Search Results (370)

Background and Objectives: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening vascular disease with limited effective diagnostic and therapeutic strategies. Although endothelial barrier dysfunction represents an early event in TAAD pathogenesis, the role of endothelial tight junction proteins remains largely undefined. In this study, we systematically explored the function of claudin-5 (CLDN5), an endothelial-specific tight junction sealing protein, in TAAD through integrated bioinformatic, clinical, and experimental approaches. Materials and Methods: In the study, we combined bioinformatic analysis of the CLDN5 gene with clinical and cellular investigations. The clinical cohort included 44 patients with thoracic aortic dissection (TAAD) and 41 healthy controls. Plasma CLDN5 levels were measured by ELISA. Cellular studies involved treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α) and performing CLDN5 knockdown, with barrier function assessed using transendothelial electrical resistance and permeability assays. Results: Plasma CLDN5 was significantly elevated in TAAD patients (14.20 ± 1.394 ng/mL) compared to controls (6.061 ± 0.8208 ng/mL, p < 0.05) and showed strong diagnostic potential with an area under the receiver operating characteristic curve (AUC) of 0.7877 (95% CI: 0.6897–0.8857). In cellular experiments, TNF-α treatment induced the release of CLDN5 fragments into the supernatant and reduced membrane CLDN5. Furthermore, CLDN5 knockdown directly impaired endothelial barrier function. Conclusions: Our findings identify CLDN5 as a promising circulating biomarker for TAAD diagnosis and provide new insights into TAAD pathogenesis, offering potential diagnostic strategies. Full article

Microvascular leakage is an early hallmark of diabetic retinopathy (DR), but the redox-dependent mechanisms underlying this dysfunction remain unclear. Here, we investigated whether p38α mitogen-activated protein kinase (MAPK) activates transglutaminase 2 (TGase2) through reactive oxygen species (ROS) generation, thereby promoting hyperglycemia-induced vascular permeability in diabetic retinas. In human retinal endothelial cells (HRECs), vascular endothelial growth factor (VEGF), which is elevated under hyperglycemic conditions, activated both p38α MAPK and TGase2. VEGF-induced TGase2 activation was inhibited by the p38 MAPK inhibitor SB203580 or by p38α MAPK siRNA. Similarly, VEGF-stimulated TGase2 activity in non-diabetic mouse retinas was blocked by knockdown of either p38α MAPK or TGase2. In diabetic retinas, hyperglycemia-increased ROS production and TGase2 activity were reduced by SB203580 or p38α MAPK siRNA, but not by the TGase inhibitor cystamine, indicating upstream ROS-dependent regulation. The antioxidant Trolox also suppressed TGase2 activation in VEGF-treated HRECs and diabetic retinas. Functionally, knockdown of p38α MAPK or TGase2 preserved vascular endothelial (VE)-cadherin integrity and attenuated cytoskeletal remodeling in HRECs and diabetic retinas, resulting in reduced microvascular leakage. These findings identify a redox-dependent p38α MAPK–TGase2 axis as a key mediator of retinal vascular permeability in DR and highlight this pathway as a potential therapeutic target for maintaining vascular integrity. Full article

