CETSA), and 100 ns molecular dynamics (MD) simulations. Results: Multi-omics profiling revealed robust activation of HIF-1, PI3K/AKT, and glutathione-metabolism pathways following the LPS challenge, with HIF-1α, VEGFA, and AKT as core regulators. Harpagide treatment significantly reduced lung injury scores by ~45% (p < 0.01), collagen deposition by ~50%, and ROS accumulation by >60% relative to LPS (n = 6). The pro-inflammatory cytokines IL-6 and IL-1β were reduced by 55–70% at the protein level (p < 0.01). Harpagide dose-dependently suppressed HIF-1α and p-AKT expression while enhancing Nrf2 and HO-1 levels (p < 0.05). SPR confirmed direct binding of Harpagide to HIF-1α (KD = 8.73 µM), and the CETSA demonstrated enhanced thermal stability of HIF-1α. MD simulations revealed a stable binding conformation within the inhibitory/C-TAD region after 50 ns. Conclusions: This study reveals convergent immune–microenvironmental regulatory mechanisms across cellular and tissue levels in ALI and demonstrates the protective effects of Harpagide through multi-pathway modulation. These findings offer new insights into the pathogenesis of ALI and support the development of “one-drug, multilayer co-regulation” strategies for systemic inflammatory diseases. Full article

Background/Objectives: Prenatal exposure to famine can lead to lasting health effects through changes in DNA methylation. This study aims to evaluate the impact of prenatal exposure to the Chinses Great Famine (1959–1961) on human epigenome and the subsequent influence on blood lipids. Methods: We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and prenatal exposure to the Chinese Great Famine as well as blood lipids among eight participants exposed to famine and eight sex-matched participants (born ≤ 3 years after the famine). Genome-wide DNA methylation sites were profiled using the Illumina EPIC BeadChip, which covers 850K methylation positions. Results: After EWAS analyses, seven probes in genes C8orf31, ELAVL1, U6, GBA2, SHOX2, SLC1A4, and NPHP4 reached p < 1 × 10⁻⁵. Of these, famine exposure was associated with decreased methylation levels of a GBA2 exonic probe cg08258661 (p = 4.9 × 10⁻⁶). After false discovery rate (FDR) correction, pathway enrichment analyses for genes harboring nominally significant (p < 0.05) probes identified 44 significant pathways (q < 0.05), and 5 pathways were related to lipid metabolism. After FDR correction in each pathway, probes cg02622866 (5’UTR of ATF2, p = 1.09 × 10⁻³), cg07316730 (body of GRB2, p = 1.32 × 10⁻³), and cg01105385 (body of PIK3R1, p = 1.94 × 10⁻³) in the PI2K-Akt signaling pathway were associated with blood LDL-C (q ≤ 0.04); probes cg09180702 (3’UTR of PIGQ, p = 9.21 × 10⁻⁵, and q = 0.04) and cg01421548 (body of HS3ST4, p = 5.23 × 10⁻⁵, and q = 0.01) in the metabolism pathway were associated with blood LDL-C and HDL-C, respectively; In addition, probe cg08460387 (5’UTR of MAN1C1, p = 1.09 × 10⁻⁴, and q = 0.02) in the vesicle-mediated transport pathway was associated with log-transformed blood triglycerides. Conclusions: Through an epigenetic study of the Chinese Great Famine, we identified six novel genes involved in lipid metabolism. Full article