Endothelial cell (EC) barrier integrity is tightly regulated by the activity of the non-muscle myosin light chain kinase (nmMLCK) under diverse pathological inflammatory conditions (pneumonia, sepsis) and exposure to mechanical stress. Inflammatory stimuli, including lipopolysaccharide (LPS), cytokines, and damage-associated molecular patterns (DAMPs), increase EC permeability through nmMLCK-dependent EC paracellular gap formation. However, the exact mechanisms by which nmMLCK regulates vascular barrier dysfunction in acute lung injury (ALI) remain incompletely understood. We hypothesized that inflammation-induced ROS results in the peroxynitrite-mediated nitration of nmMLCK that contributes to EC barrier disruption. Human lung EC exposure to either the peroxynitrite donor, SIN-1, or to LPS, triggered significant nmMLCK nitration, which was abolished by the oxidant scavenger, MnTMPyP. Mass spectrometry of SIN-1-treated nmMLCK identified multiple nitrated tyrosines. Nitration of Y1410 proved a critical PTM as site-directed substitution with alanine (Y1410A) abolished both SIN-1- and LPS-induced nmMLCK nitration. nmMLCK nitration disrupts wild-type nmMLCK interaction with Kindlin-2, a cytoskeletal regulator of vascular barrier stability, whereas EC transfected with the Y1410A nmMLCK mutant exhibited preserved Kindlin-2 binding, reflected by alterations in trans-EC electrical resistance (TEER). Consistent with these observations, LPS-challenged murine lungs displayed enhanced nmMLCK nitration and diminished nmMLCK-Kindlin-2 association. Functionally, SIN-1 markedly impaired EC barrier integrity (TEER), which was not observed in ECs expressing the Y1410A mutant. Together, these findings suggest that nmMLCK nitration at Y1410 is a critical molecular mechanism contributing to vascular leakage, highlighting this modification as a potential therapeutic target to reduce inflammation-induced vascular permeability. Given nmMLCK’s established role in barrier regulation, we hypothesized that LPS-induced peroxynitrite formation may promote the nitration of nmMLCK tyrosine residues: a PTM that potentially contribute to nmMLCK’s regulation of EC barrier integrity. Full article

Background: Refractory ulcerative colitis (rUC) represents a critical therapeutic challenge, with emerging evidence implicating gut vascular barrier (GVB) dysfunction in disease persistence. We investigated whether dysregulation of the endothelial BMP9-ALK1 signaling axis—a pathway not previously studied in UC—is associated with GVB impairment and treatment resistance, and explored its therapeutic potential. Methods: Serum BMP9 and mucosal ALK1 levels were compared across rUC, non-rUC, and healthy cohorts. The therapeutic efficacy of BMP9 was evaluated in DSS-induced murine colitis by examining vascular permeability, histopathology, and inflammatory markers, while mechanistic roles were investigated using human intestinal microvascular endothelial cells. Results: Serum BMP9 levels were significantly reduced in rUC versus non-rUC patients, inversely correlating with post-treatment disease severity (Modified Mayo Score: r = −0.471, 95% CI: −0.618 to −0.293, p < 0.001; UCEIS: r = −0.495, 95% CI: −0.637 to −0.321, p < 0.001). Stratified analyses confirmed that BMP9 deficiency was associated with treatment-refractory status independent of baseline disease severity. Intestinal ALK1 was downregulated in rUC mucosa. In murine DSS-colitis, BMP9 attenuated disease severity, colon shortening, histopathological damage, inflammatory cytokines, and early pro-fibrotic markers (Col1a1, Col3a1, α-SMA). BMP9 activated SMAD1, restored VE-cadherin, and reduced hyperpermeability (FITC-dextran leakage decreased from 10.2-fold to 2.1-fold, p < 0.001). In vitro, BMP9 inhibited TNF-α-induced neutrophil migration and enhanced endothelial tube stability via ALK1. Conclusions: Dysregulated BMP9-ALK1 signaling may contribute to GVB dysfunction in UC. BMP9 supplementation attenuates vascular leakage and inflammation in experimental colitis, identifying a potential therapeutic target warranting further investigation. Full article

Background/Objectives: Cerebral angiography is a cornerstone diagnostic and therapeutic procedure for cerebrovascular diseases; however, its potential effects on vascular integrity and cellular homeostasis remain incompletely elucidated. This systematic review aims to comprehensively evaluate endothelial and histopathological alterations induced by cerebral angiographic procedures, with particular emphasis on oxidative stress, inflammation, endothelial dysfunction, and blood–brain barrier disruption. Methods: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science databases were systematically searched for studies published between 1981 and 2025 using predefined keywords related to cerebral angiography, endothelial injury, oxidative stress, inflammation, and histopathological changes. A total of 1142 records were identified, and 216 duplicates were removed. Following title and abstract screening, 312 full-text articles were assessed for eligibility, of which 112 were excluded due to irrelevance or insufficient endothelial or histopathological data. Ultimately, 200 studies were included in the qualitative synthesis. The literature identification, screening, and selection process are summarized in the manuscript. The review protocol was not prospectively registered. Results: The included studies demonstrated that cerebral angiographic procedures induce endothelial and microvascular alterations through both mechanical and contrast-mediated mechanisms. Iodinated contrast agents were consistently associated with increased reactive oxygen species production, reduced endothelial nitric oxide bioavailability, mitochondrial dysfunction, and activation of pro-inflammatory signaling pathways, including nuclear factor kappa B (NF-κB). Histopathological findings revealed endothelial swelling, vacuolization, apoptosis, microthrombus formation, inflammatory cell infiltration, and disruption of endothelial junctions, leading to increased vascular permeability and blood–brain barrier impairment. Mechanical factors related to catheter manipulation and high-pressure contrast injection further exacerbated endothelial injury by altering shear stress and promoting leukocyte adhesion. The severity of endothelial damage and inflammatory responses was consistently greater in patients with comorbid conditions such as diabetes mellitus, hypertension, and atherosclerotic disease. Conclusions: Cerebral angiography may induce endothelial dysfunction and histopathological vascular injury predominantly through oxidative and inflammatory mechanisms. Optimization of contrast agent selection, refinement of procedural techniques, and implementation of endothelial-protective strategies may mitigate vascular injury and improve procedural safety. Further translational and clinical studies are warranted to identify biomarkers and protective interventions targeting angiography-induced endothelial damage. Full article

Proteoglycans are macromolecules consisting of a core protein and one or more glycosaminoglycan side chains. Proteoglycans synthesized by vascular endothelial cells modulate various functions such as anticoagulant activity and vascular permeability. We previously reported that some heavy metals interfere with proteoglycan expression, and that organic–inorganic hybrid molecules, such as metal complexes and organometallic compounds, serve as useful tools to analyze proteoglycan synthesis mechanisms. However, the effects of metal compounds lacking electrophilicity on proteoglycan synthesis remain unclear. Au₂₅(SG)₁₈, a nanoscale gold cluster consisting of a metal core protected by gold–glutathione complexes, exhibits extremely low intramolecular polarity. In this study, we investigated the effect of Au₂₅(SG)₁₈ on proteoglycan synthesis in vascular endothelial cells. Au₂₅(SG)₁₈ accumulated significantly in vascular endothelial cells at low cell density and suppressed the expression of perlecan, a major heparan sulfate proteoglycan in cells, by inactivating ADP-ribosylation factor 6 (Arf6). Additionally, Au₂₅(SG)₁₈ reduced the expression of biglycan, a small dermatan sulfate proteoglycan, in vascular endothelial cells at low cell density; however, the underlying mechanisms remain unclear. Overall, our findings suggest that organic–inorganic hybrid molecules regulate the activity of Arf6-mediated protein transport to the extracellular space and that perlecan is regulated through this mechanism, highlighting the importance of Arf6-mediated extracellular transport for maintaining vascular homeostasis. Full article