Accumulating evidence indicates that bisphenol A (BPA) analogs, including bisphenol B (BPB) and bisphenol S (BPS), disrupt testicular function and contribute to male reproductive dysfunction (MRD). However, whether BPA analogs are involved in MRD among middle-aged men remains inconclusive. Therefore, we selected cryptorchidism, erectile dysfunction, premature ejaculation, and testicular tumors as representative MRD conditions in middle-aged individuals, aiming to explore the molecular mechanisms that may be disrupted by bisphenols (BPs). By using GeneCards, STRING and Cytoscape, TP53, AKT1, and MYC were pinpointed as core targets associated with MRD. Enrichment analysis suggested that BPs may induce MRD by disrupting steroidogenesis. UPLC-MS/MS analysis showed that both BPB and BPS exhibit specific accumulation in the testes. Following 20-day exposure to 0.3 or 0.6 mg/kg body weight/day BPB or BPS, testosterone levels and the expression of hub genes were decreased. The molecular docking results demonstrated that both BPB and BPS can directly bind to members of the cytochrome P450 family, potentially interfering with sex hormone biosynthesis. Our study identified the targets and mechanisms through which BPB and BPS induce MRD in middle-aged males, thereby providing insights for the safety assessment of BPs. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by social/communication deficits and behavioral abnormalities, with neuronal apoptosis and immune-inflammatory dysregulation implicated in its pathogenesis. Marine-derived polysaccharides, particularly those from Enteromorpha prolifera (PEPs), exhibit neuroprotective and anti-inflammatory properties—yet their therapeutic potential for ASD remains unexplored. Major monosaccharide components of PEPs were identified as rhamnose, xylose, glucose, glucuronic acid, galactose, and ribose through ion chromatography analysis. Infrared spectroscopy confirmed PEPs as pyranose-type polysaccharides with α-glycosidic bonds and uronic acids, while gel permeation chromatography showed a predominant molecular weight of 3.813 kDa (83.919%). To explore the therapeutic potential of PEPs in ASD, a comprehensive method combining network pharmacology, molecular docking, and in vitro validation was conducted. A total of 235 ASD-related target proteins were predicted, with enrichment analyses indicating significant involvement in pathways such as neuroactive ligand–receptor interaction and the MAPK signaling pathway. In vitro assays using valproic acid (VPA)-induced HT22 neuronal cells showed that PEPs significantly attenuated apoptosis. Western blot analysis further confirmed the downregulation of HSP90AA1, cleaved CASP3/pro-CASP3, p-NF-κB1/NF-κB1, p-AKT1/AKT, and p-mTOR/mTOR, as well as the upregulation of IκBα after PEPs treatment. These findings suggest that PEPs exert neuroprotective effects through the modulation of apoptosis and inflammation-related signaling pathways, supporting their potential as a promising candidate for further study in ASD. Full article

This study aimed to evaluate the effects of fermented blueberry pomace (FBP) supplementation on carcass traits, meat quality, and antioxidant capacity in spent hens and further investigated underlying mechanisms using network pharmacology and molecular docking analyses. A total of 320 Yukou Jingfen No. 8 spent hens (345 days old) were fed a basal diet supplemented with 0, 0.25, 0.5, or 1.0% FBP for 56 days. Each group contained eight replicates with ten hens per replicate. Results showed that 0.25% FBP reduced the percentage of thigh muscle, whereas 0.5% FBP reduced drip loss at 24 h post-mortem in the breast muscle compared to the control group (p < 0.05). Additionally, 0.5% FBP enhanced the total antioxidant capacity compared to the 0.25% group and increased superoxide dismutase activity compared to the control and 0.25% FBP groups (p < 0.05). In the breast muscle, 0.25 and 0.5% FBP reduced drip loss compared to the control group at 48 h post-mortem, while 0.25% FBP upregulated glutathione peroxidase 1 expression more than the other groups (p < 0.05). Network pharmacology analysis identified 302 targets related to the potential bioactive compounds in FBP and 401 targets associated with meat quality, such as core targets of insulin, protein kinase cAMP-activated catalytic subunit beta, steroid receptor coactivator, etc. The identified key signaling pathways included JAK-STAT and PI3K-Akt signaling pathways, which were related to protein synthesis and muscle growth. Molecular docking analysis confirmed strong binding activity between bioactive compounds of FBP and meat quality. In conclusion, dietary FBP supplementation enhances the breast muscle quality of spent hens through the potential bioactive compounds targeting insulin and modulating JAK-STAT and PI3K-Akt signaling pathways, without affecting carcass traits. Moreover, 0.5% FBP exhibited better effects than other treatment groups in spent hens. Full article

Ochratoxin A (OTA), a common mycotoxin contaminant, poses significant health risks through its multi-organ toxicity. While OTA is known to cause immune organ dysfunction leading to immunotoxicity, its precise mechanistic pathways remain unclear. The spleen is an important immune organ of the body and plays a key role in immune defense and homeostasis maintenance. Astaxanthin (AST), a potent antioxidant with demonstrated immunomodulatory properties, exhibits a broad therapeutic potential including anti-inflammatory, wound-healing, anti-aging, and hepatoprotective effects. Therefore, this study aimed to explore the mechanism by which AST attenuates OTA-induced immunotoxicity using a chicken OTA/AST treatment model. Sixty 1-day-old, white-feathered, sex-undifferentiated chicks were randomly allocated into four groups (n = 15): (1) Control, (2) OTA (1 mg/kg), (3) AST (100 mg/kg), and (4) OTA + AST (1 mg/kg OTA + 100 mg/kg AST). The experiment lasted for 21 days to establish the model. Subsequently, serum ELISA, antioxidant capacity assays, qRT-PCR, and western blot (WB) analyses were employed to explore the protective role of AST against immunotoxicity. The results showed that AST increased splenic organ coefficients and serum immunoglobulin (IgM and IgG) concentrations (p < 0.01) and decreased the expression of inflammatory factors (IL-8, IL-6, and IL-1β) (p < 0.01). We found that OTA was involved in the expression of the PTEN/PI3K/AKT signaling pathway (PTEN, PI3K, AKT, p-AKT (Ser473)) and apoptotic genes (Bcl-2, Bax, Caspase3, Caspase9). Notably, AST significantly attenuated OTA-induced oxidative damage (ROS, MDA, T-AOC) in the spleen (p < 0.05), upregulated the expression of PI3K and p-AKT (Ser473) (p < 0.05) and inhibited the expression of PTEN and apoptosis-related genes (p < 0.05). In summary, AST attenuates OTA-induced immunotoxicity by alleviating oxidative stress and modulating the PTEN/PI3K/AKT signaling pathway. Full article

Obesity is closely associated with the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM), primarily due to dysfunctional adipose tissue expansion and the secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β). 14-Deoxy-11,12-didehydroandrographolide (deAND), a major diterpenoid component of Andrographis paniculata, has demonstrated notable antioxidant and anti-inflammatory activities. This study aimed to investigate the protective effects and mechanisms of deAND against IL-1β-induced IR in 3T3-L1 adipocytes. Network pharmacology analysis indicated that deAND targets several IR-related signaling pathways, particularly the MAPK and IRS-1/AKT pathways. The experimental results show that IL-1β stimulated p67phox membrane translocation and reactive oxygen species (ROS) production, contributing to impaired insulin signaling by activating ERK and JNK and reducing IRS-1/AKT phosphorylation, which ultimately decreased insulin-stimulated glucose uptake. Pretreatment with deAND effectively inhibited NOX2-derived ROS generation, suppressed ERK/JNK activation, restored IRS-1/AKT phosphorylation, and reversed the reduction in glucose uptake caused by IL-1β. These findings suggest that deAND can alleviate IR by inhibiting NOX2-mediated oxidative stress, restoring insulin signaling and improving glucose uptake, highlighting its potential as a therapeutic agent for obesity-related IR. Full article