Background/Objectives: Neovascularization, defined as the sprouting of new blood vessels from pre-existing vasculature, is a critical pathological feature in ocular diseases such as pathological myopia and represents a leading cause of corneal vision loss. Vascular endothelial growth factor A (VEGFA) plays a pivotal role in endothelial cell proliferation, migration, survival by anti-apoptotic signaling, and vascular permeability. Dysregulation of VEGFA is closely linked to pathological neovascularization. Exosomes, nanosized phospholipid bilayer vesicles ranging from 30 to 150 nm, have emerged as promising gene delivery vehicles due to their intrinsic low immunogenicity, superior cellular uptake, and enhanced in vivo stability. This study aimed to investigate whether highly purified mesenchymal stem cell (MSC)-derived exosomes loaded with VEGFA siRNA labeled with FAM can effectively suppress pathological corneal neovascularization (CNV) via targeeted cellular transduction and VEGFA inhibition. Furthermore, we examined whether the therapeutic effect involves the modulation of the PI3K–Akt–Caspase-3 signaling axis. Methods: Exosomes purified by chromatography were characterized by electronmicroscopy, standard marker immunoblotting, and nanoparticle tracking analysis. In vitro, we assessed exosome uptake and cytoplasmic release, suppression of VEGFA mRNA/protein, cell viability, and apoptosis. In a mouse CNV model, we evaluated tissue reach and stromal retention after repeated intrastromal injections; anterior segment angiogenic indices; CD31/VEGFA immunofluorescence/immunoblotting; phosphorylated PI3K and Akt; cleaved caspase-3; histology (H&E); and systemic safety (liver, kidney, and spleen). Results: Exosomes were of high quality and showed peak efficacy at 48 h, with decreased VEGFA mRNA/protein, reduced viability, and increased apoptosis in vitro. In vivo, efficient delivery and stromal retention were observed, with accelerated inhibition of neovascularization after Day 14 and maximal effect on Days 17–19. Treatment reduced CD31 and VEGFA, decreased p-PI3K and p-Akt, and increased cleaved caspase-3. Histologically, concurrent reductions in neovascularization, inflammatory cell infiltration, and inflammatory epithelial thickening were observed, alongside a favorable systemic safety profile. Conclusions:VEGFA siRNA-loaded exosomes effectively reduce pathological CNV via a causal sequence of intracellular uptake, cytoplasmic release, targeted inhibition, and phenotypic suppression. Supported by consistent PI3K–Akt inhibition and caspase-3–mediated apoptosis induction, these exosomes represent a promising local gene therapy that can complement existing antibody-based treatments. Full article

As a natural flavonoid, the flavonoid luteolin is characterized by its powerful antioxidant and anti-inflammatory effects. While its precise mechanisms require further elucidation, existing evidence confirms its efficacy in ameliorating myocardial ischemia–reperfusion injury (MIRI). This research was designed to investigate the mechanism through which luteolin protects against MIRI. We established MIRI rat models through the ligation of left anterior descending coronary artery (LAD). To evaluate the cardioprotective effects of luteolin, echocardiographic analysis was performed, Hematoxylin and Eosin (HE) staining, and serum cardiac injury markers creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Cardiac vascular permeability was determined using Evans blue staining. To mimic ischemia–reperfusion injury, endothelial cells (ECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Endothelial cell barrier function was evaluated through F-actin phalloidin staining and FITC-Dextran fluorescence leakage experiments. To elucidate the molecular mechanism, FOXP1 small interfering RNA (siRNA) and NLRP3 inhibitor MCC950 were administered. In MIRI rats, luteolin significantly improved cardiac function and preserved endothelial barrier integrity. These effects were associated with upregulation of FOXP1 and suppression of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. In OGD/R-treated endothelial cells, luteolin restored barrier function and cell viability. The protective effects of luteolin were abolished after FOXP1 silencing. Pharmacological NLRP3 inhibition (MCC950) mirrored luteolin’s protection. Our study indicates that luteolin enhances endothelial barrier function and attenuates MIRI via the FOXP1-NLRP3 pathway. The current study provides a potential drug for MIRI treatment. Full article

More than 30% of diabetic patients develop dermatopathies linked to inflammation and increased vascular permeability. Considering the role of the renin–angiotensin–aldosterone system (RAAS) in diabetic complications, this study examined whether aldosterone (ALDO) and the mineralocorticoid receptor (MR) contribute to diabetes-related skin microangiopathy. Vascular permeability was measured in normoglycemic rats and insulin-dependent (streptozotocin-induced) diabetic rats. The expression of MR, 11β-hydroxysteroid dehydrogenase type 2 (HSD11β2), vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), and the tight junction protein ZO-1 was determined by PCR and immunohistochemistry. Diabetic rats received the MR antagonist eplerenone (EPL, 100 mg/kg) for 10 days. Additionally, the effects of ALDO and EPL on endothelial permeability were evaluated in human dermal microvascular endothelial cells (HMEC-1) using a Transwell system. Diabetic rats showed skin atrophy, collagen damage, elevated ALDO levels, reduced MR and HSD11β2 expression, and increased vascular permeability, along with upregulation of VEGF and vWF. EPL markedly reduced these abnormalities. In vitro, ALDO increased endothelial permeability under hyperglycemia, and EPL counteracted this effect. These findings indicate that activation of the ALDO/MR pathway promotes skin vascular permeability in diabetes through VEGF- and vWF-dependent mechanisms. MR blockade limits these changes, suggesting therapeutic potential in preventing diabetes-associated skin complications. Full article