Background: A range of cancer cells are significantly inhibited by FTY720. It is unknown, nevertheless, how FTY720 influences the onset of non-small cell lung cancer (NSCLC). Using bioinformatics techniques, we analyzed and the possible molecular mechanisms and targets of FTY720 for the treatment of NSCLC. Methods: DEGs (Differentially expressed genes) were acquired by differential analysis of the dataset GSE10072. Obtained FTY720 target genes and NSCLC disease genes from databases such as Swiss-TargetPrediction and GeneCard. Subsequently, target and disease genes, as well as DEGs, were merged for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, gene ontology (GO), and protein interaction analysis. The overlapping genes of DEGs and target genes, and disease genes were also obtained separately and subjected to survival as well as expression analyses. We constructed the regulatory network of miRNAs and transcription factors (TFs) on hub genes. Finally, the immune cell association of hub genes was evaluated using the ssGSEA method, molecular docking of FTY720 to hub genes was carried out utilizing Autodock, and molecular dynamics simulations were conducted. Results: In this study, 444 DEGs, 232 target genes of FTY720, and 466 disease genes were obtained. Moreover, a total of 1062 genes were obtained by removing duplicate values after merging, among which PIK3R1, Akt1, and S1PR1 had the highest DEGREE values in the protein interactions network, and these genes were primarily enriched in MAPK, PI3K-Akt signaling pathways, with the PI3K-Akt signaling pathway being the most prominent. Among the overlapping genes, three potential targets of FTY720 for NSCLC treatment were found: S1PR1, ZEB2, and HBEGF. ZEB2 and S1PR1 were determined to be hub genes and to significantly affect NSCLC prognosis by survival analysis. Furthermore, hsa-miR-132-3p, hsa-miR-192-5p, and hsa-miR-6845-3p were strongly associated with FTY720 for the treatment of NSCLC; CTBP1 (carboxy-terminal binding protein 1), EZH2 (protein lysine N-methyltransferase), and ZNF610 (zinc-finger protein 610) may all influence the expression of ZEB2 and S1PR1. Hub genes had a substantial negative link with memory B cells and a significant positive correlation with memory CD8 T cells and Th17 helper T cells. The molecular docking and kinetic simulation results of FTY720 with the two hub genes indicate that the protein-ligand complex has good stability. Conclusion: Our research indicates that FTY720 may inhibit NSCLC via possible targets ZEB2 and S1PR1, further laying the theoretical foundation for the utilization of FTY720 in NSCLC treatment. Full article

Gardenia jasminoides J.Ellis is an important medicinal and edible resource. The fruit of Gardenia jasminoides J.Ellis contains a natural iridoid called geniposide, which has the ability to dramatically suppress the growth of a number of cancer cell lines. This work examined the impact and potential mechanism of action of geniposide on oral squamous cell carcinoma using network pharmacology, molecular docking, molecular dynamics simulation, and cellular experiments. Based on network pharmacology, 145 potential targets of geniposide in the treatment of OSCC were found. The top five core targets were selected according to the degree values of the nodes, AKT1, EGFR, SRC, HSP90AA1, and PIK3R1, which involved signaling pathways and biological processes, such as the PI3K-Akt signaling pathway, pathways in cancer, phosphorylation, and the regulation of the apoptotic process. Molecular docking showed that geniposide exhibited good binding ability with the core targets AKT1 and EGFR. Molecular dynamics simulations further confirmed the stability of the binding between geniposide and the targets. The results of cell experiments showed that the activity of HSC-3 cells was dose-dependently inhibited by geniposide, and AO/EB staining showed that geniposide was able to induce programmed apoptosis. Meanwhile, it was found that the expressions of p-EGFR, p-AKT, and Bcl-2 were downregulated in HSC-3, and the expressions of PTEN, Bax, and Caspase-3 were upregulated. Geniposide may inhibit OSCC by affecting the PI3K-Akt signaling pathway and apoptotic process by regulating the expressions of p-EGFR, p-AKT, Bcl-2, Bax, Caspase-3, and PTEN. Full article