Hypertension (HTN) and intestinal permeability (IP) are increasingly recognized as interrelated processes driven by shared oxidative and inflammatory mechanisms. This review synthesizes evidence linking HTN-induced vascular dysfunction to alterations in intestinal barrier integrity and explores the potential of dietary flavonoids as modulators of these pathologies. A narrative approach was used to synthesize findings from cellular, animal, and human studies that specifically address how flavonoids influence the molecular pathway connecting HTN and IP. Emerging evidence suggests that HTN-driven vascular injury, which is characterized by reduced nitric oxide bioavailability, increased reactive oxygen species, and pro-inflammatory signaling, contributes to tight junction disruption and increased IP. Mechanistic evidence indicates that flavonoids exert both direct antioxidant effects and indirect actions via the modulation of key cellular pathways. Preclinical and clinical data demonstrate that flavonoid-rich foods and isolated compounds can lower blood pressure, enhance endothelial function, and preserve intestinal barrier integrity by stabilizing tight junction proteins and attenuating pro-inflammatory signaling. Together, these findings highlight flavonoids as cross-system modulators that may mitigate HTN-associated increases in IP. Further research addressing sex, race, and age differences, as well as flavonoid bioavailability and dose optimization, is needed to clarify their translational potential. Full article

Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants’ in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial–mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28–42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment. Full article

Ischemic stroke remains one of the most catastrophic diseases in neurology, in which, due to a disturbance in the cerebral blood flow, the brain is acutely deprived of its oxygen and glucose oligomer, which in turn rapidly leads to energetic collapse and progressive cellular death. There is now increasing evidence that this type of stroke is not simply a type of ‘oxidative stress’ but rather a programmable loss-of-redox homeostasis, within which electron flow and the balance of oxidants/reductants are cumulatively displaced at the level of the single molecule and at the level of the cellular area. The advances being made in cryo-electron microscopy, lipidomics, and spatial omics are coupled with the introduction of a redox code produced by the interaction of the couples NADH/NAD⁺, NADPH/NADP⁺, GSH/GSSG, BH₄/BH₂, and NO/SNO, which determine the end results of the fates of the neurons, glia, endothelium, and pericytes. Within the mitochondria, pathophysiological events, including reverse electron transport, succinate overflow, and permeability transition, are found to be the first events after reperfusion, while signals intercommunicating via ER–mitochondria contact, peroxisomes, and nanotunnels control injury propagation. At the level of the tissue, events such as the constriction of the pericytes, the degradation of the glycocalyx, and the formation of neutrophil extracellular traps underlie microvascular failure (at least), despite the effective recanalization of the vessels. Systemic influences such as microbiome products, oxidized lipids, and free mitochondrial DNA in cells determine the redox imbalance, but this generally occurs outside the brain. We aim to synthesize how the progressive stages of ischemic injury evolve from the cessation of flow to the collapse of the cell structure. Within seconds of injury, there is reverse electron transport (RET) through mitochondrial complex I, with bursts of superoxide (O₂•⁻) and hydrogen peroxide (H₂O₂) being produced, which depletes the stores of superoxide dismutase, catalase, and glutathione peroxidase. Accumulated succinate and iron-induced lipid peroxidation trigger ferroptosis, while xanthine oxidase and NOX2/NOX4, as well as uncoupled eNOS/nNOS, lead to oxidative and nitrosative stress. These cascades compromise the function of neuronal mitochondria, the glial antioxidant capacity, and endothelial–pericyte integrity, leading to the degradation of the glycocalyx with microvascular constriction. Stroke, therefore, represents a continuum of redox disequilibrium, a coordinated biochemical failure linking the mitochondrial metabolism with membrane integrity and vascular homeostasis. Full article

This review reappraises the anti-inflammatory potential of the contact activation system (CAS) in intensive care through an evolutionary lens. The authors propose that coagulation factor XII (FXII) and related components evolved in terrestrial animals as a “foreign-surface sensing–immunothrombosis” module, helping to explain the minimal bleeding phenotype of FXII deficiency and the secondary loss of F12 in marine mammals. CAS shares components with the kallikrein–kinin system (KKS): alpha-coagulation factor XIIa (α-FXIIa) drives coagulation factor XI (FXI) activation to amplify coagulation, whereas betacoagulation factor XIIa (β-FXIIa) activates the KKS to generate bradykinin, promoting vasodilation and vascular leak. Beyond proteolysis, zymogen FXII signals via urokinase-type plasminogen activator receptor (uPAR) to induce neutrophil extracellular trap formation (NETosis), thereby amplifying immunothrombosis. Clinically, the relevance spans sepsis and extracorporeal organ support: pathogens can hijack CAS/KKS to facilitate invasion, and artificial surfaces such as extracorporeal membrane oxygenation (ECMO) circuits chronically trigger contact activation. In animal models, selective inhibition of FXII/FXI prolongs circuit life and attenuates pulmonary edema and inflammation without materially increasing bleeding. The review also catalogs “non-coagulation” roles of CAS members: Activated coagulation factor XI (FXIa) modulates endothelial permeability and smooth-muscle migration, and the FXII heavy chain exhibits direct antimicrobial activity—underscoring CAS as a nexus for coagulation, inflammation, and host defense. Overall, CAS inhibitors may couple “safe anticoagulation” with “cascade-level anti-inflammation,” offering a testable translational path for organ protection in the ICU alongside infection control and informing combined, precision strategies for anticoagulation and anti-inflammatory therapy. Full article

The endothelium, once considered merely a vascular lining responsible for selective permeability to water and electrolytes, is now recognised as a key regulator of vascular tone through the release of mediators such as oxylipins, nitric oxide, and hyperpolarizing factors. This in vitro study investigated the biological activity of Vesvein, a natural formulation containing Diosmin/Hesperidin, Ruscus aculeatus, Bromelain, and Ananas comosus, on intestinal and endothelial cells. Vesvein enhanced intestinal cell viability and preserved barrier integrity, as demonstrated by increased tight junction expression at both single and double concentrations. In endothelial cells, the compound improved parameters linked to venous insufficiency, elevating nitric oxide production by approximately 1.39-fold at a single dose and 1.65-fold at a double dose. These findings indicate a potential role for Vesvein in supporting endothelial health and vascular function in vitro. Preliminary evidence from intestinal models further suggests preserved barrier properties, which may positively influence absorption and bioavailability, thereby enhancing its vascular benefits. Full article

Peripheral edema is a pathological condition caused by abnormal fluid accumulation in the interstitial space due to elevated vascular permeability and inflammation. This study evaluated the therapeutic efficacy of Terminalia chebula fruit extract (TCE) in inflammation-induced peripheral edema and clarified its molecular mechanisms. Using hydrogen peroxide (H₂O₂)-stimulated human umbilical vein endothelial cells (HUVECs), TCE was tested for effects on cell viability, inflammatory gene expression, intracellular reactive oxygen species, endothelial barrier integrity, and vascular endothelial growth factor (VEGF)-induced migration. Its influence on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling was examined. In vivo, TCE was assessed in acetic acid-induced peritoneal vascular permeability and carrageenan-induced paw edema models, followed by histological analysis and serum tumor necrosis factor-α (TNF-α) measurement. TCE restored cell viability (76.2% to 94.8%), reduced TNF, IL6, and PTGS2 mRNA expression, and decreased reactive oxygen species by 27.2%. It enhanced barrier integrity, increased transendothelial electrical resistance, and inhibited VEGF-induced migration. TCE suppressed NF-κB and MAPK activation. In vivo, TCE reduced Evans blue extravasation by 41.6% and paw edema by 67.5%. Histology showed reduced dermal thickening and inflammatory infiltration, and serum TNF-α levels were lowered. TCE attenuates peripheral edema by preserving endothelial barrier function and suppressing inflammatory signaling, supporting its potential as a therapeutic agent for inflammation-associated vascular dysfunction and edema. Full article