Background: Despite advances in gene-targeted and immunotherapies, many aggressive cancers—including glioblastoma and triple-negative breast cancer—remain refractory to treatment. Mounting evidence implicates metabolic reprogramming, especially dysregulation of glucose and glutamine metabolism, as a core hallmark of tumor progression. Natural compounds with metabolic-modulatory effects have emerged as promising adjuncts in oncology. Research Question and Objectives: This review investigates the following question: How can metabolic-targeted therapies—particularly those modulating the Warburg effect and glutamine metabolism—improve cancer treatment outcomes, and what role do natural compounds play in this strategy? The objectives were to (1) evaluate the therapeutic potential of metabolic interventions targeting glucose and glutamine metabolism, (2) assess natural compounds with metabolic regulatory activity, (3) examine integration of metabolic-targeted therapies with conventional treatments, and (4) identify metabolic vulnerabilities in resistant malignancies. Methods: A qualitative systematic review (QualSR) was conducted following PRISMA guidelines. A total of 87 peer-reviewed studies published between 2000 and 2024 were included. Inclusion criteria required clearly defined mechanistic or clinical endpoints and, for clinical trials, sample sizes ≥ 30. Data extraction focused on tumor response, survival, metabolic modulation, and safety profiles. Results: Curcumin significantly reduced serum TNF-α and IL-6 (both p = 0.001) and improved antioxidant capacity (p = 0.001). EGCG downregulated ERα (p = 0.002) and upregulated tumor suppressors p53 and p21 (p = 0.001, p = 0.02). High-dose intravenous vitamin C combined with chemoradiotherapy yielded a 44.4% pathologic complete response rate in rectal cancer. Berberine suppressed Akt/mTOR signaling and glutamine transporter SLC1A5 across tumor types (q < 10⁻¹⁰). However, poor bioavailability (e.g., EGCG t½ = 3.4 ± 0.3 h) and systemic toxicity limit their standalone clinical application. Conclusions: Metabolic-targeted therapies—particularly natural compounds acting on glucose and glutamine pathways—offer a viable adjunct to standard cancer therapies. Clinical translation will require biomarker-driven patient stratification, improved delivery systems, and combination trials to optimize the therapeutic impact in treatment-resistant cancers. Full article

Efficient utilization of food industry waste supports sustainable development. Idesia polycarpa Maxim cake meal (an oil-processing by-product) is rich in bioactive flavonoids, but the refined purification, anti-non-small cell lung cancer (NSCLC) activity, and mechanism of its total flavonoids (IPTF) remain unclear—restricting high-value use. This study optimized IPTF purification via polyamide resin gradient elution and characterized its chemical composition by HPLC/LC-MS. In vitro assays assessed IPTF’s effects on A549 cell proliferation, migration, invasion, colony formation, and apoptosis; network pharmacology and molecular docking predicted mechanisms, validated via Western blotting for key signaling pathways. Results showed IPTF purity was significantly improved after purification; HPLC/LC-MS identified rutin, quercetin, and six minor components as key constituents. IPTF inhibited A549 proliferation, and network pharmacology indicated it synergistically targets the PI3K/AKT and EGFR-MAPK pathways—validated by reduced phosphorylation of p-AKT, p-EGFR, and p-ERK. This work offers a novel strategy for I. polycarpa cake meal valorization and highlights IPTF’s potential as a multi-target natural candidate for NSCLC therapy. Full article

Background: Hypertension is a leading cause of cardiovascular morbidity and mortality. Taxifolin has shown cardiovascular benefits, but its antihypertensive mechanisms remain poorly defined. This study aimed to comprehensively elucidate the molecular mechanisms underlying Taxifolin’s blood pressure-lowering effects by integrating network pharmacology, molecular docking, ex vivo functional studies, and in vivo validation. Methods: Network pharmacology and molecular docking prioritized targets. Ex vivo thoracic aortas were obtained from healthy male Sprague–Dawley (SD) rats, and rings (3–4 mm) were prepared for vasorelaxation studies. Pathway-specific inhibitors, Western blotting, and ELISA were used to investigate mechanisms. In vivo, spontaneously hypertensive rats (SHRs) received oral Taxifolin 15, 30, or 60 mg/kg once daily for 28 days; propranolol (80 mg/kg) served as the positive control. Results: Taxifolin produced robust vasorelaxation in endothelium-intact rings (Rmax ≈ 121%), falling to ~72% after denudation. Relaxation was attenuated by LY294002, ODQ, indomethacin, and glibenclamide. In SHR aorta, Taxifolin increased NO by ~132% and cGMP by ~1.9-fold and upregulated p-Akt and eNOS; LY294002 abolished these effects. In vivo, Taxifolin reduced systolic blood pressure by ≈60 mmHg without adverse changes in hematology, biochemistry, or body weight. Conclusions: Taxifolin lowers blood pressure through multiple vascular mechanisms consistent with PI3K/Akt/eNOS, NO–sGC–cGMP, COX-2/PGI₂ and calcium-handling pathways, supporting its potential as a safe antihypertensive candidate. Full article

Background: Acute myeloid leukemia (AML) remains a hematopoietic clonal malignancy that is characterized by a poor prognosis, largely attributable to chemotherapy resistance and a high incidence of post-chemotherapy relapse. Therefore, the identification of novel molecular markers is crucial for optimizing treatment regimens and improving outcomes for this disease. Methods: We first investigated the expression levels of poly(ADP-ribose)polymerase 3(PARP3) mRNA in data from our center and the Gene Expression Omnibus (GEO), then explored the role of PARP3 in AML through cell experiments. Results: Our results demonstrated that the expression levels of PARP3 were significantly elevated in AML samples compared to controls (p < 0.05). Based on the median expression of PARP3, 151 cases of AML from TCGA data were divided into two groups. The results showed that PARP3-high group had markedly shorter overall survival (OS) than the PARP3-low group (OS: median: 1.18 vs. 3.88 years; p < 0.001). The overexpression of PARP3 was correlated with older age and high-risk stratification in the AML from TCGA data (p < 0.05). Finally, we confirmed that specifically down-regulating PARP3 expression impaired AML cell proliferation, disrupted cell cycle process, inhibited migration, accelerated apoptosis, and impaired the PI3K/AKT/mTOR signaling pathway in vitro. Conclusions: PARP3-mediated activation of the PI3K/AKT/mTOR signaling pathway enhances AML cell proliferation and migration, identifying it as a potential therapeutic target for poor-prognosis AML. Full article

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is essential for physiological processes such as development and wound healing, but its dysregulation contributes to a range of pathological conditions including cancer, diabetic retinopathy, and chronic inflammation. In recent years, marine-derived compounds have emerged as promising multitarget agents with anti-angiogenic potential. Posidonia oceanica, a Mediterranean seagrass traditionally used in folk medicine, is increasingly recognized for its pharmacological properties, including antioxidant, anti-inflammatory, and anti-invasive activities. This study investigated the effects of a hydroethanolic extract from P. oceanica leaves (POE) on human Endothelial Colony-Forming Cells (ECFCs), a subpopulation of endothelial progenitor cells with high proliferative and vessel-forming capacity, and a relevant model for studying pathological angiogenesis. ECFCs were treated with POE (4–8 µg/mL), and cell viability, morphology, migration, invasion, tube formation, oxidative stress, and activation markers were evaluated. POE did not alter ECFC morphology or viability, as confirmed by Trypan Blue and MTT assays. However, functional assays revealed that POE significantly impaired ECFC migration, invasion, and in vitro angiogenesis in a dose-dependent manner. Under VEGF (Vascular endothelial growth factor) stimulation, POE reduced intracellular ROS accumulation and downregulated key redox-regulating genes (hTRX1, hTRX2, PRDX2, AKR1C1, AKR1B10). Western blot analysis showed that POE inhibited VEGF-induced phosphorylation of KDR, mTOR and p-ERK, while p-AKT remained elevated, indicating selective disruption of VEGF downstream signaling. Furthermore, POE reduced the expression of pro-inflammatory and pro-coagulant markers (VCAM-1, ICAM-1, TF) and partially reversed TNF-α–induced endothelial activation. These findings suggest that POE exerts anti-angiogenic effects through a multitargeted mechanism, supporting its potential as a natural therapeutic agent for diseases characterized by aberrant angiogenesis. Full article